On February 28, 2019 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, today reported financial results for the fourth quarter and full year 2018 and provided a business update and an overview of recent accomplishments for selinexor, its first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound (Press release, Karyopharm, FEB 28, 2019, View Source [SID1234533807]).

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"Earlier this week, the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 8 to 5, recommending that the FDA wait for the results from the ongoing Phase 3 BOSTON study before making a final approval decision regarding selinexor for the treatment of patients with triple class refractory multiple myeloma who have received at least three prior therapies," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "While we are disappointed with the ODAC’s recommendation, we are encouraged by the support communicated by a number of ODAC members. We intend to work closely with the FDA to evaluate the best path forward as they complete their review of our New Drug Application (NDA). We remain committed to delivering on our vision of bringing selinexor into the hands of the physicians and patients who are battling highly refractory multiple myeloma."

Fourth Quarter 2018 and Recent Events

Selinexor in Multiple Myeloma

FDA Advisory Committee Recommends that the FDA Should Wait for Results from the Ongoing Phase 3 BOSTON Study Before Making an Approval Decision. On February 26, 2019, the Oncologic Drugs Advisory Committee (ODAC) of the FDA met to review data supporting Karyopharm’s NDA requesting accelerated approval for selinexor. The proposed indication discussed was for selinexor in combination with dexamethasone for the treatment of patients with relapsed refractory multiple myeloma who have received at least three prior therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody. The FDA specifically asked the ODAC to vote on whether the committee believed the approval of selinexor should be delayed until the results from the ongoing, randomized Phase 3 BOSTON study, are available. In a vote of 8 Yes and 5 No, the ODAC recommended that the approval decision for selinexor should be delayed until the results of the BOSTON study are available. Karyopharm’s NDA is under Priority Review by the FDA with an action date of April 6, 2019, under the PDUFA.
The ODAC is an independent panel of experts that evaluates data concerning the efficacy and safety of marketed and investigational products for use in the treatment of cancer and makes appropriate recommendations to the FDA. Although the FDA will consider the recommendation of the panel, the final decision regarding the approval of the product is made by the FDA solely, and the recommendations by the panel are non-binding.

FDA Accepts Selinexor New Drug Application and Grants Priority Review. On October 5, 2018, the FDA accepted for filing with Priority Review Karyopharm’s NDA seeking accelerated approval for selinexor, its first-in-class, oral SINE compound, as a new treatment for patients with triple class refractory multiple myeloma. The FDA also assigned a PDUFA action date of April 6, 2019.

Submitted Marketing Authorization Application (MAA) to the European Medicines Agency (EMA). A MAA was submitted to the EMA on January 8, 2019 for selinexor requesting conditional approval for the treatment of patients with relapsed or refractory multiple myeloma who have received at least three prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody. Karyopharm also announced that the selinexor MAA has been granted accelerated assessment by the EMA’s Committee for Medicinal Products for Human Use.

Updated Phase 2b STORM Data Presented at American Society of Hematology (ASH) (Free ASH Whitepaper) 2018 Annual Meeting (ASH 2018). Additional results from Part 2 of the Phase 2b STORM study were highlighted in an oral presentation at ASH (Free ASH Whitepaper) 2018. For the STORM study’s primary objective, the overall response rate (ORR) was 26.2%, which included two stringent complete responses (sCRs), six very good partial responses (VGPRs) and 24 partial responses (PRs) in patients with triple class refractory myeloma who have been previously exposed to all five of the most commonly prescribed anti-myeloma therapies currently available. The two sCRs were negative for minimal residual disease, one at the level of 1×10-6 and one at 1×10-4; this is particularly significant in this highly refractory population. The Disease Control Rate for patients who had achieved stable disease or better was 78.7%. All responses were confirmed by an Independent Review Committee. Median progression-free survival (PFS) was 3.7 months and the median duration of response (DOR) was 4.4 months. Median overall survival (OS) across the study was 8.6 months. Median OS in the approximately 40% of patients with at least a minimal response (MR) on selinexor and dexamethasone was 15.6 months compared to a median OS of 1.7 months in patients whose disease progressed or was not evaluable (p<0.0001). The short median OS of patients with no response to selinexor is consistent with the lack of available effective therapies for the very heavily pretreated population who entered the study. The most common adverse events (AEs) included thrombocytopenia, nausea/vomiting, fatigue and decreased appetite. Each patient on STORM experienced at least one AE. AEs were generally predictable and manageable with dose adjustments and/or supportive care, and treatment-emergent AEs leading to treatment discontinuation occurred in 26.8% of patients and these were considered by the Investigator to be treatment-related in 17.9% of patients. Major organ toxicities were not prominent in this study and safety results were consistent with those previously reported from Part 1 of the STORM study (Vogl et al., J Clin Oncol, 2018) and from other selinexor studies.

