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Spotlight on Drug Pipeline: 2019 and Beyond Michele Yoon, Pharm.D. 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 1 Ventegra Overview Formed in 2004 “Veritas” (Truth) + “Integritas” (Integrity) Company of Healthcare Professionals! A family-owned California Corporation Based in Glendale, CA Certified Small Business Certified B-Corp. (by B-Lab) Certified Member of MSDC Ventegra, Inc., a California Benefit Corporation Servicing 107 Clients; 9,805,193 lives (4Q 2015) Being recognized as a “new Class of Trade” 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 2 1 Overview • Key trends • Pipeline targets most impactful to physician groups • Specialty drugs • Significant pipeline therapeutic areas • Management strategies 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 3 Market Trends 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 4 2 2018 FDA approvals: All-time Record • 61 new molecular entities approved • 1996 was previous record @ 50 https://www.forbes.com/sites/bernardmunos/2019/01/14/2018-new-drugs-approvals-an-all-time-record-and-a-watershed/#4fbcb80a332d 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 5 Rare Diseases = 51% of Approvals https://www.forbes.com/sites/bernardmunos/2019/01/14/2018-new-drugs-approvals-an-all-time-record-and-a-watershed/#4fbcb80a332d 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 6 3 Trends https://www.forbes.com/sites/bernardmunos/2019/01/14/2018-new-drugs-approvals-an-all-time-record-and-a-watershed/#4fbcb80a332d 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 7 • An orphan drug is a product intended for the treatment, diagnosis, or prevention of a rare disease. A rare disease also affects fewer than 200,000 people in the United States 2017-2018 Pharmaceutical Marketplace Trends: Douglas Long, V.P. Industry Relations, IQVIA. Market Trends and Pricing 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 8 4 2017-2018 Pharmaceutical Marketplace Trends: Douglas Long, V.P. Industry Relations, IQVIA. Market Trends and Pricing 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 9 Trends 2019 • Specialty drugs will continue to dominate the new drug approvals • Specialty drugs will attribute to approx. 50% of the prescription spend by 2020 • 2024: Orphan drug pipeline will contribute $188bn in sales (35% of combined pipeline forecast) • Increased competition • Some specialty blockbusters are coming to end of their exclusivity • Potential for generic and biosimilar competition • Caner drug development • Orphan drug development • Top therapeutic areas : Blood, CNS and respiratory AMCP Annual Meeting March 26, 2019. [P1] Specialty Pharmaceuticals in Development. Aimee Theraldson, Pharm.D. Accessed 5/9/19 www.evaluate.com/orphandrug2019. Accessed 5/9/19 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 10 5 Therapy Classes Impacted by Specialty Significant Disease Impacted by Specialty Drugs Cancer* HIV/AIDS* Crohn’s Disease Immune disorders* Gaucher’s Disease Infertility Growth Hormone Deficiency Multiple Sclerosis* Hemophilia* Pulmonary hypertension Hepatitis C* Rheumatoid Arthritis* *Indicates therapeutic class with maturing products 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 11 Increased Competition AMCP Annual Meeting March 26, 2019. [P1] Specialty Pharmaceuticals in Development. Aimee Theraldson, Pharm.D. Accessed 5/9/19 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 12 6 AMCP Annual Meeting March 26, 2019. [P1] Specialty Pharmaceuticals in Development. Aimee Theraldson, Pharm.D. Accessed 5/9/19 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 13 Biosimilar* Opportunity *FDA BIOSIMILAR definition: Biologic product that is “highly similar to” an approved biologic product (the “reference,” “originator,” or “bio- originator” product) and that has “no clinically meaningful differences” in safety or effectiveness as compared to the reference product AMCP Annual Meeting March 26, 2019. [P1] Specialty Pharmaceuticals in Development. Aimee Theraldson, Pharm.D. Accessed 5/9/19 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 14 7 FDA-Approved Biosimilars Approval Biosimilar Originator Launch Biologic Date 9/23/16 Amjevita – Amgen/Adalimumab-atto Humira® 2023 8/25/17 Cyltezo - Boehringer/Adalimumab-adbm 2023 10/31/18 Hyrimoz – Sandoz/Adalimumab-adaz 2023 9/14/17 Mvasi – Amgen/Allergan/Bevacizumab-awwb Avastin® ? 