On March 15, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported financial results for the fourth quarter and full year 2017 and provided an overview of recent accomplishments and clinical development plans for selinexor, its lead, novel, oral SINE compound, and eltanexor, its second-generation oral SINE compound Karyopharm Therapeutics Inc. (Nasdaq:KPTI), (Press release, Karyopharm, MAR 15, 2018, View Source [SID1234524794]).

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"2017 was a year of significant achievement for Karyopharm where we reported positive clinical data from our lead selinexor programs, including the Phase 1b/2 STOMP study in multiple myeloma (MM), the Phase 2b SADAL study in diffuse large B-cell lymphoma (DLBCL), and the Phase 2/3 SEAL study in liposarcoma, and the subsequent advancement of each study," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "We are looking forward to an event-driven 2018 beginning at the end of April with top-line results from the Phase 2b STORM study, followed by top-line data from the Phase 2b SADAL study by the year end. Assuming positive outcomes, we plan to use the data from both of these studies to support requests for accelerated approval from the U.S. Food and Drug Administration (FDA) and conditional approval from the European Medicines Agency (EMA) in these indications. On the corporate front, we continue to build out our commercial team in anticipation of a potential selinexor launch in the U.S. in 2019."

Fourth Quarter 2017 and Recent Events

New Strategic Relationships

Biogen’s Acquisition of KPT-350 for the Treatment of Neurological and Neurodegenerative Diseases. In January 2018, Karyopharm announced its entry into an agreement with Biogen to acquire Karyopharm’s investigational oral SINE compound KPT-350 targeting certain neurological and neurodegenerative conditions, including amyotrophic lateral sclerosis (ALS). The transaction carries a total deal value of up to $217 million, plus royalties.

Exclusive License Agreement with Ono Pharmaceutical Co., Ltd. (Ono) to Develop and Commercialize Selinexor and Eltanexor in Japan and Other Countries in Asia. In October 2017, Karyopharm announced its entry into an exclusive license agreement with Ono for the development and commercialization of selinexor and eltanexor. The agreement includes the development of selinexor and eltanexor for the diagnosis, treatment and/or prevention of all human oncology indications in Japan, South Korea, Taiwan, Hong Kong, and the ASEAN countries (the Territory). The transaction carries a total deal value of up to $193.0 million based on the exchange rate on the effective date of the license agreement plus royalties. Karyopharm retains all rights to selinexor and eltanexor outside the Territory.
Selinexor in Multiple Myeloma

Ongoing Phase 2b STORM Study Expansion in Patients with Penta-refractory MM. Karyopharm expects to report top-line data from the expanded STORM study cohort at the end of April 2018, and, assuming a positive outcome, intends to use the data from this study to support a request for accelerated approval from the FDA and conditional approval from the EMA for oral selinexor for penta-refractory MM. The Phase 2b STORM study was previously expanded to include 122 additional patients with penta-refractory MM.

Pivotal Phase 3 BOSTON Study Underway. Karyopharm’s pivotal, randomized Phase 3 BOSTON (Bortezomib, Selinexor and dexamethasone) study is now underway and enrolling patients in 14 countries globally. BOSTON is designed to evaluate 100mg of selinexor dosed once weekly in combination with the proteasome inhibitor Velcade (once weekly) and dexamethasone (SVd), compared to standard twice weekly Velcade and low-dose dexamethasone (Vd) in patients with MM who have had one to three prior lines of therapy. The primary endpoints of the study are progression free survival and overall response rate. Both the trial design and endpoints have been agreed to by the FDA and the EMA as acceptable to support an application for approval. The Company expects to enroll approximately 360 patients at over 100 clinical sites internationally and is expecting completion of enrollment in 2018, with top-line data anticipated in 2019.

Positive Phase 1b/2 STOMP Data Presented at ASH (Free ASH Whitepaper) 2017. Data presentations featuring clinical results from four treatment arms of the ongoing Phase 1b/2 STOMP study evaluating selinexor in combination with standard therapies for the treatment of patients with MM were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2017 Annual Meeting (ASH 2017). Collectively, the STOMP study data presented at ASH (Free ASH Whitepaper) 2017 continue to provide evidence of tolerability and robust anti-myeloma activity when selinexor is combined with the currently available standard myeloma therapies, including proteasome inhibitors including Velcade, immunomodulatory drugs and anti-CD38 monoclonal antibodies. Additional treatment arms with selinexor in patients with newly diagnosed disease in combination with lenalidomide, and in combination with the proteasome inhibitor Kyprolis (carfilzomib) have been added.
Selinexor in Diffuse Large B-Cell Lymphoma

Ongoing Phase 2b SADAL Study in DLBCL. Karyopharm is also investigating oral selinexor as a single-agent for the treatment of patients with relapsed or refractory DLBCL. The SADAL study is expected to enroll up to a total of 130 patients in the single-arm cohort evaluating single-agent selinexor dosed 60mg twice weekly in patients with two or more lines of prior therapy. Karyopharm plans to report top-line results by the end of 2018, and assuming a positive outcome, the Company intends to use the data from the SADAL study to support a request for accelerated approval from the FDA and conditional approval from the EMA for oral selinexor in this relapsed/refractory DLBCL patient population.
Selinexor in Solid Tumors

Phase 3 Portion of the Phase 2/3 SEAL Study in Liposarcoma Underway. Karyopharm previously reported a successful outcome from the 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. The Phase 3 portion is underway and, assuming a positive outcome on the primary end point of progression free survival, the Company intends to use the data from the Phase 2/3 SEAL study to support a New Drug Application in the U.S. and a Marketing Authorization Application (MAA) in Europe for oral selinexor as a potential new treatment for patients with advanced unresectable dedifferentiated liposarcoma. Top-line data from the Phase 3 portion of the SEAL study are anticipated by the end of 2019.

