On February 15, 2018 Cambrex Corporation (NYSE:CBM), a leading manufacturer of small molecule innovator and generic Active Pharmaceutical Ingredients (APIs), reported that Steven Klosk, President and Chief Executive Officer, will participate in a fireside chat at the 2018 RBC Capital Markets Global Healthcare Conference on February 22, 2018 at 3:05 p.m. EST in New York City (Press release, Cambrex, FEB 15, 2018, View Source [SID1234524000]).

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The live audio webcast and slide presentation can be accessed from the Cambrex website at www.cambrex.com in the Investors section under "Webcasts & Presentations", and a replay will be available for 90 days after the live event concludes.

On February 13, 2018 Advaxis, Inc. (NASDAQ:ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of cancer immunotherapies, reported that it has submitted a conditional Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for the company’s lead Lm Technology product candidate, axalimogene filolisbac, for the treatment of adult women who progress beyond first-line therapy of persistent, recurrent or metastatic carcinoma of the cervix (PRmCC) (Press release, Advaxis, FEB 15, 2018, View Source [SID1234523996]).

"The submission of the MAA represents a significant regulatory milestone for Advaxis and the ongoing development of our Lm Technology Platform," stated Anthony Lombardo, interim Chief Executive Officer of Advaxis. "The submission is based on the improvement in 12-month survival rates observed in the Phase 2 GOG-0265 study. We feel that these data support axalimogene filolisbac as a potential therapeutic option for patients living with PRmCC who are in desperate need of new treatment options beyond first-line therapy," added Lombardo.

The MAA submission is built around data from the GOG-0265 study which examined overall survival rates in 50 women and showed a 12-month overall survival rate (primary efficacy endpoint) of 38% (n=19/50) in women with PRmCC, representing a 55% improvement over an expected, model-predicted,12-month survival rate of 24.5%.2 More than 50% of treated women in this study had previously received multiple prior lines of therapy including treatment with bevacizumab and subsequently experienced progression of their disease.2

"Despite the availability of preventative measures, metastatic cervical cancer continues to be a major public health concern associated with high mortality rates within Europe," said Mansoor Mirza, M.D., Chief Oncologist at the Copenhagen University Hospital in Denmark and Medical Director of the Nordic Society of Gynaecological Oncology (NSGO). "The results from GOG-0265 are encouraging and could represent a meaningful step forward in the care of women suffering from PRmCC, which has seen very little innovation in almost 30 years."

In the GOG-0256 study, axalimogene filolisbac was generally well-tolerated with mostly Grade 1 and 2 flu-like adverse events associated with cytokine release which were managed with standard medical care. This safety profile is consistent with the ongoing clinical experience of axalimogene filolisbac across all clinical trials.

The EMA will evaluate the totality of the data, including results from GOG-0265 as well as supportive data from other clinical trials evaluating axalimogene filolisbac. In parallel with the MAA review process, the company will continue assessing partnership opportunities for the potential commercialization of axalimogene filolisbac in Europe.

The company has also decided to align and simplify its strategy by using axalimogene filolisbac exclusively in all ongoing and planned HPV-related cancer clinical trials, including the upcoming ADVANCE trial, previously planned with ADXS-DUAL. The strategic decision to harmonize all trials to axalimogene filolisbac is based on its clinical profile to date in over 250 patients, and its demonstration of similar activity in both HPV 16 and 18 subtypes in GOG-0265. The company believes that harmonizing to a single product candidate for all HPV-related programs will streamline developmental, regulatory and commercialization strategies.

About Axalimogene Filolisbac

Axalimogene filolisbac is a targeted Listeria monocytogenes (Lm)-based investigational immunotherapy that attacks HPV-associated cancers by altering a live strain of Lm bacteria to generate cancer-fighting T cells against cancer antigens while neutralizing the tumor’s natural protections that guard the tumor microenvironment from immunologic attack.

