On November 9, 2015 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a clinical-stage pharmaceutical company, reported financial results for the third quarter 2015 and commented on recent accomplishments and clinical development plans for its pipeline of SINE-based therapeutics including selinexor, its lead product candidate (Filing, 8-K, Karyopharm, NOV 9, 2015, View Source [SID:1234508114]).

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"This has been a very busy period for Karyopharm with active enrollment across our ongoing selinexor clinical studies and new studies, primarily in combination with other anticancer agents, continuing to come on-line," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "We look forward to sharing additional data on our pipeline of first-in-class oncology therapeutics at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) 2015 annual meeting, including selinexor activity in combination regimens across hematologic malignancies."

Conference Call Information:

Karyopharm will host a conference call today, Monday, November 9, 2015, at 8:30 a.m. Eastern Time, to discuss the third quarter 2015 financial results, recent accomplishments and clinical developments plans. To access the conference call, please dial (855) 437-4406 (US) or (484) 756-4292 (international) at least five minutes prior to the start time and refer to conference ID: 69164993. 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.
Clinical Development Plans:

• Based on striking preclinical synergy in animal models of myeloma, Karyopharm initiated a multi-center, Phase 1b/2 clinical study of selinexor called STOMP ("Selinexor and Backbone Treatments of Multiple Myeloma Patients") with support from Myeloma Canada. In this multi-arm study, Karyopharm is evaluating the combination of selinexor and low dose dexamethasone with backbone therapies bortezomib, pomalidomide or lenalidomide in patients with previously treated multiple myeloma. Approximately 220 patients with multiple myeloma will be enrolled in this study with preliminary top-line data anticipated in 2017. Selinexor and low dose dexamethasone are already being combined with carfilzomib in an Investigator-sponsored trial (IST), where promising preliminary data were presented at the ASH (Free ASH Whitepaper) 2014 annual meeting and will be updated with additional patient data at the ASH (Free ASH Whitepaper) 2015 annual meeting.

• Karyopharm is actively enrolling patients in four later phase clinical studies evaluating single-agent selinexor: one in older patients with relapsed/refractory acute myeloid leukemia (SOPRA study), the second in patients with relapsed/refractory diffuse large B-cell lymphoma (SADAL study), the third in patients with multiple myeloma (STORM study) and the fourth in patients with Richter’s transformation (SIRRT study). Interim data are expected from the SOPRA and STORM studies in the middle of 2016. Preliminary top-line data from the SOPRA and SADAL studies are anticipated in the fourth quarter of 2016.

Targeting Disease at the Nuclear Pore

• Karyopharm is currently conducting company-sponsored trials of single-agent selinexor in three solid tumor indications including heavily pretreated patients with gynecologic malignancies (SIGN study), recurrent glioblastoma multiforme (KING study) and hormone-refractory prostate cancer (SHIP study). Based on promising data observed in a Phase 1 study, a randomized, blinded Phase 2/3 trial of selinexor versus placebo in liposarcoma (SEAL study) is planned to commence in the fourth quarter of 2015.

• In addition, a number of ISTs or company-sponsored trials evaluating the potential of selinexor in combination with either chemotherapy or targeted agents are currently ongoing or planned.

• Based on promising preclinical data, Karyopharm filed an Investigational New Drug (IND) application with the Food and Drug Administration (FDA) for KPT-8602 and, pending review, plans to initiate a clinical study in multiple myeloma in early 2016.