Initiation of Investigator Sponsored Phase 2/3 Trial as Maintenance Therapy in Endometrial Cancer Underway. A randomized Phase 2/3 study of selinexor vs. placebo as maintenance therapy in patients with 1-2 prior platinum-based treatments for advanced endometrial cancer lead by Dr. Ignace Vergote, Head of the Department of Obstetrics and Gynaecology and Gynaecologic Oncology at the Catholic University of Leuven, Belgium, has been initiated.
Eltanexor

Positive Phase 1/2 Eltanexor Data Presented at ASH (Free ASH Whitepaper) 2017. Data from a Phase 1/2 study evaluating oral eltanexor in 34 patients with heavily pretreated MM was also presented at ASH (Free ASH Whitepaper) 2017. The data showed that eltanexor, both alone or in combination with low-dose dexamethasone, induced responses or disease control and was associated with prolonged survival. The study has been expanded to evaluate eltanexor in patients with advanced colorectal cancer (CRC), castration-resistant prostate cancer (crPC), and myelodysplastic syndrome (MDS). These are indications where selinexor and XPO1 inhibition has shown clear activity, but where the reduced side effects of eltanexor may permit more extended dosing.
Fourth Quarter and Year Ended December 31, 2017 Financial Results

Cash, cash equivalents and investments as of December 31, 2017, including restricted cash, totaled $176.4 million, compared to $175.5 million as of December 31, 2016.

For the year ended December 31, 2017, research and development expense was $107.3 million compared to $86.9 million for the year ended December 31, 2016. For the year ended December 31, 2017, general and administrative expense was $24.9 million compared to $23.9 million for the year ended December 31, 2016.

Karyopharm reported a net loss of $129.0 million, or $2.81 per share, for the year ended December 31, 2017, compared to a net loss of $109.6 million, or $2.92 per share, for the year ended December 31, 2016. Net loss includes stock-based compensation expense of $20.4 million and $22.3 million for the years ended December 31, 2017 and December 31, 2016, respectively.

For the quarter ended December 31, 2017, research and development expense was $34.8 million compared to $20.7 million for the quarter ended December 31, 2016. The increase in research and development expenses resulted primarily from increased expenses on our late stage clinical trials for selinexor and from payments of a portion of the upfront fees we received under our license agreement with Ono. For the quarter ended December 31, 2017, general and administrative expense was $6.2 million compared to $6.5 million for the quarter ended December 31, 2016. Karyopharm reported a net loss of $39.0 million, or $0.80 per share for the quarter ended December 31, 2017, compared to a net loss of $26.9 million, or $0.65 per share, for the quarter ended December 31, 2016. Net loss includes stock-based compensation expense of $4.5 million and $5.1 million for the quarters ended December 31, 2017 and December 31, 2016, respectively.

Financial Outlook

Based on current operating plans, Karyopharm expects that its existing cash, cash equivalents and investments will be sufficient to fund its operations through at least the first quarter of 2019. These plans include the continued clinical development of selinexor in the Company’s lead indications with a focus on filing an NDA with the FDA requesting accelerated approval in MM during 2018, assuming positive data from the STORM study, and preparing the commercial infrastructure for the potential launch of selinexor in the United States. Additional key milestones expected in 2018 include a potential MAA filing to the EMA requesting conditional approval for selinexor in MM, topline data from the SADAL study and completion of enrollment in the Phase 3 BOSTON study.

Conference Call Information

Karyopharm will host a conference call today, Thursday, March 15, 2018, at 8:30 a.m. Eastern Time, to discuss the fourth quarter and full year 2017 financial results, recent accomplishments, clinical developments and business plans. To access the conference call, please dial (855) 437-4406 or (484) 756-4292 (international) at least five minutes prior to the start time and refer to conference ID: 1181109. An audio recording of the call will be available under "Events & Presentations" in the "Investor" section of Karyopharm’s website, View Source, approximately two hours after the event..

"2017 was a year of significant achievement for Karyopharm where we reported positive clinical data from our lead selinexor programs, including the Phase 1b/2 STOMP study in multiple myeloma (MM), the Phase 2b SADAL study in diffuse large B-cell lymphoma (DLBCL), and the Phase 2/3 SEAL study in liposarcoma, and the subsequent advancement of each study," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "We are looking forward to an event-driven 2018 beginning at the end of April with top-line results from the Phase 2b STORM study, followed by top-line data from the Phase 2b SADAL study by the year end. Assuming positive outcomes, we plan to use the data from both of these studies to support requests for accelerated approval from the U.S. Food and Drug Administration (FDA) and conditional approval from the European Medicines Agency (EMA) in these indications. On the corporate front, we continue to build out our commercial team in anticipation of a potential selinexor launch in the U.S. in 2019."

Fourth Quarter 2017 and Recent Events

New Strategic Relationships

Biogen’s Acquisition of KPT-350 for the Treatment of Neurological and Neurodegenerative Diseases. In January 2018, Karyopharm announced its entry into an agreement with Biogen to acquire Karyopharm’s investigational oral SINE compound KPT-350 targeting certain neurological and neurodegenerative conditions, including amyotrophic lateral sclerosis (ALS). The transaction carries a total deal value of up to $217 million, plus royalties.