Axalimogene filolisbac has already achieved multiple regulatory milestones, including classification as an EMA advanced therapy-medicinal product for the treatment of cervical cancer, receipt of the U.S. Food and Drug Administration (FDA) Fast Track Designation as an adjuvant therapy for treating high-risk, locally advanced cervical cancer (HRLACC), receipt of a Special Protocol Assessment agreement with the FDA for the Phase 3 AIM2CERV trial, and orphan drug designations in three HPV-associated indications (PRmCC, head and neck, and anal cancer). In addition, axalimogene filolisbac will be studied in combination with nivolumab in the ADVANCE trial, a potential registrational trial for patients with PRmCC, which is planned to begin in 2018.

On February 15, 2018 Kura Oncology, Inc. (Nasdaq:KURA), a clinical-stage biopharmaceutical company focused on the development of precision medicines for oncology, reported the presentation of updated preliminary results from its Phase 2 clinical trial of its lead product candidate, tipifarnib, in patients with head and neck squamous cell carcinomas (HNSCC) with HRAS mutations (Press release, Kura Oncology, FEB 15, 2018, View Source [SID1234524150]).

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The results are being presented by Alan Ho, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center at the 2018 Multidisciplinary Head and Neck Cancers Symposium, taking place today in Scottsdale, Arizona. A copy of the poster is available online at www.kuraoncology.com.

Nine patients with HRAS mutant HNSCC had been enrolled in the Phase 2 trial as of the February 8, 2018 data cutoff date. Five out of the six evaluable patients achieved a confirmed, partial response as defined by standard RECIST criteria for an overall response rate of 83% (36-99.6%, 95%CI), including durable responses of more than 18 months in two patients. The sixth evaluable patient experienced tumor shrinkage and prolonged disease stabilization. Three additional patients were enrolled since the last update in October 2017, however, none of the three additional patients was evaluable as of the February 8th data cutoff date; two are off study and one was still too early for disease assessment.

"We continue to be very encouraged by the high level of clinical activity of tipifarnib observed in patients with HRAS mutant HNSCC," said Antonio Gualberto, M.D., Ph.D., Head of Development and Chief Medical Officer of Kura Oncology. "In addition to rapid responses in patients who do not appear to benefit from current standards-of-care, we are also seeing dramatic resolution of disfiguring and often painful lesions. We are continuing to enroll patients in the ongoing Phase 2 trial while we gather input from regulatory agencies on the design of a potential registrational trial of tipifarnib in HRAS mutant HNSCC anticipated to be initiated later this year."

All patients joined the trial upon progression from at least one line of therapy, including chemotherapy, cetuximab or immune therapy, with patients having experienced a median of two prior therapies (range, 1-4). Response rates for the three agents approved for treatment of HNSCC in the second line are in the range of 13-16%, with a median progression-free survival of approximately 2 months and a median overall survival of up to 7.5 months.

Tipifarnib was generally well-tolerated in the trial. Adverse events observed are consistent with the known safety profile of tipifarnib.

In September 2017, Kura announced that the Phase 2 trial in HRAS mutant HNSCC had achieved its primary efficacy endpoint prior to the completion of enrollment. The trial protocol required four confirmed, partial responses, per RECIST 1.1 criteria, out of 18 patients to meet its primary endpoint.

About Tipifarnib

Kura Oncology’s lead candidate, tipifarnib, is an inhibitor of farnesylation, a key cell signaling process implicated in cancer initiation and development. In extensive clinical trials, tipifarnib has shown a well-established safety profile and compelling and durable anti-cancer activity in certain patient subsets. Preclinical and clinical data suggest that, in the appropriate context, tipifarnib has the potential to provide significant benefit to cancer patients with limited treatment options. Leveraging advances in next-generation sequencing as well as emerging information about cancer genetics and tumor biology, Kura Oncology is seeking to identify patients most likely to benefit from tipifarnib. In addition to its development program in solid tumors with HRAS mutations, Kura has identified potential biomarkers of activity for tipifarnib in hematologic malignancies, including peripheral T-cell lymphomas (PTCL), myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML).