• Karyopharm also plans to file an IND for its first-in-class, oral PAK4 Allosteric Modulator, KPT-9274, and initiate clinical development in patients with heavily pretreated solid tumors or lymphoma in the first half of 2016.
Scientific Presentations and Publications:

• Five oral presentations and twelve poster presentations describing Karyopharm’s pipeline of first-in-class oncology therapeutics were accepted for presentation at the upcoming 57th Annual American Society of Hematology (ASH) (Free ASH Whitepaper) 2015 meeting being held December 5 – 8, 2015 in Orlando, Florida. The accepted abstracts include:

• Clinical and preclinical data demonstrating the promising activity of selinexor (KPT-330), Karyopharm’s most advanced, novel, oral Selective Inhibitor of Nuclear Export/SINE compound, in combination with other anti-cancer agents;

• Preclinical data on KPT-8602, a second generation SINE compound in early-stage development with the potential for distinct pharmaceutical characteristics; and

• Preclinical data on KPT-9274, a first-in-class oral PAK4 Allosteric Modulator.

• Preclinical data demonstrating the anti-tumor benefits of combining selinexor with immunotherapy in aggressive melanoma models were presented at the Society for Immunotherapy Cancer (SITC) (Free SITC Whitepaper) 2015 Annual Meeting held November 4 – 8, 2015 in National Harbor, Maryland. In an oral presentation entitled "Selinexor, a Selective Inhibitor of Nuclear Export (SINE), enhanced activity in combination with PD-1/PD-L1 blockade in syngeneic murine models of colon cancer and melanoma" Karyopharm researchers and collaborators at The Ohio State University demonstrated that the combination of selinexor with PD-1 or PDL-1 immune checkpoint inhibitors exerts considerable anti-tumor and immune-stimulating activity in an aggressive murine melanoma model.

• Data demonstrating the beneficial pharmacological effects of SINE-based compounds in neurodegenerative models, including Amyotrophic Lateral Sclerosis (ALS), were recently published in the journal Nature and presented at the American Neurological Association (ANA) and the Society for Neuroscience (SfN) meetings. These data confirm that nuclear transport is disrupted by a common gene mutation found in ALS and describe the neuroprotective effects of SINE compounds, similar to the neuroprotective effects previously observed in Multiple Sclerosis (MS). Karyopharm’s SINE compound research efforts in ALS are being supported entirely by collaborator grant funding, with MS research supported by the National Multiple Sclerosis Society. Given the tremendous unmet need for new treatments for ALS and MS, Karyopharm is advancing its oral SINE compound KPT-350 for these indications.

Targeting Disease at the Nuclear Pore

Third Quarter September 30, 2015 Financial Results
Cash, cash equivalents and investments as of September 30, 2015, including restricted cash, totaled $230.2 million, compared to $256.0 million as of June 30, 2015.

For the quarter ended September 30, 2015, research and development expense was $25.9 million compared to $16.0 million for the quarter ended September 30, 2014. For the quarter ended September 30, 2015, general and administrative expense was $4.8 million compared to $3.8 million for the quarter ended September 30, 2014. The increase in research and development expense resulted primarily from the increase in expenses related to the continued clinical development of selinexor. The increase in general and administrative expense resulted primarily from the costs of being a public company and an increase in stock-based compensation.

Karyopharm reported a net loss of $30.4 million, or $0.85 per share, for the quarter ended September 30, 2015, compared to a net loss of $19.7 million, or $0.61 per share, for the quarter ended September 30, 2014. Net loss includes stock-based compensation expense of $3.5 million and $2.9 million for the quarters ended September 30, 2015 and September 30, 2014, respectively.

Financial Outlook
Based on current operating plans, Karyopharm expects that its existing cash and cash equivalents will fund its research and development programs and operations into 2018, including moving the four later-stage clinical studies to their next data inflection points. Karyopharm expects to end 2015 with greater than $200 million in cash, cash equivalents and investments.

On November 9, 2015 Foundation Medicine, Inc. (NASDAQ:FMI) reported that the company and its collaborators will present three oral and four poster presentations at the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place December 5 – 8, 2015 in Orlando, Florida (Press release, Foundation Medicine, NOV 9, 2015, View Source [SID:1234508109]). Collectively, the presentations will focus on the application of FoundationOne Heme to identify druggable genomic alterations, inform personalized treatment strategies and improve clinical outcomes across a broad range of sarcomas and hematologic malignancies.

