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Encouraging initial results for IPH4102 presented at the Third World Congress of Cutaneous Lymphomas

On October 26, 2016 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH), reported encouraging preliminary safety and clinical activity results from the dose-escalation part of the Phase I study testing IPH4102 in patients with relapsed/refractory cutaneous T-cell lymphomas ("CTCL"), an orphan disease (Press release, Innate Pharma, OCT 26, 2016, View Source [SID1234516012]). IPH4102 is Innate Pharma’s wholly-owned, first-in-class anti-KIR3DL2 humanized therapeutic antibody, designed to trigger immune cell-mediated killing of CTCL cancer cells.

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These data are presented in a poster at the Third World Congress of Cutaneous Lymphomas (October 26-28, 2016, New-York, USA) and will be discussed by the Principal Investigator, Professor Martine Bagot, Head of the Department of Dermatology at Saint-Louis Hospital (Paris) in the Scientific Session "Endpoints & Clinical Trials" on October 28, 2016, 1:30 – 2:45 p.m. EST.

The Phase I study is currently ongoing. Data are reported for the first seven dose levels (0.0001 to 1.5 mg/kg, 16 patients) of the dose-escalation part. In this population, IPH4102 was well-tolerated with no dose-limiting toxicity reported. The majority of adverse events is typical for CTCL or reflects low grade infusion-related reactions. As of September 10, 2016, the best global response rate was 38% across all dosage levels. Complete responses appeared with increasing doses and/or duration of exposure in skin and blood (respectively 2 and 3, seen in 4 patients)[1]. All responses are ongoing at the time of the analysis, which occurred after a median duration of treatment of 126+ days (range of 41+ to 298+).

Three additional dose levels (3, 6 and 10 mg/kg) remain to be evaluated and the dose escalation part of the trial is now expected to be completed by Q2 2017 (previously expected at the end of 2017).

"These preliminary results are very encouraging and fully support the continuation of the development of the antibody candidate. By targeting KIR3DL2 on CTCL cells and triggering their killing by immune effector cells, IPH4102 has the potential to deliver a new treatment option for patients in high medical need at advanced stages of the disease," said Pierre Dodion, Chief Medical Officer of Innate Pharma. "The development of IPH4102 benefits from long lasting collaborations with Saint Louis Hospital in Paris and reference centers, such as Stanford (US). Together we look forward to the complete safety data of the dose-escalation part of the trial and commencing cohort expansion of this new drug candidate, which is wholly-owned by Innate Pharma."

Martine Bagot, Principal Investigator and Head of the Dermatology Department at the Saint-Louis Hospital, Paris, added: "This study offers preliminary safety and efficacy results that are promising for IPH4102, in patients with CTCL subtypes that historically have been shown to be particularly difficult to treat. We are delighted with the progress that has been made with this candidate through translational research and an exceptional academic-industrial partnership."

The study started enrolling patients in November 2015. So far, 16 patients with KIR3DL2-positive CTCL have been enrolled in seven dose-cohorts, including 13 patients with Sézary syndrome, 2 patients with mycosis fungoides and 1 patient with CD4+ CTCL. Median age was 71 years and patients had received 2 to 8 lines of prior systemic therapy for their disease.

All of the 16 patients treated with IPH4102 were evaluable for safety and clinical activity assessments.

As of September 10, 2016, patients had received up to 18 administrations of IPH4102. Treatment is ongoing in 12 patients. Preliminary results of exploratory endpoints such as pharmacodynamics in skin and blood are in line with clinical activity results (see poster #O-11), and show depletion of KIR3DL2-expressing tumor cells in skin and blood of patients after IPH4102 administrations.

Presentation/ Poster Details

The oral presentation, entitled "First-in-Human, open label, multicenter phase I study of IPH4102, first-in-class humanized anti-KIR3DL2 mAb, in relapsed/refractory CTCL: preliminary safety and clinical activity results" will take place on October 28, 2016, 1:30 – 2:45 p.m. EST. It will be available on the Company’s website, in the Product Pipeline – IPH4102 section following the session. The associated poster is displayed during the entire congress and is available on Innate Pharma’s website.