On February 15, 2018 Cytokinetics, Incorporated (Nasdaq:CYTK) reported financial results for the fourth quarter of 2017. Net loss for the fourth quarter was $40.5 million, or $0.75 per basic share and diluted share, respectively, compared to net income for the same period in 2016 of $7.2 million, or $0.18 and $0.16 per basic and diluted share, respectively (Press release, Cytokinetics, FEB 15, 2018, View Source [SID1234524001]). Cash, cash equivalents and investments totaled $285.4 million at December 31, 2017.

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"We had a productive fourth quarter and begin the year with optimism for our growing pipeline of muscle biology directed drug candidates," said Robert I. Blum, Cytokinetics’ President and Chief Executive Officer. "In 2018, we are looking forward to results from four mid-stage clinical trials of CK-2127107 in our skeletal muscle activator program which may inform plans to advance to a Phase 3 clinical program under our collaboration with Astellas. Additionally, enrollment in GALACTIC-HF remains on track with planning under our collaboration with Amgen. Our research continues to power innovation with two potential drug candidates expected to move through IND-enabling studies and into Phase 1 trials in 2018."

Recent Highlights and Upcoming Milestones

Cardiac Muscle Program

omecamtiv mecarbil (cardiac myosin activator)

Continued site activation and patient enrollment in GALACTIC-HF, the Phase 3 cardiovascular outcomes clinical trial of omecamtiv mecarbil. Enrollment is proceeding according to plan with patients that have the intended risk profile consistent with the trial design.

Continued protocol development, feasibility assessments, regulatory interactions and other readiness activities for a second Phase 3 clinical trial of omecamtiv mecarbil. This trial which is intended to evaluate the potential of omecamtiv mecarbil to increase exercise performance in patients with heart failure is planned to be conducted by Cytokinetics in collaboration with Amgen.

Announced that a post-hoc responder analysis from COSMIC-HF (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure), a Phase 2 clinical trial evaluating omecamtiv mecarbil in patients with chronic heart failure and left ventricular systolic dysfunction, was presented by John Teerlink, M.D. in an Abstract Rapid Fire Oral presentation at the American Heart Association Scientific Sessions. The proportion of patients achieving various thresholds in the percent reduction of NT-proBNP was larger in patients who received omecamtiv mecarbil than in patients who received placebo.
Skeletal Muscle Program

tirasemtiv (fast skeletal muscle troponin activator (FSTA))

Announced the presentation of results from VITALITY-ALS (Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices after Treatment for a Year in ALS), the international Phase 3 clinical trial of tirasemtiv in patients with amyotrophic lateral sclerosis (ALS), at the 28th International Symposium on ALS and Motor Neurone Disease (MND) in Boston. The presentation, by Jeremy Shefner, M.D., Ph.D., Lead Investigator of VITALITY-ALS, Professor and Chair of Neurology at Barrow Neurological Institute, and Professor and Executive Chair of Neurology at University of Arizona, Phoenix, followed our prior announcement that the trial did not meet the primary endpoint of change from baseline in slow vital capacity which was evaluated at 24 weeks following randomization or any of the secondary endpoints in the trial which were evaluated at 48 weeks.

Continued treatment of patients in VIGOR-ALS (Ventilatory Investigations in Global Open-Label Research in ALS), an open-label clinical trial designed to assess the long-term safety and tolerability of tirasemtiv in patients with ALS who have completed participation in VITALITY-ALS. Currently, there are still over 100 patients who are receiving tirasemtiv in VIGOR-ALS.
CK-2127107, reldesemtiv (next-generation fast skeletal muscle troponin activator)

Received final approval from the World Health Organization and the United States Adopted Name Council for reldesemtiv to be used as the International Nonproprietary Name for CK-2127107.

Continued conduct of our Phase 2 clinical trial of reldesemtiv which is designed to assess its effect on multiple measures of muscle function in both ambulatory and non-ambulatory patients with SMA. This trial has enrolled over 60 patients toward the objective of 72 patients and is being conducted by Cytokinetics in collaboration with Astellas.