Updated Phase 1b/2 STOMP Data Presented at ASH (Free ASH Whitepaper) 2018. Two abstracts featuring clinical data from two treatment arms of the ongoing Phase 1b/2 STOMP study in patients with relapsed or refractory multiple myeloma were selected for oral and poster presentations at ASH (Free ASH Whitepaper) 2018. The oral presentation highlighted updated data from the arm evaluating selinexor in combination with Darzalex (daratumumab) and low-dose dexamethasone (SDd). In this arm, the combination demonstrated an ORR of 79% in patients with heavily pretreated, Darzalex-naïve multiple myeloma and an ORR of 73% in the overall study population. The poster presentation described updated data from the arm evaluating selinexor in combination with Pomalyst (pomalidomide) and low-dose dexamethasone (SPd). In this arm, the combination demonstrated an ORR of 54% in patients with Pomalyst-naïve and Revlimid-relapsed or -refractory multiple myeloma, with PFS of 12.2 months. The combination demonstrated an ORR of 50% in the overall study population. Among the patients evaluated for safety as of the data cutoff date, the most common treatment-related AEs were cytopenias, along with gastrointestinal and constitutional symptoms; most manageable with dose modifications and/or standard supportive care.

Pivotal Phase 3 BOSTON Study in Progress. Karyopharm’s pivotal, randomized Phase 3 BOSTON study is progressing and in January 2019, the Company announced the completion of enrollment in the study. Top-line data is expected at the earliest by the end of 2019 or into 2020 contingent upon the occurrence of PFS events, the primary endpoint in the study. The BOSTON study is evaluating 100mg of selinexor dosed once weekly in combination with the proteasome inhibitor Velcade (once weekly) and low dose dexamethasone (SVd), compared to standard twice weekly Velcade and low dose dexamethasone (Vd) in patients with multiple myeloma who have had one to three prior lines of therapy. Data from the BOSTON study, if positive, would be used to support regulatory submissions to the FDA and EMA requesting the use of selinexor in second line multiple myeloma, and confirming the Company’s requests for accelerated and conditional approvals, respectively, using data from the Phase 2b STORM study.
Selinexor in Diffuse Large B-Cell Lymphoma (DLBCL)

Received Fast Track Designation from FDA for the Treatment of Patients with Relapsed or Refractory DLBCL. In addition to Orphan Drug Designation, selinexor was recently granted Fast Track designation by the FDA for the treatment of patients with diffuse large B-cell lymphoma (DLBCL) who have received at least two prior therapies and are not eligible for high dose chemotherapy with stem cell rescue or CAR-T therapy.

Top-Line Phase 2b SADAL Data in DLBCL Presented at ASH (Free ASH Whitepaper) 2018. Top-line results from the fully enrolled Phase 2b SADAL study was presented at ASH (Free ASH Whitepaper) 2018. The SADAL study is designed to evaluate single agent oral selinexor 60mg for patients with relapsed or refractory DLBCL who are not eligible for stem cell transplantation. Based on the modified intention-to-treat analysis from the first 115 of 127 patients, as adjudicated by an independent central radiological committee, selinexor achieved an ORR of 29.6%. The median DOR across responding patients was 9.2 months. Patients with a complete response (CR) had a median DOR of 23.0 months and patients with a PR had a median DOR of 7.8 months. The median OS was 9.1 months for all patients in the study. As of the data cutoff date, median survival for the patients with a CR or PR was 29.7 months. The median survival for patients with best response of progressive disease or who were not evaluable for response was 3.2 months. Among the patients evaluated for safety as of the data cutoff date, the most common treatment-related AEs were gastrointestinal and constitutional symptoms, along with cytopenias; most AEs were manageable with dose modifications and/or supportive care. Based on the results from the Phase 2b SADAL study, Karyopharm plans to submit an NDA to the FDA with a request for accelerated approval for oral selinexor in this relapsed or refractory DLBCL patient population and the Company is working closely with the FDA to determine the appropriate timeline. Karyopharm is also planning to submit a MAA to the EMA with a request for conditional approval in the same indication.
Selinexor in Solid Tumors

