Bayer receives approval in China for Stivarga® (regorafenib) for the second-line systemic Treatment of liver cancer (for specialized target groups only)

On December 13, 2017 Bayer reported that the Chinese Food and Drug Administration (CFDA) approved Stivarga (regorafenib) tablets for the second-line treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with Nexavar (sorafenib) (Press release, Bayer, DEC 13, 2017, View Source [SID1234522618]). The data from the pivotal Phase III RESORCE study showed that Stivarga (regorafenib) provided a statistically significant and clinically meaningful improvement in overall survival (OS) versus placebo; the median OS was 10.6 vs 7.8 months, (HR 0.62, 95% CI 0.50-0.78; p<0.0001). Exploratory analyses of the RESORCE trial showed that the median time from the start of prior sorafenib treatment to death was 26 months in patients receiving regorafenib versus 19.2 months in those receiving placebo. Regorafenib is the first drug approved for the second-line treatment of patients with HCC in China. The CFDA approval expands Bayer’s leadership in liver cancer with a treatment plan in HCC involving use of Stivarga directly after progression on Nexavar.

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"Following the approval of Stivarga for the treatment of metastatic colorectal cancer and gastrointestinal stromal tumors earlier this year in China, the approval in HCC brings new hope to Chinese patients with HCC who previously had no effective treatment options after being treated with Nexavar", said Robert LaCaze, Member of the Executive Committee of Bayer AG’s Pharmaceuticals Division and Head of the Oncology Strategic Business Unit. "The product is already approved for the treatment of HCC in many countries around the world, including US, Japan and in the EU, and this milestone expands Bayer’s global leadership in liver cancer."

Liver cancer is often more difficult to treat than other cancers with 466,000 new cases diagnosed and 422,000 deaths in China per year. Globally, it is the second leading cause of cancer-related deaths.

About Regorafenib (Stivarga)
Regorafenib is an oral multi-kinase inhibitor that potently blocks multiple protein kinases involved in tumor angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF), metastasis (VEGFR3, PDGFR, FGFR) and tumor immunity (CSF1R).

Regorafenib is approved under the brand name Stivarga in more than 90 countries worldwide, including the U.S., countries of the EU, China and Japan for the treatment of metastatic colorectal cancer (mCRC). The product is also approved in over 80 countries, including the U.S., countries of the EU, China and Japan, for the treatment of metastatic gastrointestinal stromal tumors (GIST). This year, it was also approved in the U.S., Japan and countries of the EU for second-line treatment of HCC.

In the EU, Stivarga is indicated as monotherapy for the treatment of adult patients with mCRC who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and an anti-EGFR therapy, as well as for the treatment of adult patients with unresectable or metastatic GIST who progressed on or are intolerant to prior treatment with imatinib and sunitinib, and for the treatment of adult patients with HCC who have been previously treated with sorafenib.

Regorafenib is a compound developed by Bayer. In 2011, Bayer entered into an agreement with Onyx, now an Amgen subsidiary, under which Onyx receives a royalty on all global net sales of regorafenib in oncology.

About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative cancer treatments. The oncology franchise at Bayer currently includes three oncology products and several other compounds in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways, with the potential to impact the way that cancer is treated.

PRINCIPIA BIOPHARMA INITIATES CLINICAL TRIAL FOR PRN1008 IN PATIENTS WITH IMMUNE THROMBOCYTOPENIA PURPURA

On December 13, 2017 Principia Biopharma, a private, clinical-stage biopharmaceutical company, reported that it has initiated a clinical trial for PRN1008, a reversible covalent Bruton’s Tyrosine Kinase (BTK) inhibitor, in patients with Immune Thrombocytopenia Purpura (ITP) in the US. ITP, an autoimmune disorder characterized by thrombocytopenia – a decreased number of circulating platelets – is the second indication for which Principia is evaluating PRN1008 (Press release, Principia Biopharma, DEC 13, 2017, View Source [SID1234522663]). Principia also has an on-going clinical program for PRN1008 in patients with pemphigus, another autoimmune disease, where it has seen a promising efficacy and safety profile to date.