Continued site activation and patient enrollment in FORTITUDE-ALS (Functional Outcomes in a Randomized Trial of Investigational Treatment with CK-2127107 to Understand Decline in Endpoints – in ALS), the Phase 2 clinical trial of reldesemtiv which is designed to assess the change from baseline in the percent predicted slow vital capacity (SVC) and other measures of skeletal muscle function after 12 weeks of treatment with reldesemtiv in patients with ALS. This trial has screened over 100 patients and enrolled nearly 90 patients toward the objective of 445 patients and is being conducted by Cytokinetics in collaboration with Astellas.

Continued site activation and patient enrollment in the Phase 2 clinical trial of reldesemtiv in patients with chronic obstructive pulmonary disease (COPD) which is designed to assess its effect on physical function. This trial has enrolled over 30 patients towards the objective of 40 patients and is being conducted by Astellas in collaboration with Cytokinetics.

Continued site activation and patient enrollment in the Phase 1b clinical trial of reldesemtiv in elderly subjects with limited mobility which is designed to assess its effect on measures of physical function. This trial has enrolled over 20 subjects towards the objective of 60 subjects and is being conducted by Astellas in collaboration with Cytokinetics.

Announced the publication of "CK-2127107 Amplifies Skeletal Muscle Response to Nerve Activation in Humans," in Muscle & Nerve, which showed that reldesemtiv increased the force generated by the tibialis anterior muscle versus placebo in response to nerve stimulation in a dose, plasma concentration, and frequency-dependent manner. Single doses of reldesemtiv were well-tolerated in healthy volunteers up to 4000 mg. No serious adverse events were reported and adverse events were all mild or moderate.
Pre-Clinical Research and Development

Advanced a next-generation cardiac muscle activator into development under our collaboration with Amgen. This milestone triggered a $1 million payment from Amgen to Cytokinetics.

Advanced a next-generation skeletal muscle activator into development under our collaboration with Astellas.

Announced that Cytokinetics is advancing an unpartnered cardiac sarcomere directed compound from research into IND-enabling studies in 2018.

Continued collaboration activities under our joint research program with Amgen directed to the discovery of next-generation cardiac muscle activators and under our joint research program with Astellas directed to the discovery of next-generation skeletal muscle activators. Cytokinetics and Astellas recently agreed to extend the joint research program through 2019.

Company scientists continued independent research activities directed to our other muscle biology programs.
Financials

Revenues for the year ended December 31, 2017 included $11.0 million in milestone revenues from Amgen as well as $1.3 million of research and development revenues from our collaboration with Amgen, and $11.9 million of research and development revenues plus $8.8 million of license revenues from our collaboration with Astellas. Revenues for the year ended December 31, 2017 were offset by $20.0 million (out of the total of $40 million) for payments to Amgen related to our option to co-fund the Phase 3 development program of omecamtiv mecarbil in exchange for an increased royalty upon potential commercialization. Revenues in 2016 were primarily due to license revenue from the September 2016 expansion of our collaboration with Astellas and a $26.7 million milestone payment from Amgen.

Research and development expenses for the three months and year ended December 31, 2017 increased to $26.3 million and $90.3 million, respectively, from $18.8 million and $59.9 million for the same periods in 2016, primarily due to increased clinical activity, including activity for VITALITY-ALS, increased clinical trials activity for reldesemtiv, as well as increased personnel.

General and administrative expenses for the three months and year ended December 31, 2017 increased to $10.3 million and $36.5 million, respectively, from $6.7 million and $27.8 million for the same periods in 2016, primarily due to increased personnel, non-cash stock compensation expense and commercial readiness activities.

2018 Financial Guidance

The Company also announced financial guidance for 2018. The company anticipates cash revenue will be in the range of $17 to $23 million, operating expenses will be in the range of $105 to $115 million, and net cash utilization will be approximately $100 million.

2018 Corporate Milestones

Cardiac Muscle Program

omecamtiv mecarbil (cardiac myosin activator)

Expect to complete enrolling patients with chronic heart failure in GALACTIC-HF in approximately one year.