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FoundationOne Heme is a comprehensive genomic profile that analyzes DNA in 405 genes and RNA in 265 genes that are most commonly altered in hematologic malignancies and sarcomas. The assay provides oncologists and pathologists with clinically relevant genomic alterations to guide treatment options for patients based on the genomic profile of their cancer.

The schedule for oral presentations by Foundation Medicine and/or its collaborators is as follows:

Session Date & Time: Saturday, December 5, 2015, from 12:00-1:30 p.m. ET
Presentation Time: 12:45 p.m. ET
Title: Genomic and Proteomic Analysis of Primary Chemoresistance and Induction Failure in Acute Myeloid Leukemia
Publication Number: 88
Location: Tangerine 3 (WF3-4), Level 2
Session: 617 – Acute Myeloid Leukemia: Biology, Cytogenetics and Molecular Markers in Diagnosis and Prognosis: Omics-based Approaches for the Identification of Novel Genetic Modalities in AML
Presenter: Fiona Brown, Ph.D., research fellow, Memorial Sloan-Kettering Cancer Center
Collaborators: Memorial Sloan-Kettering Cancer Center, Dana-Farber Cancer Institute, Children’s Hospital Boston, Children’s Oncology Group, Fred Hutchinson Cancer Research Center, The University of Texas MD Anderson Cancer Center, The Ohio State University Comprehensive Cancer Center, Harvard Medical School

Session Date & Time: Sunday, December 6, 2015, from 4:30-6:00 p.m. ET
Presentation Time: 5:45 p.m. ET
Title: Comprehensive Genomic Profiling of Multiple Myeloma in the Course of Clinical Care Identifies Targetable and Prognostically Significant Genomic Alterations
Publication Number: 369
Location: W224ABEF
Session: 651 – Myeloma: Biology and Pathophysiology, Excluding Therapy: Novel Technologies to Evaluate Biology and Prognosis
Presenter: Christopher Heuck, M.D., assistant professor of medicine, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences
Collaborators: Myeloma Institute for Research and Therapy

Session Date & Time: Monday, December 7, 2015 from 7:00-8:30 a.m. ET
Presentation Time: 7:00 a.m. ET
Title: Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms
Publication Number: 481
Location: W331
Session: 635 – Myeloproliferative Syndromes: Basic Science I
Presenter: Benjamin Durham, M.D., research fellow, Memorial Sloan-Kettering Cancer Center
Collaborators: Memorial Sloan-Kettering Cancer Center

The schedule for poster presentations by Foundation Medicine and/or its collaborators is as follows:

Poster Display: Saturday, December 5, 2015 from 9:00 a.m.-7:30 p.m. ET
Poster Presentation: Saturday, December 5, 2015 from 5:30-7:30 p.m. ET
Title: Integrated DNA/RNA Profiling for Somatic Alterations in Adult B-cell ALL
Publication Number: 1422
Poster Display Location: Hall A2-A3
Poster Presentation Location: Hall A2-A3
Session: 618 – Acute Lymphoblastic Leukemia: Biology, Cytogenetics and Molecular Markers in Diagnosis and Prognosis: Poster I
Presenter: Franck Rapaport, Ph.D., computational research leader, Leukemia Center, Memorial Sloan-Kettering Cancer Center
Collaborators: Memorial Sloan-Kettering Cancer Center, Montefiore Medical Center, Mayo Clinic, University of Pennsylvania, Shaare Zedek Medical Center, Northwestern University Feinberg School of Medicine, Weill Cornell Medical College

