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.

Cascadian Therapeutics Added to the Nasdaq Biotechnology Index

On December 13, 2017 Cascadian Therapeutics, Inc. (Nasdaq:CASC), a clinical-stage biopharmaceutical company, reported that it has been selected for addition to the Nasdaq Biotechnology Index (Nasdaq:NBI), which will become effective prior to U.S. market open on Monday, December 18, 2017 (Press release, Cascadian Therapeutics, DEC 13, 2017, View Source [SID1234522627]).

The Nasdaq Biotechnology Index is designed to track the performance of a set of securities listed on the Nasdaq Stock Market (Nasdaq) that are classified as either biotechnology or pharmaceutical according to the Industry Classification Benchmark (ICB). The Nasdaq Biotechnology Index is re-ranked annually and all securities in the index are listed on the Nasdaq Global Market or the Nasdaq Global Select Market, and meet minimum market value and share volume requirements among other criteria. For more information about the Nasdaq Biotechnology Index, including eligibility criteria, visit www.nasdaq.com.

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."

MabVax Therapeutics Announces Completion of Enrollment and Dosing in Initial Cohort of MVT-1075 Radioimmunotherapy Phase 1 Trial for the Treatment of Pancreatic, Colon and Lung Cancers

On December 13, 2017 MabVax Therapeutics Holdings, Inc. (Nasdaq: MBVX), a clinical-stage biotechnology company focused on the development of antibody-based products to address unmet medical needs in the treatment of cancer, reported the completion of enrollment and dosing of all patients in the initial cohort of the Phase 1 clinical trial evaluating the Company’s new human antibody-based radioimmunotherapy ("RIT") product MVT-1075 for the treatment of pancreatic, colon and lung cancer (Press release, MabVax, DEC 13, 2017, View Source [SID1234522631]).

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This Phase 1 first-in-human clinical trial is an open-label, multi-center study evaluating the safety and efficacy of MVT-1075 in approximately 22 patients with CA19-9 positive malignancies in the U.S. The primary objective is to determine the maximum tolerated dose and safety profile in patients with recurring disease who have failed prior therapies. Secondary endpoints are to evaluate tumor response rate and duration of response by RECIST 1.1, and to determine dosimetry and pharmacokinetics. This dose-escalation study utilizes a traditional 3+3 design. The investigative sites include Honor Health in Scottsdale, Arizona and Memorial Sloan Kettering Cancer Center in New York City. The Company plans to report interim results from this study early in the first quarter of 2018 and continue the dose escalation phase of the program.

In April, the Company reported preclinical results for MVT-1075 at the American Association of Clinical Research (AACR) (Free AACR Whitepaper) Annual Meeting, demonstrating marked suppression, and in some instances, regression of tumor growth in xenograft animal models of pancreatic cancer, potentially making this product an important new therapeutic agent in the treatment of pancreatic, colon and lung cancers. Supporting the MVT-1075 RIT clinical investigation are the Company’s successful Phase 1a safety and target specificity data which were reported earlier this year at the annual meetings of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the Society for Nuclear Medicine and Molecular Imaging (SNMMI), including the clinical results for the Company’s MVT-5873 single agent therapeutic antibody and MVT-2163, an immuno-PET imaging agent. The combined results from 50 patients in the Phase 1a MVT-5873 and MVT-2163 studies, established safety and provided significant insight into drug biodistribution and an optimal dosing strategy, which the Company has incorporated into the MVT-1075 program.

MVT-1075 combines the clinically demonstrated tumor targeting characteristics of the Company’s fully human HuMab-5B1 antibody and the commercially validated radionuclide, 177Lutetium, for the purpose of delivering a lethal dose of radiation to the targeted cancer cells.

For additional information about the Phase 1 MVT-1075 clinical trial, please visit clinicaltrials.gov, and reference Identifier NCT03118349.