Ongoing Phase 3 Portion of the Phase 2/3 SEAL Study in Liposarcoma. Karyopharm previously reported results from the successful Phase 2 portion of the blinded, randomized Phase 2/3 SEAL study evaluating single-agent selinexor versus placebo in patients with previously treated, advanced unresectable dedifferentiated liposarcoma. Enrollment and dosing are currently ongoing in the Phase 3 portion of the SEAL study and, assuming a positive outcome on the primary end point of PFS, the Company intends to use the data from the SEAL study to support a NDA and a MAA submission requesting approval for oral selinexor for patients with advanced unresectable dedifferentiated liposarcoma. Top-line data from the Phase 3 portion of the SEAL study are anticipated in 2020.

Ongoing Investigator Sponsored Phase 2/3 Trial as Maintenance Therapy in Endometrial Cancer. A randomized Phase 2/3 study of selinexor versus placebo as maintenance therapy in patients with one or two prior platinum-based treatments for advanced endometrial cancer, led by Dr. Ignace Vergote, Head of the Department of Obstetrics and Gynaecology and Gynaecologic Oncology at the Catholic University of Leuven, Belgium, is currently ongoing. Top-line data from this study are anticipated in 2020.
Corporate Updates

Michael P. Mason Appointed Chief Financial Officer. Karyopharm announced the appointment of Michael P. Mason as Chief Financial Officer. Mr. Mason formerly served as Vice President of Finance and Treasurer at Alnylam Pharmaceuticals, Inc., a public biopharmaceutical company. He brings over 18 years of diversified financial experience to Karyopharm and has deep expertise in global financial operations and controls, financing transactions, business planning and supporting pharmaceutical product launches.
Full Year and Fourth Quarter 2018 Financial Results

Cash, cash equivalents and investments as of December 31, 2018, including restricted cash, totaled $330.9 million, compared to $176.4 million as of December 31, 2017.

On October 26, 2018, Karyopharm completed a private offering of $172.5 million aggregate principal amount of 3.00% convertible senior notes due in 2025, including the full exercise of the initial purchasers’ option to purchase additional notes. After deducting the initial purchasers’ discounts and commissions and other offering expenses the net proceeds were $166.9 million.

License and other revenue for the year ended December 31, 2018 was $30.3 million, compared to $1.6 million for the year ended December 31, 2017, primarily related to the Company’s license agreements with Biogen and ONO.

For the year ended December 31, 2018, research and development expense was $161.4 million compared to $107.3 million for the year ended December 31, 2017. For the year ended December 31, 2018, general and administrative expense was $48.8 million compared to $24.9 million for the year ended December 31, 2017.

Karyopharm reported a net loss of $178.4 million, or $3.14 per share, for the year ended December 31, 2018, compared to a net loss of $129.0 million, or $2.81 per share, for the year ended December 31, 2017. Net loss includes stock-based compensation expense of $17.3 million and $20.4 million for the years ended December 31, 2018 and December 31, 2017, respectively.

For the quarter ended December 31, 2018, research and development expense was $38.9 million, compared to $34.8 million for the quarter ended December 31, 2017. For the quarter ended December 31, 2018, general and administrative expense $18.8 million, compared to $6.2 million for the quarter ended December 31, 2017.

Karyopharm reported a net loss of $58.2 million, or $0.96 per share for the quarter ended December 31, 2018, compared to a net loss of $39.0 million, or $0.80 per share for the quarter ended December 31, 2017. Net loss includes stock-based compensation expense of $3.9 million and $4.5 million for the quarters ended December 31, 2018 and December 31, 2017, respectively.

Financial Outlook

Based on its current operating plans, Karyopharm expects that its existing cash, cash equivalents and investments will be sufficient to fund its operations into the second half of 2020, which currently assumes the commercial launch of selinexor in the U.S. in the second quarter of 2019. If the FDA decides to delay its approval decision for selinexor until the BOSTON data is available, Karyopharm will re-evaluate its spending expectations for 2019. Additional key activities expected in 2019 include supporting the ongoing multiple myeloma regulatory filings for selinexor in the U.S. and Europe, progressing the pivotal Phase 3 BOSTON study in multiple myeloma and potentially submitting an NDA and MAA, in the U.S. and Europe, respectively, in DLBCL.