5/15/18 Retacrit – Pfizer/Epoetin alpha-epbx Procrit®/Epogen® Available 3/6/15 Erelzi – Sandoz/Etanercept-szzs Enbrel® 2019 or 2029 4/26/19 Enticovo – Samsung Bioepis/etanercept-ykro Enbrel® 2019 or 2029 3/6/15 Zarxio – Sandoz/Filgrastim-sndz Neupogen® available 7/23/18 Nivestym – Pfizer/Filgrastim-aafi available 4/5/16 Inflectra – Pfizer/Infliximab-dyyb Remicade® available 4/21/17 Renflexis – Merck/Infliximab-abda available 12/13/17 Ixifi – Pfizer/Infliximab-qbtx Not launching 6/5/18 Fulphila – Mylan/Pegfilgrastim-jmbd Neulasta® Available 11/2/18 Udenyca – Coherus/Pegfilgrastim-cbqv Available 11/28/18 Truxima – Celltrion/rituximab-abbs Rituxan ? 12/1/17 Ogivri - Mylan/trastuzumab-dkst Herceptin TBD 12/18/19 Herzuma – Celltrion/trastuzumab-pkub) 1/18/19 Ontruzant – Samsung/trastuzumab-dttb 3/12/19 Tranzimera – Pfizer/trastuzumab-qyyp 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 15 Biosimilars Pending FDA Approval as of February 2019 Biosimilar Biosimilar applicant Reference Status/Anticipated Approval Manufacturer Adalimumab Samsung Humira® – AbbVie July 2019 (Imraldi™) Bioepis/Merck Adalimumab-ADBM Pfizer Humira® - Abbvie 4Qtr2019 Bevacizumab Pfizer Avastin® - Genentech June 2019 Infliximab Amgen Remicade® – Janssen Oct. 17, 2019 Filgrastim Tanvex BioPharma Neupogen® (Amgen) Aug. 1, 2019 Filgrastim Adello Biologic Neupogen® (Amgen) 2019 - pending Filgrastim Grastoil/Apotex Neupogen® (Amgen) 2019 Pegfilgrastim Sandoz Neulasta® (pegfilgrastim) Oct. 3, 2019 Amgen Pegfilgrastim Apotex/Intas Neulasta® (pegfilgrastim) Pending (Lapelga™) Amgen Rituximab Pfizer Rituxan® (Genentech) July 2019 Trastuzumab Amgen, Allergan Herceptin® (Genentech) June 2019 (kanjinti™) Trastuzumab Pfizer Herceptin® (Genentech) 1Q:2019 (Trazimera™) Teriparatide Pfenex Forteo® (Eli Lilly) Oct. 7, 2019 https://www.jdsupra.com/legalnews/biosimilars-2018-year-in-review-72247/. accessed 2/4/19 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 16 8 Biosimilars Phase 3/Pre-BLA Biosimilar Biosimilar Reference Status/Anticipated Approval applicant Manufacturer Adalimumab Coherus Humira® – AbbVie TBD Adalimumab Fresenius Humira® - Abbvie TBD Adalimumab Kyowa Hakko Kirin Humira® - Abbvie TBD Adalimumab Momenta Humira® - Abbvie TBD Adalimumab Mylan Humira® - Abbvie TBD Aflibercept (CHS- Coherus Eyelea® – Regeneron Phase 3/BLA end of 2019. Abbvie 1420) agreement – launch 2023 Aflibercept (M710) Momenta/Mylan Eyelea® – Regeneron Phase 3 Bevacizumab Samsung Bioepis Avastin® – Genentech Phase 3 Ranibizumab Coherus Lucentis® - Genentech Phase 3 Ranibizumab Samsung Lucentis® - Genentech Phase 3 Ranibizumab Xbrane Lucentis® -Genentech Phase 3 https://www.jdsupra.com/legalnews/biosimilars-2018-year-in-review-72247/. accessed 2/4/19 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 17 Specialty Pipeline: Inflammatory/Immune Conditions Drug Manufacturer MOA Indication Route Approval (PDUFA) Risankizumab Abbvie IL-23 inhibitor Psoriasis SC Q12 wks Approved (Skyrizi®) Upadacitinib Abbvie JAK1 inhibitor RA, Crohn’s, Oral 8/20/2019 Atopic Once daily dermatitis Filgotinib Gilead JAK1 inhibitor RA Oral 2020 Once daily Bimekizumab UCB IL-17A and IL-17F Psoriasis SC Q 4wks 2020 Inhibitor Viaskin Peanut DBV Tech Allergy peanut allergy Patch TBD immunotherapy AR101 Aimmune Immunotherapy Peanut Allergy Oral 2020 