Expect to finalize plans and prepare to start the second Phase 3 trial of omecamtiv mecarbil.
Skeletal Muscle Program

CK-2127107 (reldesemtiv), (next-generation fast skeletal muscle troponin activator (FSTA))

Expect results from a Phase 2 clinical trial of reldesemtiv in patients with SMA in Q2 2018.

Expect results from a Phase 2 clinical trial of reldesemtiv in patients with ALS in 2H 2018.

Expect results from a Phase 2 clinical trial of reldesemtiv in patients with COPD in 2H 2018.

Expect results from a Phase 1b clinical trial of reldesemtiv in adults with limited mobility in 2H 2018.
Pre-Clinical Research

Expect to advance one development compound, under each of our collaborations with Amgen and Astellas, into IND-enabling studies in 2018, one of which may proceed to Phase 1 this year.

Expect to advance an unpartnered cardiac sarcomere directed compound through IND-enabling studies in 2018 to enable initiation of Phase 1 in 2018.
Conference Call and Webcast Information

Members of Cytokinetics’ senior management team will review the company’s fourth quarter results via a webcast and conference call today at 4:30 PM Eastern Time. The webcast can be accessed through the Investors & Media section of the Cytokinetics website at www.cytokinetics.com. The live audio of the conference call can also be accessed by telephone by dialing either (866) 999-CYTK (2985) (United States and Canada) or (706) 679-3078 (international) and typing in the passcode 3665278.

An archived replay of the webcast will be available via Cytokinetics’ website until February 22, 2018. The replay will also be available via telephone by dialing (855) 859-2056 (United States and Canada) or (404) 537-3406 (international) and typing in the passcode 3665278 from February 15, 2018 at 7:30 PM Eastern Time until February 22, 2018.

On February 15, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s New Drug Application (NDA) for ivosidenib (AG-120) for the treatment of patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with an isocitrate dehydrogenase 1 (IDH1) mutation (Press release, Agios Pharmaceuticals, FEB 15, 2018, View Source [SID1234523997]). The NDA was granted Priority Review and has been given a Prescription Drug User Fee Act (PDUFA) action date of August 21, 2018. The FDA’s Priority Review status accelerates the review time from 10 months to a goal of six months from the day of filing acceptance and is given to drugs that may offer major advances in treatment or may provide a treatment where no adequate therapy exists. Agios completed the NDA submission in late December 2017.

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"After decades of little change, treatment of AML has begun to shift dramatically as result of new therapies, and IDHm inhibitors will play an important role in how we treat this terrible disease," said David Schenkein, M.D., chief executive officer of Agios. "Today marks an important milestone in our efforts to rapidly advance what could be the first targeted treatment for R/R AML patients with an IDH1 mutation. We appreciate the FDA’s collaboration during the application process, and we look forward to continuing our productive dialogue."

Ivosidenib is a first-in-class, oral, targeted inhibitor of mutant IDH1. The NDA submission is based on results from AG120-C-001, a Phase 1 dose-escalation and expansion study of ivosidenib in patients with advanced hematologic malignancies and an IDH1 mutation. Data from the R/R AML patients in this study were presented at the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

Additionally, Abbott has submitted a Premarket Approval (PMA) application for the FDA review of an IDH1 assay on the Abbott m2000 RealTime System, an automated sample preparation and batch analyzer system for nucleic acid amplification and detection. In 2014, Abbott and Agios entered into an exclusive agreement under which Abbott is responsible for development and commercialization of a RealTime PCR assay for detection of the IDH1 mutation in bone marrow and blood. The Abbott assay will serve as a companion diagnostic for ivosidenib.

IDH1 mutations occur in about 6 to 10 percent of AML patients. Recent publications have highlighted the advances in the understanding of the genetics underlying AML and the need for routine mutational analysis at diagnosis and relapse.

Ivosidenib is an investigational drug that has not been approved for any use in any country.

About Acute Myelogenous Leukemia (AML)
AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and the median age at diagnosis is 68. The vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 20 to 25 percent. IDH1 mutations are present in about 6 to 10 percent of AML cases.