Exclusive License Agreement with Ono Pharmaceutical Co., Ltd. (Ono) to Develop and Commercialize Selinexor and Eltanexor in Japan and Other Countries in Asia. In October 2017, Karyopharm announced its entry into an exclusive license agreement with Ono for the development and commercialization of selinexor and eltanexor. The agreement includes the development of selinexor and eltanexor for the diagnosis, treatment and/or prevention of all human oncology indications in Japan, South Korea, Taiwan, Hong Kong, and the ASEAN countries (the Territory). The transaction carries a total deal value of up to $193.0 million based on the exchange rate on the effective date of the license agreement plus royalties. Karyopharm retains all rights to selinexor and eltanexor outside the Territory.
Selinexor in Multiple Myeloma

Ongoing Phase 2b STORM Study Expansion in Patients with Penta-refractory MM. Karyopharm expects to report top-line data from the expanded STORM study cohort at the end of April 2018, and, assuming a positive outcome, intends to use the data from this study to support a request for accelerated approval from the FDA and conditional approval from the EMA for oral selinexor for penta-refractory MM. The Phase 2b STORM study was previously expanded to include 122 additional patients with penta-refractory MM.

Pivotal Phase 3 BOSTON Study Underway. Karyopharm’s pivotal, randomized Phase 3 BOSTON (Bortezomib, Selinexor and dexamethasone) study is now underway and enrolling patients in 14 countries globally. BOSTON is designed to evaluate 100mg of selinexor dosed once weekly in combination with the proteasome inhibitor Velcade (once weekly) and dexamethasone (SVd), compared to standard twice weekly Velcade and low-dose dexamethasone (Vd) in patients with MM who have had one to three prior lines of therapy. The primary endpoints of the study are progression free survival and overall response rate. Both the trial design and endpoints have been agreed to by the FDA and the EMA as acceptable to support an application for approval. The Company expects to enroll approximately 360 patients at over 100 clinical sites internationally and is expecting completion of enrollment in 2018, with top-line data anticipated in 2019.

Positive Phase 1b/2 STOMP Data Presented at ASH (Free ASH Whitepaper) 2017. Data presentations featuring clinical results from four treatment arms of the ongoing Phase 1b/2 STOMP study evaluating selinexor in combination with standard therapies for the treatment of patients with MM were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2017 Annual Meeting (ASH 2017). Collectively, the STOMP study data presented at ASH (Free ASH Whitepaper) 2017 continue to provide evidence of tolerability and robust anti-myeloma activity when selinexor is combined with the currently available standard myeloma therapies, including proteasome inhibitors including Velcade, immunomodulatory drugs and anti-CD38 monoclonal antibodies. Additional treatment arms with selinexor in patients with newly diagnosed disease in combination with lenalidomide, and in combination with the proteasome inhibitor Kyprolis (carfilzomib) have been added.
Selinexor in Diffuse Large B-Cell Lymphoma

Ongoing Phase 2b SADAL Study in DLBCL. Karyopharm is also investigating oral selinexor as a single-agent for the treatment of patients with relapsed or refractory DLBCL. The SADAL study is expected to enroll up to a total of 130 patients in the single-arm cohort evaluating single-agent selinexor dosed 60mg twice weekly in patients with two or more lines of prior therapy. Karyopharm plans to report top-line results by the end of 2018, and assuming a positive outcome, the Company intends to use the data from the SADAL study to support a request for accelerated approval from the FDA and conditional approval from the EMA for oral selinexor in this relapsed/refractory DLBCL patient population.
Selinexor in Solid Tumors

Phase 3 Portion of the Phase 2/3 SEAL Study in Liposarcoma Underway. Karyopharm previously reported a successful outcome from the 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. The Phase 3 portion is underway and, assuming a positive outcome on the primary end point of progression free survival, the Company intends to use the data from the Phase 2/3 SEAL study to support a New Drug Application in the U.S. and a Marketing Authorization Application (MAA) in Europe for oral selinexor as a potential new treatment for patients with advanced unresectable dedifferentiated liposarcoma. Top-line data from the Phase 3 portion of the SEAL study are anticipated by the end of 2019.

Initiation of Investigator Sponsored Phase 2/3 Trial as Maintenance Therapy in Endometrial Cancer Underway. A randomized Phase 2/3 study of selinexor vs. placebo as maintenance therapy in patients with 1-2 prior platinum-based treatments for advanced endometrial cancer lead by Dr. Ignace Vergote, Head of the Department of Obstetrics and Gynaecology and Gynaecologic Oncology at the Catholic University of Leuven, Belgium, has been initiated.
Eltanexor

Positive Phase 1/2 Eltanexor Data Presented at ASH (Free ASH Whitepaper) 2017. Data from a Phase 1/2 study evaluating oral eltanexor in 34 patients with heavily pretreated MM was also presented at ASH (Free ASH Whitepaper) 2017. The data showed that eltanexor, both alone or in combination with low-dose dexamethasone, induced responses or disease control and was associated with prolonged survival. The study has been expanded to evaluate eltanexor in patients with advanced colorectal cancer (CRC), castration-resistant prostate cancer (crPC), and myelodysplastic syndrome (MDS). These are indications where selinexor and XPO1 inhibition has shown clear activity, but where the reduced side effects of eltanexor may permit more extended dosing.
Fourth Quarter and Year Ended December 31, 2017 Financial Results

Cash, cash equivalents and investments as of December 31, 2017, including restricted cash, totaled $176.4 million, compared to $175.5 million as of December 31, 2016.