Further Information About Potential Accelerated Approval for Selinexor in Multiple Myeloma

The FDA instituted its Accelerated Approval Program to allow for expedited approval of drugs that treat serious conditions and that fill an unmet medical need based on a surrogate endpoint or an intermediate clinical endpoint thought to predict clinical benefit, like overall response rate. Accelerated approval is available only for drugs that provide a meaningful therapeutic benefit over existing treatments at the time of consideration of the application for accelerated approval, which the FDA has reiterated in its feedback to the Company. Particularly in disease areas with multiple available and potential new therapies, such as multiple myeloma, accelerated approval carries a high regulatory threshold. Consistent with its general guidance, the FDA has noted to the Company its preference for randomized studies geared toward full approval, which the Company has undertaken with the ongoing pivotal, Phase 3 BOSTON study, and has reminded the Company that accelerated approval requires patients to have exhausted all available approved therapies.

Conference Call Information

Karyopharm will host a conference call today, Thursday, February 28, 2019, at 8:30 a.m. Eastern Time, to discuss the fourth quarter and full year 2018 financial results, recent accomplishments, clinical developments and business plans. To access the conference call, please dial (855) 437-4406 (local) or (484) 756-4292 (international) at least 10 minutes prior to the start time and refer to conference ID 4246798. A live audio webcast of the call will be available under "Events & Presentations" in the Investor section of the Company’s website, View Source An archived webcast will be available on the Company’s website approximately two hours after the event.

On February 28, 2019 Sangamo Therapeutics, Inc. (NASDAQ: SGMO), a genomic medicine company, reported fourth quarter and full year 2018 financial results and recent business highlights (Press release, Sangamo Therapeutics, FEB 28, 2019, View Source [SID1234533806]).

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Recent Highlights

ST-920 IND acceptance: The U.S. Food and Drug Administration (FDA) accepted the Investigational New Drug application (IND) for ST-920, a gene therapy candidate being evaluated for the treatment of adults with Fabry disease. Sangamo expects to initiate the Phase 1/2 clinical trial evaluating ST-920 later this year.

WORLDSymposium presentations: At the WORLDSymposium earlier in February, Sangamo presented interim results from the Phase 1/2 CHAMPIONS and EMPOWERS studies evaluating SB-913 and SB-318, zinc finger nuclease (ZFN) in vivo genome editing product candidates for the treatment of Mucopolysaccharidosis Type II (MPS II) and MPS I, respectively. Sangamo believes data from these two studies provide complementary evidence supportive of a favorable safety profile and of the activity of the ZFN in vivo genome editing approach used in both SB-913 and SB-318.

EVP of R&D appointment: Sangamo appointed Adrian Woolfson, BM BCh, PhD, as Executive Vice President of Research and Development.

Completion of acquisition of TxCell: In the fourth quarter of 2018, Sangamo completed the acquisition of TxCell, SA. The acquisition positions Sangamo as a leader in the development of CAR-Tregs, which the Company plans to evaluate for solid organ transplant rejection and for autoimmune diseases.

"The enrollment of patients last year into our five active clinical trials has laid the foundation for a steady flow of data readouts in 2019," said Sandy Macrae, CEO of Sangamo. "In the remainder of the year, we anticipate providing important data that will help us understand the potential clinical benefit of our MPS I and MPS II programs, as well as clinical results and analyses from three clinical hematology assets for hemophilia A, hemophilia B and beta thalassemia. We also expect four additional programs to progress into clinical development, including our wholly owned gene therapy for Fabry disease and CAR-Treg therapy for the prevention of solid organ transplant rejection, as well as partnered programs in sickle cell disease and oncology being developed in collaboration with Sanofi and Kite, respectively. I’m excited for what lies ahead as we continue to push forward the development of our genomic medicines."

Anticipated Milestones in 2019

In Vivo Genome Editing

SB-913: Nine patients are enrolled in the CHAMPIONS Study evaluating SB-913 for MPS II, including three patients who recently entered the study in the expanded high-dose cohort. In 2019, Sangamo expects to report longer-term safety and biochemical measurements, as well as analyses of liver biopsies and enzyme replacement therapy withdrawal experience.

SB-318: Three patients are enrolled in the EMPOWERS Study evaluating SB-318 for MPS I. In 2019, Sangamo expects to report longer-term safety and biochemical measurements, as well as analyses of liver biopsies and enzyme replacement therapy withdrawal experience.