https://biopharmcatalyst.com/calendars/fda-calendar. Accessed 3/15/19 AMCP Annual Meeting March 26, 2019. [P1] Specialty Pharmaceuticals in Development. Aimee Theraldson, Pharm.D. Accessed 5/9/19 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 18 9 Specialty Pipeline: Multiple Sclerosis Drug Manuf. MOA Indication Route Approval (PDUFA) Cladribine EMD Serono DNA synthesis RMS Oral Approved (Mavenclad®) inhibitor Siponimod Novartis SP1 receptor RMS, SPMS Oral Approved (Mayzent®) Diroximel Biogen/Alkermes NrF2 activator RMS Oral 10/17/19 fumarate (Vumerity™) Ozanimod Celgene SP1 – 1/5 receptors RMS Oral 3/25/20 Monomethyl Banner Life Sciences NrF2 activator RMS Oral 6/20/20 fumarate* RMS = Relapsing multiple sclerosis; SPMS = Secondary progressive multiple sclerosis *Novel fumarate bioequivalent to Tecfidera SIP = Sphingosine-1-phosphate receptor https://biopharmcatalyst.com/calendars/fda-calendar. Accessed 3/15/19 AMCP Annual Meeting March 26, 2019. [P1] Specialty Pharmaceuticals in Development. Aimee Theraldson, Pharm.D. Accessed 5/9/19 5/15/19 CONFIDENTIAL & PROPRIETARY, Ventegra, Inc. 19 Specialty pipeline: Cancer 2019 Drug Manuf. MOA Indication Route Approval (PDUFA) Erdafitinib Janssen Fibroblast growth Urothelial Cancer Oral Approved factor receptor(FGFR) inhibitor Quizartinib Daiichi Sankyo FMS-like tyrosine Acute myeloid Oral 5/25/19 kinase 3 (FTL3) leukemia inhibitor Selinexor Karyopharm Selective inhibitor Penta-refractory Oral 7/6/19 nuclear export (SINE) multiple myeloma after 3 prior txs Pexidartinib Daiichi Sankyo Colony stimulating Tenosynovial giant cell Oral 8/3/19 factor-1 receptor tumor (TGCT) (CSF1R) inhibitor Entrectinib Genentech TrKA, TrKB, TrKC, ROS1, NTRK-fusion+ solid Oral 8/18/19 and ALK inhibitor tumors Polatuzumab Genentech Cytotoxic agent Large B-cell lymphoma IV 8/19/19 vedotin Fedratinib Celgene Selective JAK2 Myelofibrosis Oral 9/3/19 Darolutamide Bayer Prostate cancer Oral
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    Published OnlineFirst February 14, 2013; DOI: 10.1158/1535-7163.MCT-12-0305 Molecular Cancer Cancer Therapeutics Insights Therapeutics Transient Exposure to Quizartinib Mediates Sustained Inhibition of FLT3 Signaling while Specifically Inducing Apoptosis in FLT3-Activated Leukemia Cells Ruwanthi N. Gunawardane, Ronald R. Nepomuceno, Allison M. Rooks, Jeremy P. Hunt, Jill M. Ricono, Barbara Belli, and Robert C. Armstrong Abstract Fms-like tyrosine kinase 3 (FLT3) is implicated in the pathogenesis of acute myeloid leukemia (AML). FLT3-activating internal tandem duplication (ITD) mutations are found in approximately 30% of patients with AML and are associated with poor outcome in this patient population. Quizartinib (AC220) has previously been shown to be a potent and selective FLT3 inhibitor. In the current study, we expand on previous observations by showing that quizartinib potently inhibits the phosphorylation of FLT3 and downstream signaling molecules independent of FLT3 genotype, yet induces loss of viability only in cells expressing constitutively activated FLT3. We further show that transient exposure to quizartinib, whether in vitro or in vivo, leads to prolonged inhibition of FLT3 signaling, induction of apoptosis, and drastic reductions in tumor volume and pharmacodynamic endpoints. In vitro experiments suggest that these prolonged effects are mediated by slow binding kinetics that provide for durable inhibition of the kinase following drug removal/clearance. Together these data suggest quizartinib, with its unique combination of selectivity and potent/sustained inhibition of FLT3, may provide a safe and effective treatment against FLT3-driven leukemia. Mol Cancer Ther; 12(4); 1–10. Ó2013 AACR. Introduction downstream signaling cascades including the Ras/ Fms-like tyrosine kinase 3 (FLT3) is a member of the MAPK, PI3K/Akt, and STAT5 pathways (1, 9–13).