Poster Display: Sunday, December 6, 2015 from 9:00 a.m.-8:00 p.m. ET
Poster Presentation: Sunday, December 6, 2015 from 6:00-8:00 p.m. ET
Title: Predictive and Prognostic Significance of Comprehensive Genomic Profiling in Patients with Diffuse Large B-cell Lymphoma
Publication Number: 2651
Poster Display Location: Hall A2-A3
Poster Presentation Location: Hall A2-A3
Session: 622 – Non-Hodgkin Lymphoma: Biology, Excluding Therapy: Poster II
Presenter: Jie He, senior manager, computational biology analysis, Foundation Medicine

Poster Display: Sunday, December 6, 2015 from 9:00 a.m.-8:00 p.m. ET
Poster Presentation: Sunday, December 6, 2015 from 6:00-8:00 p.m. ET
Title: Defining the Incidence and Clinical Impact of Genomic Alterations Across Different Histologic Types of Lymphoma Using a Clinically Validated Comprehensive Targeted Sequencing Assay
Publication Number: 2668
Poster Display Location: Hall A2-A3
Poster Presentation Location: Hall A2-A3
Session: 622 – Non-Hodgkin Lymphoma: Biology, Excluding Therapy: Poster III
Presenter: Connie Lee Batlevi, M.D., Ph.D., hematology/oncology fellow, Memorial Sloan-Kettering Cancer Center
Collaborators: Memorial Sloan-Kettering Cancer Center

Poster Display: Monday, December 7, 2015 from 10:00 a.m.-8:00 p.m. ET
Poster Presentation: Monday, December 7, 2015 from 6:00-8:00 p.m. ET
Title: Comprehensive Genomic Profiling (CGP) of Angioimmunoblastic T-cell Lymphoma (AITL) to Prospectively Inform Diagnosis and Clinical Management
Publication Number: 3898
Poster Display Location: Hall A2-A3
Poster Presentation Location: Hall A2-A3
Session: 622 – Non-Hodgkin Lymphoma: Biology, Excluding Therapy: Poster III
Presenter: Tariq Mughal, M.D., vice president, medical affairs, Foundation Medicine
Collaborators: Memorial Sloan-Kettering Cancer Center, Tufts University Medical Center

On November 9, 2015 Epizyme, Inc. (NASDAQ:EPZM), a clinical stage biopharmaceutical company creating novel epigenetic therapies for cancer patients, reported business highlights and operating and financial results for the third quarter of 2015 (Press release, Epizyme, NOV 9, 2015, View Source [SID:1234508107]).

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"Epizyme is well-positioned, with tazemetostat achieving proof of concept in both hematological malignancies and genetically defined solid tumors, while demonstrating an acceptable safety profile," said Robert Bazemore, President and Chief Executive Officer, Epizyme. "Epizyme is executing on our strategic goal of bringing tazemetostat to patients as quickly as possible, and we are operating from a sound financial position. Our vision is to build Epizyme into a multi-product oncology company bringing targeted epigenetic therapies to patients."

Program Summaries

Tazemetostat:

In 2015, proof of concept was achieved in patients with relapsed or refractory B-cell Non-Hodgkin Lymphoma (NHL) and in patients with advanced solid tumors. Interim data from NHL patients enrolled in an ongoing phase 1 study were presented at the International Conference on Malignant Lymphoma meeting in June 2015 showing a 60 percent response rate in the 15 evaluable NHL patients. Data from the solid tumor patients from the same study were presented at the European Cancer Congress meeting in September 2015 reporting a 55 percent disease control rate in the nine patients with INI1-negative or SMARCA4-negative tumors who were treated at or above the recommended phase 2 dose of 800 mg orally administered twice daily. In these presentations of interim data from the ongoing phase 1 study, Epizyme reported that tazemetostat had an acceptable safety profile.

Epizyme is currently conducting a registration-supporting 5-arm phase 2 clinical study of tazemetostat as a monotherapy in patients with relapsed or refractory B-cell NHL, prospectively stratified by cell of origin and EZH2 mutational status. Epizyme expects to enroll approximately 150 patients in this study and to present interim data from the study at a medical conference by mid-2016.