SB-FIX: One patient is currently enrolled in the FIXtendz Study evaluating SB-FIX for hemophilia B. Sangamo expects to enroll a second subject in the study and later in 2019 to report data including safety and factor expression levels.

Second-generation reagents for in vivo genome editing platform: Sangamo has developed second-generation albumin locus ZFN constructs for potential use in the ongoing in vivo genome editing development programs. The Company plans to initiate a clinical trial this year using these second-generation ZFNs that should enable a Phase 3 decision for the MPS II program in 2020.

Gene Therapy

SB-525: Eight patients are enrolled in the Alta Study evaluating SB-525 gene therapy for hemophilia A, being developed in collaboration with Pfizer. In 2019, Sangamo expects to report data including safety and factor expression levels, as well as information regarding factor replacement use and bleeding events.

ST-920: In 2019, Sangamo anticipates activating sites for the Phase 1/2 clinical trial evaluating ST-920 gene therapy for the treatment of Fabry disease.

Ex Vivo Cell Therapy

ST-400 and BIVV003: ST-400 and BIVV003 are gene-edited cell therapies being developed in collaboration with Sanofi for the treatment of beta thalassemia and sickle cell disease. Sangamo has enrolled two patients in the Thales Study evaluating ST-400 for the treatment of beta thalassemia and in 2019 expects to report initial safety and efficacy data including levels of fetal hemoglobin and total hemoglobin. BIVV003 is being evaluated for the treatment of sickle cell disease in the Phase 1/2 PRECIZN-1 trial run by Sanofi.

TX200: In 2019, Sangamo anticipates filing a clinical trial application in Europe for TX200, an autologous CAR-Treg cell therapy for the prevention of solid organ transplant rejection. The Company expects to activate clinical sites by year-end.

KITE-037: Kite, a Gilead Company, has announced the intention to file an IND for KITE-037, an allogeneic anti-CD19 CAR-T cell therapy, in the latter half of 2019.

Fourth Quarter 2018 Financial Results

For the fourth quarter ended December 31, 2018, Sangamo reported a consolidated net loss of $18.7 million, or $0.18 per share, compared to a net loss of $13.1 million, or $0.15 per share, for the same period in 2017. As of December 31, 2018, the Company had cash, cash equivalents, marketable securities and interest receivable of $400.5 million.

Revenues for the fourth quarter ended December 31, 2018 were $26.8 million, compared to $13.1 million for the same period in 2017. The increase came primarily from approximately $11.5 million in revenues related to the collaboration agreements with Pfizer for hemophilia A, and $9.0 million in revenues related to the collaboration with Kite, a Gilead Company, which included reimbursement of $2.7 million in research services. Fourth quarter 2018 revenues were primarily generated from Sangamo’s collaboration agreements with Pfizer, Kite, Sanofi, and Dow Agrosciences.

Total operating expenses for the fourth quarter ended December 31, 2018 were $47.6 million, compared to $26.8 million for the same period in 2017. Research and development expenses were $33.3 million for the fourth quarter of 2018, compared to $19.4 million for the same period in 2017. The increase was primarily due to manufacturing and clinical trial expenses related to the progress of the Company’s clinical development programs. General and administrative expenses were $14.4 million for the fourth quarter of 2018, compared to $7.5 million for the same period in 2017. This increase was primarily due to increased headcount in general support of growth for the Company’s pipeline and clinical programs.

Full Year 2018 Results

For the year ended December 31, 2018, the consolidated net loss was $68.3 million, or $0.70 per share, compared to a consolidated net loss of $54.6 million, or $0.70 per share, for the year ended December 31, 2017. Revenues were $84.5 million for the year ended December 31, 2018, compared to $36.6 million for the same period in 2017. The increase in revenues was primarily related to our collaboration and license agreements with Kite and Pfizer. Total operating expenses were $161.6 million for the year ended December 31, 2018, compared to $92.9 million for the same period in 2017. The increase in operating expenses was primarily related to overall Company growth and manufacturing and R&D expenses related to the advancement of Sangamo’s therapeutic pipeline.

Financial Guidance for 2019

Operating Expense: Sangamo expects operating expense of $210 to 220 million for the year ending December 31, 2019.

Cash and Investments: Sangamo projects that current cash, cash equivalents, marketable securities and interest receivable position should last at least two years.