For the year ended December 31, 2017, research and development expense was $107.3 million compared to $86.9 million for the year ended December 31, 2016. For the year ended December 31, 2017, general and administrative expense was $24.9 million compared to $23.9 million for the year ended December 31, 2016.

Karyopharm reported a net loss of $129.0 million, or $2.81 per share, for the year ended December 31, 2017, compared to a net loss of $109.6 million, or $2.92 per share, for the year ended December 31, 2016. Net loss includes stock-based compensation expense of $20.4 million and $22.3 million for the years ended December 31, 2017 and December 31, 2016, respectively.

For the quarter ended December 31, 2017, research and development expense was $34.8 million compared to $20.7 million for the quarter ended December 31, 2016. The increase in research and development expenses resulted primarily from increased expenses on our late stage clinical trials for selinexor and from payments of a portion of the upfront fees we received under our license agreement with Ono. For the quarter ended December 31, 2017, general and administrative expense was $6.2 million compared to $6.5 million for the quarter ended December 31, 2016. Karyopharm reported a net loss of $39.0 million, or $0.80 per share for the quarter ended December 31, 2017, compared to a net loss of $26.9 million, or $0.65 per share, for the quarter ended December 31, 2016. Net loss includes stock-based compensation expense of $4.5 million and $5.1 million for the quarters ended December 31, 2017 and December 31, 2016, respectively.

Financial Outlook

Based on current operating plans, Karyopharm expects that its existing cash, cash equivalents and investments will be sufficient to fund its operations through at least the first quarter of 2019. These plans include the continued clinical development of selinexor in the Company’s lead indications with a focus on filing an NDA with the FDA requesting accelerated approval in MM during 2018, assuming positive data from the STORM study, and preparing the commercial infrastructure for the potential launch of selinexor in the United States. Additional key milestones expected in 2018 include a potential MAA filing to the EMA requesting conditional approval for selinexor in MM, topline data from the SADAL study and completion of enrollment in the Phase 3 BOSTON study.

Conference Call Information

Karyopharm will host a conference call today, Thursday, March 15, 2018, at 8:30 a.m. Eastern Time, to discuss the fourth quarter and full year 2017 financial results, recent accomplishments, clinical developments and business plans. To access the conference call, please dial (855) 437-4406 or (484) 756-4292 (international) at least five minutes prior to the start time and refer to conference ID: 1181109. An audio recording of the call will be available under "Events & Presentations" in the "Investor" section of Karyopharm’s website, View Source, approximately two hours after the event.

On March 15, 2018 Histogenics Corporation (Histogenics) (Nasdaq:HSGX), a leader in the development of restorative cell therapies (RCTs) that may offer rapid-onset pain relief and restored function, reported its financial and operational results for the quarter and year ended December 31, 2017 (Press release, Histogenics, MAR 15, 2018, View Source;p=RssLanding&cat=news&id=2338178 [SID1234524793]).

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"We achieved multiple, significant milestones in our global development strategy for NeoCart in 2017, providing a strong foundation for additional value creation in 2018. With the completion of enrollment in the NeoCart Phase 3 clinical trial in the first half of 2017, we are on track to report top-line data from this trial and potentially submit a Biologics License Application for this novel restorative cell therapy in the third quarter of 2018. In parallel we are initiating pre-commercialization activities for the U.S. market in advance of a potential launch of NeoCart in fourth quarter of 2019, and we continue to hear positive anecdotal feedback from our investigators regarding NeoCart patients," stated Adam Gridley, President and Chief Executive Officer of Histogenics. "We also made significant progress on the international expansion of the NeoCart platform by completing formal discussions with the Japan Pharmaceuticals and Medical Devices Agency on the development and regulatory pathway for NeoCart in Japan. Our robust historical data packages and the PMDA conclusions were instrumental in our ability to complete the licensing agreement with MEDINET for the rights to develop and commercialize NeoCart in Japan."

2017 and Recent Milestones

NeoCart Clinical, Regulatory and Commercialization

Completed enrollment for NeoCart Phase 3 clinical trial: In June 2017, Histogenics enrolled the final patient for its 249-patient Phase 3 randomized, controlled clinical trial conducted against the current standard of care, microfracture. The trial is being conducted under a Special Protocol Assessment with the United States Food and Drug Administration (the FDA).

Executed licensing agreement for the development and commercialization of NeoCart in Japan with MEDINET Co., Ltd. (MEDINET): In December 2017, Histogenics entered into an agreement with MEDINET, a pioneering leader in the development and commercialization of cancer immuno-cell therapy technologies, for the development and commercialization of NeoCart for the Japanese market. The agreement included a $10 million up-front payment, potential total payments of up to $87 million in total milestones and tiered royalties on sales. MEDINET intends to initiate NeoCart clinical development in Japan in the second half of 2018, and may enter the Japanese market in 2021, if approved.

Completed formal discussions with the Japan Pharmaceuticals and Medical Devices Agency (PMDA) to establish the development/regulatory pathway for NeoCart in Japan: Histogenics successfully concluded formal discussions with the PMDA in the second quarter of 2017. Feedback from the PMDA was positive and included the determination that a 30-patient, one-year confirmatory clinical trial with Japanese patients, comparing NeoCart to microfracture, would be sufficient for applying for full Marketing and Manufacturing Authorization in Japan in conjunction with data from Histogenics’ fully enrolled U.S. Phase 3 clinical trial. Additionally, the PMDA agreed that NeoCart would be regulated as a Regenerative Medicine Product, as covered by the recently enacted laws in Japan, and that Histogenics may supply the confirmatory clinical trial from the U.S. using the current good manufacturing processes (cGMP) for NeoCart.