Simultaneously, poster #O-11 entitled "First-in-Human, open label, multicenter phase I study of IPH4102, first-in-class humanized anti-KIR3DL2 mAb, in relapsed/refractory CTCL: preliminary results of exploratory biomarkers" has been presented by Hélène Sicard, Anne Marie-Cardine and Maxime Battistella and is available on Innate Pharma’s website under Product Pipeline – IPH4102.

ARIAD Announces Publication of the Preclinical Profile of Brigatinib in the Journal Clinical Cancer Research

On October 26, 2016 ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) reported the publication of preclinical data on brigatinib, its investigational oral tyrosine kinase inhibitor in development for the treatment of patients with anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer (NSCLC) (Press release, Ariad, OCT 26, 2016, View Source [SID1234516007]). The design and preclinical characterization of brigatinib are described in an article titled, "The Potent ALK Inhibitor Brigatinib (AP26113) Overcomes Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in Preclinical Models," in the journal Clinical Cancer Research (Zhang, S.; et al. Clin Cancer Res. 2016, DOI: 10.1158/1078-0432.CCR-16-0569 Published 25 October 2016).

Activating gene rearrangements in ALK account for approximately three to seven percent of NSCLCs. Disease progression in patients treated with the first-generation ALK inhibitor crizotinib can be associated with secondary resistance mutations in ALK, or the development of brain metastases. Resistance mutations in ALK, including G1202R, have also been associated with disease progression in patients treated with the second-generation ALK inhibitors ceritinib and alectinib. In the preclinical studies described in the paper, brigatinib was shown to be a highly potent and selective inhibitor of ALK, inhibiting ALK at lower concentrations than crizotinib, ceritinib, and alectinib. Furthermore, in these studies, brigatinib was the only inhibitor that showed activity against all 17 tested ALK mutants that have been associated with preclinical or clinical resistance to existing ALK inhibitors, including G1202R. In addition, compared to crizotinib, brigatinib was shown to significantly prolong survival of mice with ALK+ tumors in the brain.

"We believe that these preclinical findings support a molecular basis for the promising systemic and intracranial activity in ALK+, crizotinib-resistant NSCLC patients being treated with brigatinib in clinical trials and further validate our ongoing clinical research to understand the potential of brigatinib to address mutations associated with disease progression," said Victor M. Rivera, Ph.D., vice president of preclinical & translational research at ARIAD. "In addition, we believe that these findings support testing brigatinib as initial therapy in ALK+ NSCLC patients, to see if the greater in vitro potency of brigatinib also manifests in human trials as deeper and more durable responses compared to crizotinib, and whether emergence of ALK resistance mutations can be delayed or even circumvented."

ARIAD has commenced the Phase 3 ALTA 1L clinical trial to compare brigatinib and crizotinib in ALK+ NSCLC patients who have not received prior ALK inhibitors.

Brigatinib Medicinal Chemistry Publication

In addition, the medicinal chemistry strategy leading to the discovery of brigatinib was published in an article titled, "Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase," in the Journal of Medicinal Chemistry, (Huang, W.-S.; et al. J. Med. Chem. 2016, 59, DOI: 10.1021/acs.jmedchem.6b00306).

"This publication details, for the first time, specific design elements that ARIAD scientists utilized in synthesizing brigatinib. Brigatinib features an innovative phosphine oxide recognition motif that is designed to enhance potency and selectivity while also conferring favorable pharmacologic properties," said William C. Shakespeare, Ph.D., vice president of drug discovery at ARIAD. "Brigatinib is the only phosphine oxide-containing molecule to have advanced to late stage clinical trials, showcasing how our innovative chemistry platform can deliver novel drug candidates designed to tackle challenging clinical problems."

About Non-Small Cell Lung Cancer and ALK

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85 percent of the estimated 228,190 new cases of lung cancer diagnosed each year in the United States, according to the American Cancer Society. Anaplastic lymphoma kinase (ALK) was first identified as a chromosomal rearrangement in anaplastic large-cell lymphoma (ALCL). Genetic studies indicate that chromosomal rearrangements in ALK are key drivers in a subset of NSCLC patients as well. Since ALK is generally not expressed in normal adult tissues, we believe that it represents a promising molecular target for cancer therapy. Approximately three to eight percent of patients with NSCLC have a rearrangement in the ALK gene.