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Supporting advancement into clinical trials, the company recently presented preclinical data at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in Atlanta (abstract #1052). The results from the studies showed that PRN1008 did not adversely affect platelet aggregation in blood from both healthy volunteers and ITP patients. Additionally, results in an animal model of ITP showed that animals treated with PRN1008 had significantly higher platelet counts than control animals (p<0.05).

"These preclinical results are encouraging and provide strong evidence that PRN1008, an oral, BTK inhibitor, inhibits antibody-mediated thrombocytopenia, supporting its study in ITP patients," said Steve Gourlay, MBBS, Ph.D., chief medical officer of Principia Biopharma. "New treatments and modalities are needed for patients with relapsed ITP that are effective in the majority of patients, with fewer toxicities and easier administration than current treatments. Based on these promising early findings, we have initiated the first human clinical trial of PRN1008 in patients with ITP."

Preclinical study design and results
The effect of PRN1008 on platelet function was evaluated in-vitro in the blood from both normal healthy volunteers and patients with ITP. Results showed that treatment with PRN1008 at therapeutically relevant concentrations had no effect on platelet aggregation in either healthy volunteers or ITP patients, and did not interfere with responses to all other platelet agonists tested. In contrast, ibrutinib, a United States Food and Drug Administration-approved BTK inhibitor, had a significant effect on platelet aggregation in healthy volunteers, consistent with published literature.

Additionally, the pharmacologic effect of PRN1008 was evaluated in an animal model of ITP. Animals given three different doses of PRN1008 were challenged with platelet-targeting antibodies, and blood platelet counts were measured. PRN1008 demonstrated significant dose-dependent prevention of platelet loss at six hours compared with the control animals (p<0.05).

About PRN1008
PRN1008 is an oral, reversible covalent BTK inhibitor (Bruton’s Tyrosine Kinase – a component of B-cell signaling and inflammatory pathways in most white blood cell types other than T-cells and plasma cells). It was designed using Principia’s proprietary Tailored Covalency technology to optimize its safety and efficacy profile, resulting in a prolonged and reversible action at the target site while being rapidly eliminated from the body. This approach limits systemic exposure of PRN1008 and enables rapid clinical reversibility of effects on the immune system.

About Immune Thrombocytopenia Purpura
ITP is a chronic autoimmune disease characterized by a decreased number of circulating platelets, which play a key role in clot formation. The disorder affects approximately 70,000 adults in the United States and over 200,000 in the European Union. The typical age of onset of chronic ITP is 40 to 60 years. Individuals with ITP have a tendency to bleed and easily bruise due to blood leaking from capillaries into the skin and mucous membranes. They also suffer from fatigue, diminished quality of life and the risk of mortality (including intracranial hemorrhage).

Approved therapies in the United States for ITP include corticosteroids, intravenous immunoglobulin (IVIg) and splenectomy (surgical removal of the spleen) to stop platelet depletion, and TPO receptor agonists to increase platelet production. There is no cure for ITP and most patients relapse.

About BTK inhibition in autoimmune disease
Bruton’s Tyrosine Kinase (BTK) is a protein important to the proper function of the immune system. BTK is a key part of the signaling pathway downstream of the B-cell and Fcγ receptors on most types of white blood cells except T-cells and plasma cells. Inhibition of BTK results in the down-regulation of various cellular activities that are activated in autoimmune and inflammatory diseases.

Spectrum Pharmaceuticals Highlights Two Oral Presentations on FOLOTYN® (pralatrexate injection) at the 59th Annual Meeting of the American Society of Hematology (ASH)

On December 13, 2017 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology Company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported two oral presentations of data on FOLOTYN and research progress for the treatment of Peripheral T-Cell Lymphoma (PTCL) at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, Spectrum Pharmaceuticals, DEC 13, 2017, View Source [SID1234522641]).