Conference Call

Sangamo will host a conference call today, February 28, 2019, at 5:00 p.m. Eastern Time, which will be open to the public. The call will also be webcast live and can be accessed via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations.

The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 6875578. For those unable to listen in at the designated time, a conference call replay will be available for one week following the conference call, from approximately 8:00 p.m. ET on February 28, 2019 to 11:59 p.m. ET on March 7, 2019. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 6875578.

On February 28, 2019 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage company developing highly differentiated therapeutics targeting the underlying mechanisms of cancer, reported that preclinical data for CG-806, its first-in-class, highly potent oral small molecule pan-FLT3/pan-BTK inhibitor, and APTO-253, its MYC inhibitor, will be presented in two separate posters at the 2019 AACR (Free AACR Whitepaper) Annual Meeting in Atlanta, GA (Press release, Aptose Biosciences, FEB 28, 2019, View Source [SID1234533805]).

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CG-806 Poster Presentation Details:

CG-806, a pan-FLT3 / pan-BTK inhibitor, demonstrates superior potency against cells from IDH-1 mutant and other non-favorable risk groups of AML patients
Date & Time: Monday, April 1, 2019, 8:00 a.m. – 12:00 p.m.
Session Category: Experimental and Molecular Therapeutics
Session Title: Tyrosine Kinase and Phosphatase Inhibitors 1
Abstract Number: 1323
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 15

APTO-253 Poster Presentation Details:

Resistance to APTO-253 caused by internal deletion and alternate promoter usage of the MYC gene in malignant B cells
Date & Time: Monday, April 1, 2019, 1:00 p.m. – 5:00 p.m.
Session Category: Experimental and Molecular Therapeutics
Session Title: Drug Resistance 3
Abstract Number: 2096
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 15

All abstracts will be available on the AACR (Free AACR Whitepaper) website, www.aacr.org, and published in the 2018 Proceedings of the AACR (Free AACR Whitepaper).

About CG-806
CG-806 is an oral, first-in-class pan-FLT3/pan-BTK multi-cluster kinase inhibitor. This small molecule, in-licensed from CrystalGenomics Inc. in Seoul S. Korea, demonstrates potent inhibition of wild type and all mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), cures animals of acute myeloid leukemia (AML) tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML. Likewise, CG-806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser (C481S) mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting CG-806 may be developed for various B cell malignancy patients (including CLL, SLL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent BTK inhibitors. Because CG-806 targets key kinases/pathways operative in malignancies derived from the bone marrow, it is in development for B cell cancers and AML.

About APTO-253
APTO-253 is a clinical-stage, small molecule, targeted therapeutic agent that inhibits expression of the MYC oncogene, leading to cell cycle arrest and programmed cell death (apoptosis) in human-derived solid tumor and hematologic cancer cells. The MYC oncogene is overexpressed in hematologic cancers, including acute myeloid leukemia (AML). Aptose researchers have reported the ability of APTO-253 to induce cell death, or apoptosis, in multiple blood cancer cell lines including AML, as well as in vitro synergy with various classes of conventional approved and investigational therapies for AML or myelodysplastic syndromes (MDS). New findings reveal that APTO-253 might also serve certain solid tumor patients with BRCA1/2 mutations, but without causing toxicity to the normal bone marrow functions.

On February 28, 2019 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported that it will participate in the 39th Annual Cowen Health Care Conference on Tuesday, March 12, 2019 (Press release, AbbVie, FEB 28, 2019, https://news.abbvie.com/news/press-releases/abbvie-to-present-at-cowen-health-care-conference.htm [SID1234533803]). Richard A. Gonzalez, chairman and chief executive officer, will present at 7:00 a.m. Central time.

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A live audio webcast of the presentation will be accessible through AbbVie’s Investor Relations website at investors.abbvie.com. An archived edition of the session will be available later that day.