About Brigatinib

Brigatinib is an investigational, targeted cancer medicine discovered internally at ARIAD Pharmaceuticals, Inc. It is in development for the treatment of patients with anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) whose disease is resistant or intolerant to crizotinib. Brigatinib is currently being evaluated in the global Phase 2 ALTA trial that is the basis for its initial regulatory review. ARIAD has also initiated the Phase 3 ALTA 1L trial to assess the efficacy and safety of brigatinib in comparison to crizotinib in patients with locally advanced or metastatic ALK+ NSCLC who have not received prior treatment with an ALK inhibitor. More information on brigatinib clinical trials, including the expanded access program (EAP) for ALK+ NSCLC can be found here.

Lynparza Phase III SOLO-2 trial shows significant progression-free survival benefit

On October 26, 2016 AstraZeneca reported positive results from the Phase III SOLO-2 trial designed to determine the efficacy of Lynparza (olaparib) tablets (300mg twice daily) as a monotherapy for the maintenance treatment of platinum-sensitive relapsed, BRCA-mutated ovarian cancer (Press release, AstraZeneca, OCT 26, 2016, View Source [SID1234516002]). Results from the trial demonstrate a clinically-meaningful and statistically-significant improvement of progression-free survival (PFS) among patients treated with Lynparza compared to placebo and provide additional evidence to support the potential use of Lynparza in this patient population.

Importantly, the median PFS in the Lynparza arm of SOLO-2 substantially exceeded that observed in the Phase II maintenance study in patients with platinum-sensitive relapsed ovarian cancer (Study 19).1

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "We are pleased with the robust improvement in progression-free survival demonstrated by Lynparza in the SOLO-2 trial. We will work with regulatory authorities to make Lynparza tablets available as quickly as possible to patients with ovarian cancer. We remain committed to investigating the full potential of Lynparza, both as monotherapy and in combinations, and to identifying all patients who may benefit from this important medicine."

Initial findings demonstrate that safety profile with Lynparza tablets was consistent with previous studies. Full results of SOLO-2 will be presented at a forthcoming medical meeting.

Today’s positive results follow the Fast Track Designation for Lynparza by the US FDA earlier this year, in patients with a BRCA mutation who have platinum-sensitive, relapsed ovarian cancer.

NOTES TO EDITORS

About SOLO-2

SOLO-2 was a Phase III, multicentre trial designed to determine the efficacy of Lynparza tablets as a maintenance monotherapy compared with placebo, in patients with platinum-sensitive relapsed or recurrent BRCA-mutated (BRCAm) ovarian cancer. In SOLO-2, patients with either germline or somatic BRCAm status were eligible for enrolment, although due to the lack of widespread availability of tumour BRCA testing, most patients were enrolled on blood-based germline testing. Those few patients who were enrolled based on a tumour test were also found to have a germline BRCA mutation. Patients were randomised to receive either Lynparza tablets (300mg twice daily) or placebo until disease progression.1

The trial, conducted in collaboration with the European Network for Gynaecological Oncological Trial Groups (ENGOT) and Groupe d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et du sein (GINECO), randomised 295 patients with documented germline BRCA1 or BRCA2 mutations who had received at least 2 prior lines of platinum-based chemotherapy.

About AstraZeneca in ovarian cancer

Worldwide, ovarian cancer is the 7th most commonly diagnosed cancer2 and the 8th most common cause of cancer death in women.3 The risk of developing ovarian cancer is increased in women with specific inherited genetic abnormalities, including BRCA mutations. AstraZeneca is committed to the continued development of our R&D portfolio for ovarian cancer, with a focus on improved care for all patients, including the development of targeted therapies for patients with specific gene mutations such as BRCA.

About Lynparza

Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumour DNA damage response (DDR) pathway deficiencies to preferentially kill cancer cells. It is approved by regulatory authorities in the EU and US for the treatment of women with BRCAm ovarian cancer. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DNA damage response (DDR) mechanisms in cancer cells.

Ipsen reports 12.2% sales growth for the third quarter of 2016 and raises full year guidance

On October 26, 2016 Ipsen (Euronext: IPN; ADR: IPSEY), a global specialty-driven pharmaceutical group, reported its sales for the third quarter and first nine months of 2016 (Press release, Ipsen, OCT 26, 2016, View Source [SID1234516015]).