Epizyme also plans to initiate two registration-supporting clinical trials in patients with INI1-negative tumors or synovial sarcoma, including a registration-supporting phase 2 study of tazemetostat in adult patients, and a proof-of-concept phase 1 trial in pediatric patients, both of which are on track to begin in the fourth quarter of 2015.

In the first half of 2016, Epizyme plans to initiate additional clinical evaluations of tazemetostat as a combination therapy, including a phase 1/2 study with R-CHOP in front-line high-risk patients with diffuse large B-cell lymphoma and a combination study with a B-cell signaling agent or immuno-oncology agent in B-cell lymphoma.

Pinometostat:

A dose-escalation study of pinometostat in pediatric patients with MLL-r acute leukemia is ongoing and enrollment in the dose escalation cohorts is expected to complete in the fourth quarter of 2015. Epizyme anticipates presenting final study results after all patients conclude treatment and related data analyses are complete.

Epizyme and Celgene are exploring the potential clinical development of pinometostat in combination with other agents based on encouraging preclinical data.

Third Quarter 2015 Financial Results

Collaboration Revenue: Collaboration revenue was $0.4 million in the third quarter of 2015 and $2.0 million for the nine months ended September 30, 2015 compared with $8.2 million and $31.1 million in the comparable periods of 2014. The decrease in collaboration revenue primarily reflects the completion of a significant portion of our performance obligations under our collaborations during 2014 and achievement of a $3.0 million milestone under our agreement with GlaxoSmithKline during 2014. We expect to recognize an additional $2.4 million of deferred revenue related to the Celgene agreement through December 31, 2016 as we complete our pinometostat phase 1 clinical trials.

R&D Expenses: Research and development expenses were $16.8 million for the third quarter 2015 and $94.4 million for the nine months ended September 30, 2015 compared to $22.2 million and $55.1 million for the comparable periods of 2014. Costs related to the expansion of tazemetostat clinical trials and related EZH2 activities and the $40.0 million upfront payment to Eisai in the first quarter of 2015 were partially offset by reductions in external spending on pinometostat and discovery and preclinical programs during the nine months ended September 30, 2015 compared to the same period of the prior year. Epizyme expects development expenses will continue to increase in 2015 as compared to 2014 since the Company is now solely responsible for funding tazemetostat clinical trials and related development costs outside of Japan. These increased expenses are likely to be partially offset by decreases in spending for pinometostat.

G&A Expenses: General and administrative expenses were $6.7 million for the third quarter of 2015 and $17.9 million for the nine months ended September 30, 2015 compared with $5.7 million and $15.9 million in the comparable periods in 2014. The increase in G&A expense was primarily related to higher personnel-related expenses and an increase in patent filings and related professional fees.

Net Loss: Net loss was $23.1 million in the third quarter 2015 and $110.2 million for the nine months ended September 30, 2015 compared with $19.7 million and $40.0 million in the comparable periods in 2014.

Cash and Cash Equivalents: Cash and cash equivalents as of September 30, 2015 were $229.9 million, compared with $190.1 million as of December 31, 2014. Epizyme’s follow-on public offering in March 2015 raised $117.0 million in proceeds before expenses and the exercise of the underwriters’ over-allotment option provided an additional $13.7 million in proceeds before expenses. The company received an upfront payment of $10.0 million under the amended and restated collaboration and license agreement with Celgene in July 2015. The company expects that, based on its current operating plan, cash and cash equivalents will be sufficient to fund its operating expenses and capital expenditure requirements through at least the end of the second quarter of 2017.

Shares Outstanding: Shares outstanding as of September 30, 2015 were 41.7 million. Weighted average shares outstanding were 41.5 million and 39.2 million for the three and nine months ended September 30, 2015 respectively and 33.7 million and 32.6 million for the comparable periods in 2014.