About MVT-1075

MVT-1075 is a radioimmunotherapy product that combines established efficacy of radiation therapy with tumor specific targeting. It has the potential to deliver a more potent HuMab-5B1 based product. MVT-1075 uses small doses of the Company’s MVT-5873 antibody, coupled to a radioisotope to target pancreatic cancer cells and kill them.

Bristol-Myers Squibb Granted Exclusive License by Ono Pharmaceutical for Multiple Programs Targeting Immuno-Suppressive Factors in the Tumor Microenvironment

On December 13, 2017 Bristol-Myers Squibb Company (NYSE:BMY) and Ono Pharmaceutical Co., Ltd. (Osaka, Japan; President, Representative Director, Gyo Sagara; "Ono") reported an agreement that grants Bristol-Myers Squibb an exclusive license for the development and commercialization of ONO-4578, Ono’s selective Prostaglandin E2 (PGE2) receptor 4 (EP4) antagonist (Press release, Bristol-Myers Squibb, DEC 13, 2017, View Source [SID1234522637]). The companies will also collaborate on discovery efforts to identify additional compounds from Ono’s PGE2 receptor antagonist programs.

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"To improve long-term outcomes for more patients with cancer, we believe more Immuno-Oncology based combinations may be required, and we are pleased to continue our long-standing collaboration with Ono with this focus in mind," said Fouad Namouni, M.D., head of Development, Oncology, Bristol-Myers Squibb. "Ono’s Prostaglandin E2 receptor antagonist programs offer the potential to develop targeted therapies that counteract the effects of an immunosuppressive tumor microenvironment. Researching Prostaglandin E2 receptor antagonists in combination with our oncology portfolio has the potential to result in an enhanced response in a broad range of tumors."

"We are very pleased to collaborate with Bristol-Myers Squibb on ONO-4578, an innovative Immuno-Oncology therapy candidate derived from our long-standing Prostaglandin projects, and to further work with Bristol-Myers Squibb on other Prostaglandin E2 receptor antagonist programs," said Hiroshi Awata, Vice President Executive Officer and Executive Director, Clinical Development, Ono Pharmaceutical Co., Ltd. "We are committed to further pursuing the worldwide development of ONO-4578 with Bristol-Myers Squibb with the goal of improving outcomes of patients suffering from cancer around the world as promptly as possible."

Under the terms of the agreement, Bristol-Myers Squibb will make an upfront payment of $40 million to Ono. Bristol-Myers Squibb will be solely responsible for the development, manufacturing and commercialization of ONO-4578 as well as other PGE2 receptor antagonist products in all countries of the world except Japan, South Korea, Taiwan, China and Association of Southeast Asian Nations (ASEAN) countries. Ono is eligible to receive subsequent clinical, regulatory and sales-based milestone payments, as well as royalties in these countries where Bristol-Myers Squibb has exclusive license. In Japan, South Korea and Taiwan, Bristol-Myers Squibb and Ono will partner on the development and commercialization under the companies’ existing collaboration agreement, while in China and ASEAN countries, Ono will retain exclusive rights.

About Prostaglandin E 2 and Immuno-Oncology

Prostaglandin E2 (PGE2), a major immunosuppressive factor in the tumor microenvironment, is believed to suppress tumor immunity and promote tumor progression. Preclinical data suggests that modulation of PGE2 through any PGE2 receptor antagonists may complement Immuno-Oncology therapies, including anti-PD-1 and anti-CTLA-4, and potentially increase both the rate and durability of response in tumors that are refractory to immunotherapy. Certain patients and tumor types have higher expression of PGE2-related molecules and/or immune characteristics that are more likely to respond to PGE2 receptor blockade, presenting an opportunity for patient stratification to improve outcomes.

About ONO-4578

ONO-4578 is a selective, oral antagonist of EP4, which is a Prostaglandin E2 receptor. In results from experiments using mouse models, ONO-4578 showed an anti-tumor effect by improving immunosuppressive tumor microenvironment. Ono has already commenced Phase I clinical study of ONO-4578 in Japan.

About the Bristol-Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol-Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.