Confirmed significant unmet need in cartilage repair through U.S. and Japan NeoCart market research: Histogenics conducted primary market research in the U.S. and Japan with approximately 200 orthopedic and sports medicine surgeons across both markets. The findings provide support for Histogenics’ assumptions regarding the size of each market, the lack of satisfactory solutions, and confirm the need for a novel cartilage repair therapy. Surgeons noted a strong desire for a safe and effective alternative to microfracture that may potentially offer patients a more rapid recovery from pain and return to function as well as a durable treatment response.
NeoCart Data Publications and Presentations

Generated additional peer-reviewed data that may support the upcoming NeoCart regulatory submissions and highlight the potential of Histogenics’ RCT platform: The published results included analyses of the compressive properties of engineered cartilage tissue grown with chondrocytes seeded in a porous scaffold in a study titled "In Vitro Culture Increases Mechanical Stability of Human Tissue Engineered Cartilage Constructs by Prevention of Microscale Scaffold Buckling," which appeared in the peer-reviewed Journal of Biomechanics. In addition, a study appearing in the Journal of Orthopaedic Research entitled "Mechanical Properties and Structure-Function Relationships of Human Chondrocyte-Seeded Cartilage Constructs After In Vitro Culture" evaluated 3-D bioprinting of collagen and chondrocytes. These studies may support both process optimization and a potential Biologics License Application (BLA) filing for NeoCart, as well as the future development of additional product candidates based on the RCT technology platform.

Podium and poster presentations at Orthopedic Research Society (ORS) Annual Meeting: Dr. Shuichi Mizuno, Ph.D., a scientific founder of NeoCart, Assistant Professor, Orthopedic Surgery, Brigham and Women’s Hospital (BWH), and Harvard Medical School, delivered a podium presentation on NeoCart and Histogenics’ RCT technology platform at the ORS Annual Meeting on March 10, 2018. In addition, three additional poster presentations on NeoCart were presented during the meeting. Data presented on these posters are available here.
Corporate

Enhanced executive team ahead of potential approval and commercialization of NeoCart: In October 2017, Histogenics promoted Stephen Kennedy from Chief Technology Officer to Executive Vice President & Chief Operating Officer. In June 2017, Donald Haut was appointed Chief Business Officer. Both individuals possess strong professional experience that will be instrumental as Histogenics prepares for potential NeoCart commercial manufacturing and launch.

Completed registered direct financing: In January 2018, Histogenics raised net proceeds of $5.9 million dollars from a registered direct offering of its common stock. The proceeds from the offering provided an important source of additional funding and flexibility in advance of a potential NeoCart BLA filing.
2018 Corporate Objectives

Report NeoCart top-line Phase 3 data and submit BLA: Assuming positive results from the report of top-line superiority data from the NeoCart Phase 3 clinical trial in the third quarter of 2018, Histogenics remains positioned to submit a BLA with the FDA thereafter in the third quarter of 2018.

Continue advancement of NeoCart U.S. commercialization strategy: In advance of potential FDA approval of NeoCart, Histogenics intends to continue to prepare for a potential NeoCart launch in the U.S., including the assembly of a leading Clinical Advisory Board, the further development of marketing and reimbursement strategies and the initial development of sales and medical science liaison territories.

Leverage collaborations to generate and publish additional data to support BLA and foreign regulatory filings and potential U.S. commercialization of NeoCart: Histogenics expects to continue to generate data from its collaborations with BWH, Cornell University (Cornell) and Intrexon Corporation (Intrexon). Anticipated presentations and publications in 2018 include additional biomechanical and three-dimensional printing data from the collaboration with Cornell, the use of chondrocytes to develop new products to treat additional soft-tissue and musculoskeletal-related disorders from the collaboration with BWH and proof-of-concept data from studies combining Intrexon’s induced Pluripotent Stem Cell (iPSC) technology and Histogenics’ NeoCart platform to manufacture next generation, NeoCart restorative cell therapies using iPSC-derived chondrocytes.

Secure additional manufacturing capacity: Subject to positive top-line data from the NeoCart Phase 3 clinical trial, Histogenics intends to initiate the design and buildout of additional space to support expected increased commercial manufacturing requirements in future years following the initial launch of NeoCart.

Support MEDINETS’ Japan clinical trial and regulatory activities: Histogenics is working closely with MEDINET on the development of NeoCart for the Japanese market. Specifically, the companies intend to work on the preparation of a clinical trial notification to support the planned NeoCart Phase 3 clinical trial in Japan in the second half of 2018. In addition, Histogenics intends to continue to explore additional licensing opportunities for NeoCart outside of North America.
Financial Results for the Year Ended December 31, 2017

Histogenics’ loss from operations was $(25.0) million for the year ended December 31, 2017, compared to $(30.3) million for the year ended December 31, 2016. The decrease in operating loss was driven by a reduction in research and development expenses and partially offset by an increase in general and administrative expenses.