Conference Call Information

Epizyme will host a conference call and live audio webcast today at 8:00 a.m. ET to discuss third quarter 2015 financial results and provide a corporate update. To participate in the conference call, please dial (877) 844-6886 (domestic) or (970) 315-0315 (international) and refer to conference ID 67279629. The live webcast can be accessed under "Events and Presentations" in the Investor Relations section of the Company’s website at www.epizyme.com

The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

About Epizyme, Inc.

Epizyme, Inc. is a clinical-stage biopharmaceutical company creating novel epigenetic therapeutics for cancer patients. Epizyme has built a proprietary product platform that the Company uses to create small molecule inhibitors of chromatin modifying proteins (CMPs), such as histone methyltransferases or HMTs. CMPs are part of the system of gene regulation, referred to as epigenetics, that controls gene expression. Genetic alterations can result in changes to the activity of CMPs, making them oncogenic (cancer-causing). By focusing on the genetic drivers of cancers, Epizyme’s targeted science seeks to match the right medicines with the right patients.

For more information, visit www.epizyme.com and connect with us on Twitter at @EpizymeRx.

About EZH2 in Cancer

EZH2 is a histone methyltransferase that is increasingly understood to play a potentially oncogenic role in a number of cancers. These include Non-Hodgkin Lymphoma, rhabdoid tumors and other INI1-deficient cancers such as epithelioid sarcomas and synovial sarcoma as well as a range of other solid tumors.

About Tazemetostat

Epizyme is developing tazemetostat for the treatment of patients with Non-Hodgkin Lymphoma and patients with INI1-deficient solid tumors. Tazemetostat is a first-in-class small molecule inhibitor of EZH2 created by Epizyme using its proprietary product platform. In many human cancers, aberrant EZH2 enzyme activity results in misregulation of genes that control cell proliferation resulting in the rapid and unconstrained growth of tumor cells. Tazemetostat is the WHO International Non-Proprietary Name (INN) for EPZ-6438.

Additional information about this program, including clinical trial information, may be found here: View Source

About Pinometostat

Epizyme is developing pinometostat, a small molecule inhibitor of DOT1L created with Epizyme’s proprietary product platform, for the treatment of patients with acute leukemia in which the MLL gene is rearranged due to a chromosomal translocation (MLL-r). Due to these rearrangements, DOT1L is misregulated, resulting in the increased expression of genes causing leukemia. Pinometostat is the WHO International Non-Proprietary Name (INN) for compound EPZ-5676.

Epizyme believes that pinometostat was the first HMT inhibitor to enter human clinical development. Epizyme is currently conducting a phase 1 study of pinometostat in pediatric patients with rearrangements of the MLL gene. Additional information about this ongoing phase 1 study can be found here:

View Source

Pinometostat has been granted orphan drug designation for the treatment of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) by the Food and Drug Administration in the U.S. and by the European Commission in Europe.

Epizyme retains all U.S. rights to pinometostat and has granted Celgene an exclusive license to pinometostat outside of the U.S.

On November 09, 2015 Cyclacel Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP) ("Cyclacel" or the "Company"), reported the presentation of preclinical data demonstrating the mechanistic rationale for the development of CYC065 in targeted solid tumors and leukemias (Press release, Cyclacel, NOV 9, 2015, View Source [SID:1234508106]). CYC065 is a highly-selective, second-generation cyclin dependent kinase (CDK) inhibitor targeting CDK2- and CDK9-dependent tumors. The data were presented at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), taking place November 5-9, 2015, in Boston.

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"Through our understanding of the mechanism of action of CYC065 we have identified CDK2- and CDK9-dependent tumors against which CYC065 is predicted to have activity," said Spiro Rombotis, Cyclacel’s President and Chief Executive Officer. "These cancer types include hematological cancers, such as MLL-rearranged (MLLr) leukemias, MYC-driven lymphomas or solid tumors, and also cancers in which Cyclin E amplification is observed, such as drug resistant and poor prognosis breast and uterine cancers. In addition, we have identified approved and investigational anticancer agents, including our own sapacitabine, which exhibit a synergistic effect when combined with CYC065. A first-in-human, Phase 1 clinical trial with CYC065 has commenced and we look forward to reporting data from this study."