On February 28, 2019 gle Pharmaceuticals, Inc. ("Eagle" or the "Company") (Nasdaq: EGRX) reported its financial results for the three months and full year ended December 31, 2018 (Press release, Eagle Pharmaceuticals, FEB 28, 2019, View Source [SID1234533800]). Highlights of, and subsequent to, the fourth quarter of 2018 include:

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Business and Recent Highlights:

· Commenced enrollment in a study to evaluate the neuroprotective effects of RYANODEX (dantrolene sodium) in collaboration with the United States Army Medical Research Institute of Chemical Defense ("USAMRICD"), the nation’s leading science and technology laboratory in the area of medical chemical countermeasures research and development;

· Announced positive results of pre-clinical study conducted to evaluate effects of RYANODEX in Acute Radiation Syndrome ("ARS");

·On February 20, 2019, the FDA issued a decision in favor of Eagle regarding the scope of BENDEKA’s Orphan Drug Exclusivity ("ODE"), further protecting the longevity of the BENDEKA franchise; and

·Executed a $50.0 million accelerated share repurchase ("ASR") as part of our $150.0 million share repurchase program (the "Share Repurchase Program").

Financial Highlights:

Fourth Quarter 2018

· Total revenue for the fourth quarter of 2018 was $56.1 million, compared to $46.8 million in the fourth quarter of 2017;

· Q4 2018 bendamustine hydrochloride 500ml solution ("Big Bag" or "BELRAPZO") product sales were $6.8 million; in February of 2019, the Company achieved peak market share of 10%, according to IQVIA Holdings Inc.;

· Q4 2018 RYANODEX product sales were $5.1 million, up 10% compared to Q4 2017;

· Q4 2018 net income was $12.6 million, or $0.88 per basic and $0.86 per diluted share, compared to net income of $9.1 million, or $0.61 per basic and $0.58 per diluted share in Q4 2017;

· Q4 2018 adjusted non-GAAP net income was $17.7 million, or $1.23 per basic and $1.20 per diluted share, compared to adjusted non-GAAP net income of $15.6 million, or $1.05 per basic and $1.00 per diluted share in Q4 2017; and

·Q4 2018, Eagle executed a $50.0 million ASR of common stock as part of the Share Repurchase Program.

Full Year 2018

· Total revenue for the twelve months ended December 31, 2018 was $213.3 million, compared to $236.7 million in 2017 including $37.5 million in milestone payments for BENDEKA, reflecting revenue growth of 7% when excluding milestone payments;

·2018 net income was $31.9 million, or $2.16 per basic and $2.09 per diluted share, compared to net income of $51.9 million, or $3.44 per basic and $3.27 per diluted share in 2017;

· 2018 adjusted non-GAAP net income was $59.2 million, or $4.01 per basic and $3.87 per diluted share, compared to adjusted non-GAAP net income of $69.0 million, or $4.57 per basic and $4.34 per diluted share in 2017;

· From August 2016 through December 31, 2018, Eagle has repurchased $154.0 million of its common stock; and

· Cash and cash equivalents were $78.8 million, accounts receivable was $66.5 million, and debt was $45.0 million as of December 31, 2018.

"We had another outstanding quarter, nearly doubling our product sales in Q4 2018 compared to Q4 2017 and generating 20% growth in total quarterly revenue year over year. We were able to deliver substantial cash flow throughout the year, repurchase $78 million of our own shares, and maintain a very strong balance sheet with which to execute our development and commercial activities," stated Scott Tarriff, Chief Executive Officer of Eagle Pharmaceuticals.

"There are multiple exciting opportunities we plan to advance in 2019. The study initiated with the U.S. Military to evaluate RYANODEX in the treatment of nerve agent exposure is progressing nicely. Three of the six animal cohorts have now been challenged. The results of our pre-clinical study to evaluate the effect of RYANODEX in treating ARS are encouraging, and we are continuing our dialogue with the FDA regarding a path forward for EHS. As the year unfolds, we look forward to gaining greater clarity regarding our pipeline, exploring new opportunities with existing products, and delivering a very efficient business model that provides the cash necessary to execute our development, commercial activities, and potential licensing opportunities," concluded Tarriff.

Fourth Quarter 2018 Financial Results

Total revenue for the three months ended December 31, 2018 was $56.1 million, as compared to $46.8 million for the three months ended December 31, 2017. Royalty revenue was $35.7 million, compared to $36.4 million in the fourth quarter of 2017. BENDEKA royalties were $31.9 million, compared to $34.7 million in the fourth quarter of 2017. A summary of total revenue is outlined below:

Gross Margin was 67% during the fourth quarter of 2018, as compared to 71% in the fourth quarter of 2017. The year over year compression in gross margin resulted from the introduction of Big Bag revenue was partly offset by an expansion in RYANODEX gross margin.