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Abstract #818: Pralatrexate in Combination with Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Previously Untreated Patients with Peripheral T-Cell Lymphoma (PTCL): A Phase 1 Dose-Escalation Study

In this study presented by Dr. Andrei Shustov from Division of Hematology, University of Washington, a total of 31 patients have been enrolled (19 in Part 1; 12 in Part 2). MTD was not reached and pralatrexate dose of 30 mg/m2 in combination with CHOP was selected for Part 2 of the study as predefined by the protocol. The majority of patients were male, white, with the median age of 57.7 years (range, 18-78) at the time of enrollment. PTCL diagnoses included: anaplastic large cell lymphoma, anaplastic lymphomakinase-negative (ALCL, ALK-, n=5), peripheral T-cell lymphoma, not-otherwise specified (PTCL-NOS, n=18), and angioimmunoblastic T-cell lymphoma (AITL, n=5). Fol-CHOP was generally well tolerated with median RDI of 98%. Grade 3/4 adverse events included anemia (23%), neutropenia (23%), fatigue (13%), and vomiting (13%), as well as febrile neutropenia, nausea, and mucositis each in 10% of the patients. SAEs were observed in 13 patients, treatment related SAEs were anemia, febrile neutropenia, dehydration, mucositis, and nausea. Six patients withdrew from study before the completion of the follow-up, and dose reduction or dose delay occurred in four patients. In the 29 patients evaluable for response, the investigator assessed objective response (OR) and complete response (CR) rates were 90% and 66%, respectively.

Abstract #342: The Role of Upfront Hematopoietic Stem Cell Transplantation (HSCT) in Peripheral T-Cell Lymphoma (PTCL) Patients in Complete Remission (CR) with a Special Focus on Nodal PTCL: Report from the Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment (COMPLETE), a Prospective Multicenter Cohort Study

In this study, presented by Dr. Steven Park from Levine Cancer Institute, a total of 499 PTCL patients were enrolled in COMPLETE over 4 years. Two hundred thirteen patients achieved a CR following frontline therapy and had the required locked records for the analysis with a median follow-up of 2.9 years (Range 1.9-4.0). One hundred forty nine (70%) of these received induction therapy without HSCT consolidation and 64 (30%) underwent either autologous (n = 49) or allogeneic (n = 15) HSCT. This is the first report from the largest prospective PTCL database in the U.S. to date to examine the role of HSCT in PTCL patients who are in first CR. Our data demonstrate potential survival advantages of upfront HSCT in patients with nodal PTCL who achieve CR. However, the results should be interpreted with caution given a relatively short median follow up as well as the non-randomized study design. The role of HSCT among various groups of PTCL patients in first CR should further be evaluated in randomized controlled trials.

"We are honored that two oral presentations and multiple abstracts were presented at the 59th ASH (Free ASH Whitepaper) Meeting," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "FOLOTYN was the first drug approved for the treatment of relapsed or refractory PTCL. PTCL is an aggressive disease with a poor prognosis and we are excited that FOLOTYN has the potential to improve outcome for PTCL patients."

Sanofi presents R&D strategy and innovative pipeline

On December 13, 2017 Sanofi reported that it will host an analyst meeting in Paris to discuss the company’s Research and Development strategy, development pipeline and milestones for 2018 (Press release, Sanofi, 13 13, 2017, View Source [SID1234522640]). The company will highlight the progress it has made against "Sustaining Innovation", a key pillar of its 2020 strategic roadmap, and advancing a differentiated portfolio addressing unmet needs.

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The company’s pipeline spans 71 R&D projects, which includes 37 new molecular entities and novel vaccines. At least 10 pivotal phase 3 studies are expected to start over the next 12 months and will evaluate new treatments for:


chronic obstructive pulmonary disease and eosinophilic esophagitis (dupilumab1);


autosomal dominant polycystic kidney disease (ADPKD), a rare kidney disease (venglustat);


type 2 diabetes (efpeglenatide, a once-weekly GLP-1 agonist);


obesity (a GLP-1/GCG dual agonist);


primary progressive multiple sclerosis (alemtuzumab), and;


first line NSCLC2 (cemiplimab).
Regulatory filings expected in the next 12 months include two investigational cancer drugs (cemiplimab and isatuximab), a novel therapy for type 1 diabetes (sotagliflozin) and a potential treatment for uncontrolled, persistent asthma (dupilumab).