Commenting on the third quarter 2016 performance, David Meek, Chief Executive Officer of Ipsen said: "We are satisfied with the excellent performance achieved in the third quarter. The momentum of the Specialty Care business accelerated in the third quarter, led by the strong global performance of Somatuline as well as a strong performance of Dysport in the US and Decapeptyl in Europe. The Primary Care business is still experiencing challenges in emerging markets and in the third quarter was particularly adversely impacted by a difficult market environment in Russia and Algeria and a slower ramp-up of the new commercial strategy in China."

David Meek added: "We advanced several pipeline programs during the quarter, most notably for our oncology portfolio the Cabometyx program. The recent approval for the second line treatment of advanced Renal Cell Carcinoma (RCC) in Europe and positive clinical results from the CABOSUN study in first line advanced RCC reinforce our conviction in the potential of Cabometyx. We are fully committed to the launch of Cabometyx in the first European countries in the coming weeks."

Third quarter 2016 sales highlights

Note: Unless stated otherwise, all variations in sales are stated excluding foreign exchange impacts.

Consolidated Group sales grew 12.2% to €390.6 million.

Sales of Specialty Care products reached €319.7 million, up 17.8% year-on-year. The relative weight of Specialty Care continued to increase to reach 81.8% of Group sales, compared to 77.8% the previous year.

Somatuline sales reached €137.0 million, up 34.1%, year-on-year, driven by the continued strong growth in the United States, and by a good overall performance in Europe, notably in Germany, France, and the UK.
Decapeptyl sales reached €84.2 million, up 6.3% year-on-year, supported by strong volume growth in Europe.
Dysport sales reached €73.9 million, up 9.3% year-on-year, led by a solid performance in the United States, notably in aesthetics through the Galderma partnership. This good performance was negatively impacted by volume declines in Brazil due to importation issues and in Russia due to lower demand.
Primary Care product sales totaled €70.9 million, down 7.5% year-on-year, affected by the decline in sales of Tanakan in Russia, Forlax in Algeria, and also the tail portfolio in France.

Smecta sales reached €25.3 million, down 1.0% year-on-year, affected by the sales decrease in China with a slower ramp-up of the new commercial strategy in China, as well as in France and in Italy despite good performance in Russia.
Forlax sales amounted to €9.0 million, down 8.8% year-on-year, affected by the sales decline in Algeria where import programs have been suspended and despite good volume growth in France.
Tanakan sales comprised €8.9 million, down 31.0% year-on-year, impacted by continued market challenges in Russia.

2016 objectives revised

Based on the performance of the first nine months of 2016, the Group raises its guidance for Specialty Care sales to greater or equal to 15% growth and revises its guidance for Primary Care sales to a range of -3% to -5%. The guidance for Core Operating margin is raised to around 22%.

Results Announcement for the third quarter 2016

On October 26, 2016 GSK reported further sales growth, improved cash flow and sustained pipeline progression in Q3 (Press release, GlaxoSmithKline, OCT 26, 2016, View Source [SID1234516014]).

Summary

For GlaxoSmithKline’s full Q3 results announcement, visit: View Source to view full Q3 results announcement (PDF)

Group sales £7.5 billion, +8% CER, with continued growth across all three businesses

New product sales £1.21 billion +79% (Q1 2016: £821 million; Q2 2016: £1.05 billion) driven by HIV (Tivicay, Triumeq), Respiratory (Relvar/Breo, Anoro, Incruse, Nucala) and Meningitis vaccines (Bexsero, Menveo)

Improved operating leverage driven by sales growth, delivery of restructuring and integration benefits and continued tight control of costs including targeted reinvestments

Q3 total earnings per share 16.6p, -1% CER, impacted by charges resulting from increases in valuations of Consumer Healthcare and HIV businesses

Q3 core earnings per share 32p, +12% CER

Continue to expect 2016 core EPS percentage growth to be 11-12% CER

Q3 net cash inflow from operations of £1.8 billion (Q3 2015: £0.5 billion)

19p dividend declared for Q3. Continue to expect 80p for FY 2016 and 2017

Sustained delivery in R&D pipeline