Research and development expenses were $15.6 million for the year ended December 31, 2017, compared to $21.6 million for the year ended December 31, 2016. The decrease was primarily due to decreases in collaboration, consulting and temporary labor expenses, clinical trial-related costs, personnel-related expenses and repairs and maintenance costs concurrent with the wind up of enrollment in our NeoCart Phase 3 clinical trial. General and administrative expenses were $9.4 million for the year ended December 31, 2017, compared to $8.5 million for the year ended December 31, 2016. The increase was primarily due to increased activities related to potential commercialization of NeoCart and was driven by increases in personnel-related costs, professional fees and facility-related and stock-based compensation expenses.

Basic net loss attributable to common stockholders was $(22.5) million for the year ended December 31, 2017, or $(0.99) per share, compared to $(13.9) million, or $(0.97) per share, for the year ended December 31, 2016. The increase in basic net loss attributable to common stockholders is attributable to the conversion into common stock in 2017 of a significant portion of the convertible preferred stock issued in connection with the 2016 private placement and changes in the fair value of the warrants issued in connection with the 2016 private placement, both of which were offset by a reduction in operating expenses in 2017 relative to 2016. Diluted net loss attributable to common stockholders was $(22.5) million for the year ended December 31, 2017, or $(0.99) per share, compared to $(31.4) million, or $(2.18) per share, for the year ended December 31, 2016. The difference in diluted net loss per share is primarily due to a reduction in operating expenses.

At December 31, 2017, Histogenics had cash, cash equivalents and marketable securities of $8.0 million, compared to $31.9 million at December 31, 2016. Cash at December 31, 2017 excludes approximately $9.0 million net of expenses received in January 2018 in connection with the licensing agreement entered into with MEDINET in December 2017 and $5.9 in net proceeds from the registered direct offering completed in January 2018.

Histogenics expects total operating expenses of between $29 million and $31 million for the year ending December 31, 2018 and believes its current cash position will be sufficient to fund its operations into the fourth quarter of 2018.

Conference Call and Webcast Information

Histogenics management will host a conference call on Thursday, March 15, 2018 at 8:30 a.m. EDT. A question-and-answer session will follow Histogenics’ remarks. To participate on the live call, please dial (877) 930-8064 (domestic) or (253) 336-8040 (international) and provide the conference ID "7394538" five to ten minutes before the start of the call.

To access a live audio webcast of the presentation on the "Investor Relations" page of the Histogenics website, please click here. A replay of the webcast will be archived on Histogenics’ website for approximately 45 days following the presentation.

On March 15, 2018 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer,reported financial results for the fourth quarter and year ended December 31, 2017, as well as provided a business update (Press release, Adaptimmune, MAR 15, 2018, View Source;p=RssLanding&cat=news&id=2338214 [SID1234524788]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Clinical momentum
There have been three partial responses (two confirmed and one to be confirmed), and one stable disease in the first four patients dosed with NY‑ESO SPEAR T-cells in a second solid tumor: myxoid/ round cell liposarcoma (MRCLS). A summary of these data is planned at an upcoming congress.

In addition to the NY-ESO program which has been optioned by GSK, clinical momentum continues across the company’s wholly owned programs with:

Patients enrolling in the one billion target cell dose cohort of the MAGE-A10 triple tumor study
Dosing in the initial safety cohort (100 million cells) of the MAGE-A4 "basket" study
For Adaptimmune’s wholly owned therapies, the first patients were dosed with MAGE-A10, in non-small cell lung cancer (NSCLC), and in the triple tumor study, in 2017, and initial safety results were presented in January 2018. Initial efficacy data from the MAGE-A10 pilot studies are anticipated in the second half of 2018. Initial safety data from the MAGE-A4 "basket study" (required to support dose escalation to one billion cells) is anticipated in the first half of 2018. MAGE-A4 efficacy data and initial AFP safety data are anticipated throughout the second half of 2018.

Manufacturing progress
Adaptimmune continues to make progress towards its ambition of being a fully integrated cell therapy company. Since the announcement in January 2018 that the company’s Navy Yard facility in Philadelphia was up and running to produce SPEAR T-cells for its wholly owned programs, Adaptimmune has manufactured a number of batches for patients, which have all achieved cell volumes in the range of the therapeutic doses seen with NY-ESO in synovial sarcoma.

In addition, Adaptimmune announced in January of this year that it had executed an agreement with Cell and Gene Therapy (CGT) Catapult, providing its own dedicated manufacturing space to secure vector supply for the medium term.

Adaptimmune is also in a strong financial position with a cash runway to early 2020, based on management’s current estimates.

"Today’s news that NY-ESO has achieved partial responses in a second solid tumor is further validation of our SPEAR T-cell platform. We have previously reported good responses in another solid tumor, synovial sarcoma, as well as in multiple myeloma. These data combined are powerful confirmation of the broad applicability of our SPEAR TCR T-cell platform in solid tumors," commented James Noble, Adaptimmune’s Chief Executive Officer. "When one considers the NY-ESO data, the initial safety data with MAGE-A10, our anticipated readouts for the rest of the year, our manufacturing progress, and our strong financial position, we expect 2018 will be the year we demonstrate that we have the industry-leading clinical TCR pipeline for solid tumors."