Data presented at AACR (Free AACR Whitepaper)-NCI-EORTC (Poster no. B182) demonstrated the mechanistic rationale for clinical development of CYC065 in oncology. Relevant solid tumor and hematologic malignancies were identified, including those with amplification or overexpression of Cyclin E (the partner of CDK2), those driven by CDK9-dependent oncogenic and leukemogenic pathways, such as acute leukemias driven by MLLr and MYC overexpressing tumors. Clinically relevant synergistic combinations were identified and the mechanism of action of CYC065 as a single agent elucidated. The anticancer activity of CYC065 was evaluated in in vitro assays of human acute myelogenous leukemia (AML) and triple negative breast cancer (TNBC) cell lines to demonstrate the pro-apoptotic mechanism of CYC065 and determinants of cellular sensitivity. CYC065 induced rapid apoptosis by inhibition of expression of CDK9-dependent oncogenic transcripts, including MCL-1 and MYC. CYC065’s potent anticancer activity was confirmed in AML xenograft animal models.

CYC065 was highly synergistic in combination with Bcl-2 inhibitors, such as venetoclax (ABT-199/GDC-0199), in both AML and acute lymphoblastic leukemias. CYC065 was also synergistic in combination with Cyclacel’s sapacitabine in breast cancer cell lines, as was the case with seliciclib, Cyclacel’s first generation CDK2/9 inhibitor.

An oral regimen of seliciclib and sapacitabine is being evaluated in an on-going Phase 1 study of patients with Homologous Recombination (HR) repair-deficient breast, ovarian and pancreatic cancers, including BRCA positive tumors. CYC065 is in a first-in-human, Phase 1 clinical trial.

On November 9, 2015 AVEO Oncology (NASDAQ:AVEO) reported financial results for the third quarter ended September 30, 2015 and provided a business update (Press release, AVEO, NOV 9, 2015, View Source;p=RssLanding&cat=news&id=2110273 [SID:1234508102]).

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"We completed partnerships for two of AVEO’s lead programs in the third quarter in addition to making progress toward our proposed plans to submit a European Marketing Authorization Application (MAA) for tivozanib in renal cancer and initiate a pivotal study in this indication in the U.S.," said Michael Bailey, president and chief executive officer. "As we work through recently initiated discussions with the SEC, we remain focused on executing against our goals through the balance of the year, including exploring potential partnership opportunities for tivozanib in Europe, while maintaining our very lean organization."

Prior to the submission of an MAA filing with the European Medicines Agency, the Company is seeking to complete a partnership agreement for tivozanib in Europe. If a partnership is completed, in order to provide a potential partner with the opportunity to submit the application on its own behalf, AVEO now anticipates that a submission would take place in the first quarter of 2016. Furthermore, assuming the availability of financial resources from this or other activities, the Company also now expects to initiate its Phase 3 U.S. pivotal study of tivozanib in patients with renal cancer early in the first quarter of 2016.

AVEO also announced today that the staff of the Securities and Exchange Commission and the Company recently entered into discussions for the settlement of potential claims that the Commission may bring against the Company asserting that the Company previously violated federal securities laws by omitting to disclose to investors a recommendation made to the Company by the U.S. Food and Drug Administration in May 2012. While the Company has commenced such discussions, it cannot predict their outcome, nor can it provide assurance that the Company will be able to resolve any potential claims of the Commission or that any potential settlement will not have a material adverse impact on the Company’s proposed plans or its financial position or results of operations.