  • ARCTURUS THERAPEUTICS HOLDINGS INC. (Exact Name of Registrant As Specified in Its Charter)

    ARCTURUS THERAPEUTICS HOLDINGS INC. (Exact Name of Registrant As Specified in Its Charter)

    UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 20, 2020 ARCTURUS THERAPEUTICS HOLDINGS INC. (Exact name of registrant as specified in its charter) Delaware 001-38942 32-0595345 (State or other jurisdiction (Commission (I.R.S. Employer of incorporation) File Number) Identification No.) 10628 Science Center Drive, Suite 250 San Diego, California 92121 (Address of principal executive offices) Registrant’s telephone number, including area code: (858) 900-2660 (Former name or former address, if changed since last report) Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions: ☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) ☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) ☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) ☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) Securities registered pursuant to Section 12(b) of the Act: Trading Name of each exchange Title of each class Symbol(s) on which registered Common stock, par value $0.001 per share ARCT The NASDAQ Stock Market LLC Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
  • Letters to the Editor

    Letters to the Editor

    LETTERS TO THE EDITOR FLT3 inhibitor, sorafenib, induced no myelosuppression.5,6 Inhibition of c-Kit by tyrosine kinase inhibitors To better understand the relationship between inhibition of c-Kit, FLT3, and marrow suppression, we studied a series of different TKIs using bone marrow progenitor cell assays Several small molecule tyrosine kinase inhibitors (TKIs) and immunoblots. inhibit c-Kit, an effect associated with myelosuppression Cell lines were cultured as previously described.2 TF-1 and hair depigmentation. We studied a panel of approved cells were obtained from the American Type Culture and investigational TKIs for inhibitory activity against FLT3 Collection (ATCC; Manassas, VA, USA) and grown in and c-Kit, and on hematopoietic progenitor cells. Potent c- RPMI supplemented with GM-CSF (Invitrogen, Grand Kit inhibitors such as dasatinib, pazopanib, and quizartinib Island, NY, USA). Quizartinib was obtained from Ambit demonstrated the greatest disruption of hematopoietic pro- Biosciences (San Diego, CA, USA). Crenolanib was genitor cells, while sorafenib, which has negligible activity obtained from Arog Pharmaceuticals (Dallas, TX, USA). against c-Kit, demonstrated only minimal disruption. Our Dasatinib, pazopanib, and imatinib were obtained from LC data highlight the importance of determining a therapeutic Laboratories (Woburn, MA, USA). Electrophoresis, index between the targeted receptor and c-Kit for TKIs immunoblotting, and hematopoietic progenitor cell assays used to treat malignancies in order to maintain normal were performed as described.2 Cytokines used included hematopoiesis and improve outcomes. SCF, G-CSF, GM-CSF, IL-3, IL-6, and erythropoietin. Myelosuppression is a common adverse event in new Unused portions of bone marrow from normal donors drug development in oncology.