Highlights:
NY-ESO Program (partnered with GSK):
Compelling clinical data supports the potential of Adaptimmune’s TCR T-cell therapies to treat solid tumors

Myxoid/round cell liposarcoma [MRCLS]: There have been three partial responses (two confirmed and one to be confirmed), and one stable disease in the first four patients dosed with NY-ESO SPEAR T-cells in MRCLS. A separate press release was issued today with additional detail (View Source).
Synovial sarcoma: Data presented at ASCO (Free ASCO Whitepaper) and CTOS (2017) indicate that NY-ESO SPEAR T-cells continue to be generally well-tolerated with confirmed responses in all cohorts with a median projected overall survival of 120 weeks (~28 months) in Cohort 1
Data update: The synovial sarcoma and MRCLS studies will be presented at an upcoming congress
Multiple myeloma:
– Data update presented at ASH (Free ASH Whitepaper) 2017 indicate that NY-ESO SPEAR T-cells in the setting of autologous stem cell transplant (ASCT) have promising efficacy and acceptable safety in multiple myeloma patients with durable responses and long-term survival demonstrated in this refractory population
– The study of NY-ESO SPEAR T-cells in combination with KEYTRUDA in multiple myeloma is ongoing and will transition to GSK
GSK option exercise and transition:
– GSK exercized its option to exclusively license the right to research, develop, and commercialize Adaptimmune’s NY-ESO SPEAR T-cell therapy program in September 2017, providing up to $61 million (£48 million) in milestones and option fees over the course of the transition period; GSK also nominated a second target, PRAME, in January 2017, which Adaptimmune will take through preclinical development.
– The transition of the NY-ESO program to GSK is well underway
Wholly Owned Programs:
2018 will be the year Adaptimmune has the opportunity to prove that the company has the industry leading clinical TCR pipeline to treat solid tumors

Continued momentum towards safety and efficacy readouts from SPEAR T-cells targeting MAGE-A10 and MAGE-A4 in multiple solid tumors throughout the second half of 2018, and initial safety data from AFP in hepatocellular carcinoma anticipated in late 2018

MAGE-A10:
– Safety: To date, no evidence of off-target toxicity in MAGE-A10 pilot studies in patients who received 100 million cells, and no reports of severe neurotoxic events similar to CAR‑T cell-related encephalopathy syndrome (CRES)1
– Triple tumor study: Announced in January of this year that the scientific review committee (SRC) recommended dose escalation to one billion transduced cells (target dose)
MAGE-A4:
– Basket study: Dosing in the pilot study of SPEAR T-cells targeting MAGE-A4 in bladder, melanoma, head & neck, ovarian, NSCLC, esophageal, and gastric cancers
AFP:
– Hepatocellular carcinoma: Study open and enrolling with initial safety data anticipated in late 2018
________________________________
1 Chimeric antigen receptor T-cell therapy – assessment and management of toxicities. Nat Rev Clin Oncol. 2017 Sep 19

Manufacturing:
Adaptimmune is building a fully integrated cell therapy company

Announced in January 2018 that the company’s Navy Yard facility in Philadelphia was up and running to produce SPEAR T-cells for its wholly owned programs
Adaptimmune has since manufactured a number of batches for patients, which have all achieved cell volumes in the range of the therapeutic doses seen with NY-ESO in synovial sarcoma
Executed an agreement with Cell and Gene Therapy (CGT) Catapult that will enable Adaptimmune to have its own dedicated vector manufacturing space in the UK
This agreement is intended to ensure vector supply for ongoing studies with all three wholly owned SPEAR T-cell therapies, MAGE-A4, MAGE-A10, and AFP
Other corporate news:
Adaptimmune is in a strong financial position to deliver success with SPEAR T-cell therapies

Funded through to early 2020 with cash and cash equivalents of $84.0 million and total liquidity2 of $208.3 million
Completed March 2017 public offering and April 2017 registered direct offering to Matrix Capital Management Company, LP, raising total net proceeds of $103.2 million
Financial Results for the three and twelve month period ended December 31, 2017

Cash / liquidity position: As of December 31, 2017, Adaptimmune had cash and cash equivalents of $84.0 million and Total Liquidity3 of $208.3 million.
Revenue: Revenue represents the upfront and milestone payments, which are recognized over the estimated period the Company delivers services to GSK. Revenue for the three and twelve months ended December 31, 2017 were $4.3 million and $37.8 million compared to $8.5 million and $14.2 million for the same periods of 2016. The increase in revenue year-on-year is primarily due to an increase in revenue amortization of $17.5 million in the third quarter resulting from a reduction in the period over which we recognize revenue as a result of GSK’s exercise of the NY‑ESO option and additional revenue amortization on milestones achieved in the year.
Research and development ("R&D") expenses: R&D expenses for the three and twelve months ended December 31, 2017 were $25.1 million and $87.4 million, compared to $16.8 million and $63.8 million for the same periods of 2016. The increase was primarily due to increased costs associated with clinical trials; costs of developing manufacturing capability in the Company’s U.S. facility and increased personnel expenses.
General and administrative ("G&A") expenses: G&A expenses for the three and twelve months ended December 31, 2017 were $8.8 million and $31.1 million, compared to $6.3 million and $23.2 million for the same periods of 2016. The increase was primarily due to increased personnel costs consistent with our planned growth an increase in costs associated with supporting and maintaining our IT infrastructure.
Net loss: Net loss attributable to holders of the Company’s ordinary shares for the three and twelve months ended December 31, 2017 was $27.3 million and $70.1 million ($(0.13) per ordinary share) compared to $15.4 million and $71.6 million ($(0.17) per ordinary share) in the same periods of 2016.
Financial Guidance
The Company believes that its existing cash and cash equivalents, short-term deposits and marketable securities will fund the Company’s current operating plan through to early 2020.
_______________________
2 Total liquidity is a non-GAAP financial measure, which is explained and reconciled to the most directly comparable financial measures prepared in accordance with GAAP below.