Recent Highlights

Announced Exclusive Worldwide License Agreement for the Development and Commercialization of AV-380 and Related Antibodies. In August, AVEO announced an exclusive, worldwide license agreement with Novartis for the development and commercialization of AVEO’s first-in-class, potent, humanized inhibitory antibody targeting growth differentiation factor 15 (GDF15), AV-380, and related antibodies, including modified or derivative forms of any such antibody (the "Product"). Under terms of the agreement, AVEO has received an upfront payment of $15 million. Additionally, AVEO is eligible to receive $3.45 million in inventory reimbursement, and clinical, regulatory and sales-based milestone payments totaling $308 million, assuming successful advancement of the Product. AVEO will also be eligible to receive tiered royalties on product sales ranging from high single digits to a low double-digit. Novartis is responsible for all clinical development, manufacturing and commercialization activities and costs associated with the Product.

Announced Exclusive Licensing Agreement with Pharmstandard for Tivozanib in Russia, Ukraine and CIS. In August, AVEO announced that it had entered into an exclusive license agreement with a subsidiary of Pharmstandard Group for the development, manufacturing and commercialization of tivozanib in the territories of Russia, Ukraine and the Commonwealth of Independent States, for all indications excluding non-oncology ocular conditions. Under the terms of the agreement, AVEO has received $1 million in an upfront payment and Pharmstandard is obligated to pay AVEO an additional $0.5 million upon the registration of the agreement with Federal Services for Intellectual Property in Russia. AVEO is also eligible to receive up to $7.5 million in connection with the first marketing authorization of tivozanib in Russia, $3.0 million for each additional approved indication thereafter and a high single-digit royalty on net sales in the above mentioned territories. Pharmstandard will be responsible for all activities and costs associated with the further development, regulatory filings, health services and commercialization of tivozanib in the specified territories. A percentage of all upfront, milestone and royalty payments received by AVEO are due to Kyowa Hakko Kirin as a sublicensing fee.

Third Quarter 2015 Financial Highlights

AVEO ended Q3 2015 with $37.2 million in cash, cash equivalents and marketable securities.

Total collaboration revenue was approximately $15.2 million compared with $0.9 million for Q3 2014. The increase was primarily due to $15.0 million in revenue recognized in connection with the Company’s out-licensing agreement with Novartis, which was executed in August 2015.

Research and development (R&D) expense was $4.5 million compared with $8.5 million for Q3 2014. The decrease in R&D expense was primarily due to a reduction in personnel-related expenses following AVEO’s January 2015 strategic restructuring, the reduction of the Company’s leased facilities, as well as a decrease in external clinical trial and consulting costs associated with decreased clinical development activity and AV-380 preclinical development activity. This is offset by a $1.5 million increase in in-licensing expense associated with a milestone payment incurred upon signing the Company’s agreement with Novartis.

General and administrative (G&A) expense was $2.2 million compared with $5.1 million for Q3 2014. The decrease in G&A expense was primarily due to a reduction in external legal costs associated with various ongoing legal matters and a decrease in employee compensation, facilities and IT costs following the Company’s January 2015 restructuring and the reduction of its leased facilities.
Restructuring and lease exit expense was $0 for Q3 2015 compared with $1.4 million for Q3 2014. The expense incurred during Q3 2014 related to charges incurred following the partial termination of the Company’s 650 E. Kendall Street facility lease.

Net income for Q3 2015 was $7.9 million, or $0.14 per basic and diluted share compared with a net loss of $14.4 million or $0.28 per basic and diluted share for Q3 2014.

Updated Financial Guidance

AVEO believes that its cash resources would allow the Company to fund current operations through the fourth quarter of 2017. This estimate does not include payment of potential licensing milestones or the costs of conducting any contemplated clinical trials and assumes no milestone payments from the Company’s partners, additional funding from new partnership agreements, equity financings, debt financings or accelerated repayment thereof or further sales of equity under the Company’s ATM. In addition, AVEO cannot estimate the impact on its cash resources of a settlement of claims with the SEC. The timing and nature of activities contemplated for 2015 and thereafter will be conducted subject to the availability of sufficient financial resources.