R&D expenses were $5.9 million for the quarter, compared to $9.4 million in the prior year quarter. The fourth quarter year over year decrease reflects a substantial reduction in fulvestrant expenses, partially offset by the cost of analytical work to support our vasopressin ANDA. Excluding stock-based compensation and other non-cash and non-recurring items, R&D expense during the fourth quarter was $4.4 million.

SG&A expenses in the fourth quarter of 2018 increased to $15.5 million in the fourth quarter of 2018 compared to $13.4 million in the fourth quarter of 2017. External legal expenses account for the year over year increase. Excluding stock-based compensation and other non-cash and non-recurring items, fourth quarter 2018 SG&A expense was $11.3 million.

Net income for the fourth quarter of 2018 was $12.6 million, or $0.88 per basic and $0.86 per diluted share, compared to net income of $9.1 million, or $0.61 per basic and $0.58 per diluted share in the three months ended December 31, 2017, due to the factors discussed above.

Adjusted non-GAAP net income for the fourth quarter of 2018 was $17.7 million, or $1.23 per basic and $1.20 per diluted share, compared to adjusted non-GAAP net income of $15.6 million or $1.05 per basic and $1.00 per diluted share in the fourth quarter of 2017. For a full reconciliation of adjusted non-GAAP net income to the most comparable GAAP financial measures, please see the tables at the end of this press release.

Full Year 2018 Financial Results

The increase in product sales in 2018 was driven primarily by the launch of Big Bag, as well as continued growth in RYANODEX revenue. Royalty revenue totaled $142.9 million in 2018 compared to $153.9 million in 2017. In 2018, Eagle did not earn any license and other income. In 2017, Eagle earned certain contractual milestones in connection with the Company’s BENDEKA licensing agreement with Teva, as well as an upfront payment associated with the SymBio collaboration covering Japanese rights for bendamustine hydrochloride ready-to-dilute and rapid infusion injection products.

Gross margin was 71% in 2018, as compared to 76% in 2017. The year over year compression in gross margin resulted from the introduction of Big Bag revenue was partly offset by an expansion in RYANODEX gross margin.

R&D expense increased to $44.4 million in 2018, compared to $32.6 million in 2017, reflecting the cost of the fulvestrant trial as well as the vasopressin analytical work. Excluding stock-based compensation and other non-cash and non-recurring items, R&D expense in 2018 was $37.8 million.

SG&A expenses decreased by $10.9 million to $60.5 million in 2018, compared to $71.4 million in 2017. In 2017, SG&A included increased marketing expense related to exertional heat stroke ("EHS") and the contract sales force agreement with Spectrum. The elimination of those expenses in 2018 was partly offset by an increase in external legal expenses. Excluding stock-based compensation and other non-cash and non-recurring items, SG&A expense in 2018 was $43.1 million.

Net income for the year ended December 31, 2018 was $31.9 million or $2.16 per basic and $2.09 per diluted share as compared to net income of $51.9 million or $3.44 per basic and $3.27 per diluted share for the year ended December 31, 2017, as a result of the factors discussed above.

Adjusted non-GAAP net income for 2018 was $59.2 million, or $4.01 per basic and $3.87 per diluted share, compared to adjusted non-GAAP net income of $69.0 million, or $4.57 per basic and $4.34 per diluted share in 2017.

Liquidity

As of December 31, 2018, the Company had $78.8 million in cash and cash equivalents and $66.5 million in net accounts receivable, $41.8 million of which was due from Teva Pharmaceutical Industries Ltd. The Company had $45.0 million in outstanding debt.

In the fourth quarter of 2018, we purchased $50.0 million of Eagle’s common stock as part of our $150.0 million Share Repurchase Program. From August 2016 through December 31, 2018, we have repurchased $154.0 million of our common stock, including the $50.0 million ASR. As disclosed on October 30, 2018, the Company’s Board of Directors retired the prior share repurchase programs and approved the new $150.0 million Share Repurchase Program (which includes the ASR).

Conference Call

As previously announced, Eagle management will host its fourth quarter and full year 2018 conference call as follows:

Date

Thursday, February 28, 2019

Time

8:30 A.M. EST

Toll free (U.S.)

877-876-9177

International

785-424-1672

Webcast (live and replay)

www.eagleus.com, under the "Investor + News" section

A replay of the conference call will be available for one week after the call’s completion by dialing 800-283-4799 (US) or 402-220-0860 (International) and entering conference call ID EGRXQ418. The webcast will be archived for 30 days at the aforementioned URL.