"We have seen significant advancement on our ambition to sustain innovation in R&D, with the development of leading technology platforms and proof of concept demonstrated in multiple high-potential projects in late stage trials. We are confident this portfolio will be the foundation for Sanofi’s future long-term growth," said Olivier Brandicourt, MD, Chief Executive Officer at Sanofi.

1
Partnered products: cemiplimab, dupilumab, anti-IL33 mAb (Regeneron); sotagliflozin (Lexicon); efpeglenatide (Hanmi); fitusiran, patisiran (Alnylam); mavacamten, MYK-491 (Myokardia).
2
Non-Small Cell Lung Cancer

1
As a key pillar of the 2020 Roadmap, the new Sanofi R&D model is based on three key strategic shifts:


From small molecules to biologics;


From mono-targeting to multi-targeting compounds; and


From licensing to proprietary assets.

The company has continuously adapted its R&D model in recent years to deliver greater efficiency and excellence in development, resulting in a major uplift in productivity. Since 2016, consistent with the three key strategic shifts outlined above, Sanofi has placed increasing emphasis on developing proprietary technology platforms, including multi-specific antibodies (bi- & tri-specific), siRNA, trigonal peptides, dual and triple agonists, and PRR-Antibody conjugates. It has also leveraged external expertise in targeted platforms such as mRNA mixtures and Nanobodies.

"We aim to advance multi-targeting therapeutic approaches for core disease pathways that have the potential to attack more than one disease at a time or bring improved risk benefit in the treatment of a single disease," said Elias Zerhouni, MD, Global Head of R&D at Sanofi. "2018 will be an important year as we expect multiple milestones for Sanofi’s late-stage pipeline, made possible through the prioritization principles we have consistently applied to our early-stage research programs."

Building a competitive position in Specialty Care

Immunology

Sanofi is strengthening its specialty care portfolio and has executed launches in its fast-growing immunology franchise. Dupilumab, which we are developing in collaboration with Regeneron, has potential across multiple indications. Phase 3 trials for uncontrolled, persistent asthma recently demonstrated a potentially clinically important profile among biologic treatments. Submission in this important indication is expected before the end of 2017. Clinical development is underway in nasal polyposis, eosinophilic esophagitis, food allergies and in pediatric populations in most of these indications. Additionally, phase 3 development for dupilumab is now planned in chronic obstructive pulmonary disease (COPD). Sanofi, in collaboration with Regeneron, also expects to bring SAR440340, an anti-IL-33 antibody, which has the potential for a broader spectrum of immune modulation, into phase 2 in atopic dermatitis, asthma and COPD in 2018, alone or in combination with dupilumab.

Oncology

Sanofi is committed to re-building its position in oncology and has made major progress in the past two years. This strategy is starting to deliver and we anticipate 14 new proof-of-concept studies to be initiated, four potential proof-of-concept readouts, six phase one starts and three BLA/ MAA submissions in 2018. Cemiplimab is an investigational PD-1 checkpoint inhibitor and the

2
backbone of our checkpoint immuno-oncology strategy with our partner Regeneron. It is being studied in cutaneous squamous cell carcinoma (CSCC), for which it was granted "Breakthrough Therapy" designation by the U.S. Food and Drug Administration (FDA). Topline results show high and durable response rates (overall response rate 46.3%) in a pivotal Phase 2 study in 82 patients with advanced CSCC. This positive data has resulted in the initiation of a rolling BLA submission, with completed submission expected in Q1 2018. The development program also includes large or untapped opportunities in immuno-oncology, such as basal cell carcinoma, cervical cancer, and first line lung cancer.
Isatuximab is a Sanofi investigational antiCD38 monoclonal antibody with a first regulatory submission expected in 2018 for relapsed refractory multiple myeloma (RRMM). Beyond multiple myeloma, and building on the emerging evidence that CD38 inhibition may reverse resistance to PD-L1, isatuximab will be studied in combination with cemiplimab or other immuno-oncology agents. Sanofi will also present early research programs for its Selective Estrogen Receptor Degrader (SERD) and TGF-beta program to overcome PD-1 resistance.