3 Total liquidity is a non-GAAP financial measure, which is explained and reconciled to the most directly comparable financial measures prepared in accordance with GAAP below.

Conference Call Information
The Company will host a live teleconference and webcast to provide additional details at 8:00 a.m. EDT (12:00 p.m. GMT) today, March 15, 2018. The live webcast of the conference call will be available via the events page of Adaptimmune’s corporate website at www.adaptimmune.com. An archive will be available after the call at the same address. To participate in the live conference call, if preferred, please dial 1-800-239-9838 (U.S.) or 44(0)330 336 9411 or 0800 279 7204 (United Kingdom). After placing the call, please ask to be joined into the Adaptimmune conference call and provide the confirmation code (5199507).

On March 14, 2018 Spherix Incorporated (SPEX), a technology development company committed to the fostering of innovation and monetization of intellectual property, reported a proposed registered public offering of its common stock (Press release, Spherix, MAR 14, 2018, View Source [SID1234538991]). The offering is being made on a "best efforts" basis and subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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Laidlaw & Company (UK) Ltd. is acting as exclusive placement agent for the offering.

Spherix intends to use the net proceeds from the offering, if completed, for working capital and general corporate purposes.

The shares are being offered pursuant to an effective shelf registration statement on Form S-3, as amended (File No. 333-222488), that was previously filed with the Securities and Exchange Commission (SEC) and declared effective on January 19, 2018. The shares may be offered only by means of a prospectus supplement and the accompanying base prospectus. The preliminary prospectus supplement and accompanying base prospectus related to the offering will be filed with the SEC and will be available on the SEC’s website located at View Source and may also be obtained from Laidlaw & Company (UK) Ltd., Attention: Syndicate Department, 546 Fifth Avenue, 5th Floor, New York, New York 10036, telephone (212) 953-4900, email: [email protected].

This press release shall not constitute an offer to sell, or the solicitation of an offer to buy, nor may there be any sale of these shares in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On March 14, 2018 Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage biopharmaceutical company developing multifunctional therapeutics, reported that ZW49 is the first product candidate selected for clinical development utilizing the ZymeLink antibody-drug conjugate (ADC) platform, acquired as part of the Company’s 2016 acquisition of Kairos Therapeutics (Press release, Zymeworks, MAR 14, 2018, View Source [SID1234529108]). ZW49 was developed by leveraging ZymeLink in combination with Zymeworks’ flagship Azymetric bispecific platform. The Company expects to file an Investigational New Drug (IND) application this year in order to begin clinical trials with ZW49 for patients with HER2-expressing cancers.

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ZW49 is a novel bispecific ADC targeting two distinct domains of the HER2 receptor resulting in enhanced internalization and delivery of its proprietary ZymeLink cytotoxic payload. ADCs incorporating ZymeLink have demonstrated a greater therapeutic window (range of doses that are both efficacious and tolerable) in preclinical testing than those incorporating the commonly used ADC payloads DM1 or MMAE. As a result, ZW49 exhibited superior activity when assessed against other approved HER2-targeted therapies and Zymeworks’ previous internal ADC candidate, ZW33. Consequently, the Company will advance ZW49 in lieu of ZW33. Preclinical data on ZW49 and more generally on the ZymeLink ADC platform will be presented at the annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) to be held April 2018 in Chicago. Abstracts for these preclinical data were published today.

"The data generated by ZW49 clearly supported its designation as our second product candidate for clinical evaluation," said Ali Tehrani, Ph.D., President and CEO of Zymeworks. "With the addition of the complementary ZymeLink technology, including proprietary linkers and payloads, we have been able to further leverage the power of our Azymetric platform to create a differentiated molecule that we believe has the potential for best-in-class activity and tolerability."

Zymeworks, whose protein engineering expertise and resulting therapeutic platforms have resulted in a network of global biopharmaceutical partners, is keenly focused on developing its own portfolio of product candidates. Its lead compound, ZW25, is currently being assessed in an adaptive Phase 1 clinical trial and has shown promising single-agent anti-tumor activity in patients with heavily pretreated HER2-expressing cancers that have progressed after standard of care. Zymeworks continues to accelerate the development of ZW25 and is opening several new clinical sites across North America in 2018.

"With the advancement of ZW49, we now have a portfolio of agents with the potential to address the full spectrum of patients with HER2-expressing cancers," said Diana Hausman, M.D., Chief Medical Officer of Zymeworks. "This includes those underserved patients whose tumors express lower levels of HER2 and are ineligible for treatment with HER2-targeted therapies, such as trastuzumab, pertuzumab, and T-DM1."

About ADCs

Antibody-drug conjugates are a class of anti-cancer therapies intended to precisely target tumor cells in order to avoid the significant toxicities routinely associated with cancer treatments while simultaneously improving their efficacy. An ADC is an antibody connected, or conjugated, to a small molecule drug. It has three critical components: the antibody for targeting of specific cells, the cytotoxin (or payload) being delivered to induce cancer cell death, and the linker, which connects the two components together.

About ZW49

ZW49 is a biparatopic (a bispecific antibody that can simultaneously bind two non-overlapping epitopes on a single target) anti-HER2 ADC based on the same framework as ZW25 but armed with the company’s proprietary ZymeLink cytotoxic (potent cancer-cell killing) payload. ZW49 may mediate its therapeutic effect through a combination of mechanisms, including: increased HER2 receptor-antibody clustering and internalization leading to toxin-mediated cytotoxicity; dual HER2 signal blockade; increased binding and removal of HER2 protein from the cell surface; and potent effector function.