Multiple Sclerosis

In multiple sclerosis (MS), Sanofi plans to build on the proven long-term clinical profile of Lemtrada (alemtuzumab) by initiating a Phase 3 study in 2018 for alemtuzumab in patients with primary progressive multiple sclerosis (PPMS). Consistent with Sanofi’s rigorous prioritization methodology, the company will deprioritize GLD-52 in this indication in favor of alemtuzumab. In addition, Sanofi, in collaboration with Principia, will be developing a novel Bruton’s tyrosine kinase (BTK) inhibitor, designed to access the brain and spinal cord by crossing the blood-brain barrier and impact immune cell and brain cell signaling. It is currently being studied in MS with potential applications in other central nervous system diseases3.
Sustaining leadership in Rare Disease, Diabetes & Cardiovascular and Vaccines

Rare Disease
Sanofi’s Rare Disease pipeline is structured with the goal of sustaining innovation in lysosomal storage disorders, while also expanding strategically into related conditions. Clinical development programs include venglustat, an oral inhibitor of glucosylceramide synthase, in Fabry Disease, Gaucher Disease Type 3, GBA Parkinson’s Disease and autosomal dominant polycystic kidney disease (ADKPD). Late-stage/pivotal programs include olipudase, a first-in-class enzyme replacement therapy (ERT) for the non-neurological manifestations of acid sphingomyelinase deficiency (ASMD), and avalglucosidase alfa, a novel ERT for Pompe disease. Finally, through a strategic collaboration with Alnylam, we are advancing the development of patisiran for hATTR4 amyloidosis and fitusiran for hemophilia A and B, with and without inhibitors.

3
The Principia transaction remains subject to customary regulatory approvals and has not yet closed.
4
hATTR = Hereditary Transthyretin-Mediated Amyloidosis

Diabetes & Cardiovascular
Sanofi is committed to sustaining a leadership position in diabetes and expanding into adjacent co-morbidities. Its late-stage diabetes pipeline includes sotagliflozin, an investigational SGLT-1/2 inhibitor being developed in collaboration with Lexicon, and efpeglenatide, a once-weekly GLP-1 being developed in collaboration with Hanmi, both of which potentially offer unique patient advantages. Additionally, Sanofi is leveraging its novel peptide incretin platform to develop breakthrough assets for diabetes, obesity and non-alcoholic steatohepatitis (NASH). The lead compound is a dual agonist of GLP-1/GCG which has shown highly competitive weight loss in the clinic and is expected to enter phase 3 in obesity in 2018. A phase 2 study in NASH is also due to start in 2018.

In cardiovascular, Sanofi continues to work in collaboration with Myokardia on therapeutic options for genetic forms of cardiomyopathy. The lead compound is mavacamten, an oral modulator of cardiac myosin, which is in phase 2 for HCM5 and is expected to start a registrational phase 2b/3 study in 2018.

Vaccines
Sanofi has six key vaccine projects currently in development, and priority disease areas include influenza, meningitis and respiratory syncytial virus (RSV). RSV is the leading cause of infant viral mortality and represents a new potential category for Sanofi. The company is taking a complementary dual approach to RSV with a monoclonal antibody in phase 2, in collaboration with MedImmune, and a vaccine in phase 1.

Webcast details
The event will be webcast live on Sanofi’s website at 8:30 am CET/2:30 am EST. The webcast details and full presentation will be made available on Sanofi’s Investor Relations webpage and an Appendix compiling all Sanofi studies registered on clinicaltrials.gov will also be published.

Iovance Biotherapeutics, Inc., Analyst Presentation-December 2017

On December 13, 2017 Iovance Biotherapeutics, Inc. presented , Analyst Presentation-December 2017 (Presentation, Iovance Biotherapeutics, DEC 13, 2017, View Source [SID1234522633]).

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