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.

On December 13, 2017 Iovance Biotherapeutics, Inc. (NASDAQ:IOVA), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported that it is hosting an Analyst Day, Wednesday, December 13, 2017, beginning at 9:00am ET, in New York City (Press release, Iovance Biotherapeutics, DEC 13, 2017, View Source;p=RssLanding&cat=news&id=2322493 [SID1234522621]). During the event, the company will provide an update on its lead program in metastatic melanoma, including a presentation of updated data showing partial responses in four out of 10 patients in cohort 2 in the C-144-01 trial. The company will also review its two additional company-sponsored trials in recurrent, metastatic, or persistent cervical cancer and recurrent or metastatic squamous cell carcinoma of the head and neck as well as an expansion of the TIL pipeline into lung cancer. Additionally, the company’s proprietary Generation 2 (Gen 2) manufacturing process has now been selected for all ongoing and future TIL clinical development.

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"Iovance has made substantial progress in 2017 and we are eager to showcase our work during today’s Analyst Day. We have formally selected Gen 2 as the manufacturing process to be used for registration and have switched all the ongoing study protocols over to this process," said Dr. Maria Fardis, PhD, MBA, president and chief executive officer of Iovance Biotherapeutics. "We are also enthusiastic about our expansion into lung cancer. In collaboration with two industry-leading partners, we will explore the potential of TIL therapy alone and in combination with approved systemic agents. The study at Moffitt has been initiated and the Iovance study, with MedImmune, combining TIL and durvalumab will start in the first half of 2018. We also will provide an update regarding data from cohort 2 of the C-144-01 melanoma study confirming partial responses in four out of 10 patients."

Manufacturing Update

Iovance announced today that it has selected its Gen 2 manufacturing process for all three Phase 2 trials and for all future TIL clinical development. The protocols for the company’s three existing studies have all been amended to allow for enrollment of new patients with TIL manufactured with the Gen 2 process. Cohort 1 of the C-144-01 melanoma study will be closed and new patients will be enrolled in cohort 2. The Gen 2 manufacturing process takes 22 days and the final cell product is cryopreserved for ease of scheduling and handling. The decision to use the Gen 2 manufacturing process was based on data recently presented at the SITC (Free SITC Whitepaper) 2017 Annual Meeting in November, the approximately 35 percent reduction in cost of manufacturing as well as the benefits to patients which include minimizing the time a patient has to wait to receive their TIL and flexibility of scheduling the dosing. Iovance has filed multiple provisional patent applications specific to this process, which if granted, could provide exclusive rights through 2038.

Highlights from Three Lead Clinical Programs

Phase 2 trials are ongoing with adoptive cell transfer (ACT) therapies that utilize an autologous TIL manufacturing process in metastatic melanoma, recurrent, metastatic, or persistent cervical cancer and recurrent and/or metastatic squamous cell carcinoma of the head and neck.

C-144-01 is a Phase 2 multicenter study evaluating the safety and efficacy of LN-144, Iovance’s lead product candidate for treatment of patients with metastatic melanoma. The study is currently enrolling. To date, Iovance has 11 active clinical sites in the United States and intends to start enrolling patients at clinical sites in Europe in early 2018. In November 2017, the company reported results from cohort 2 of the C-144-01 study at the SITC (Free SITC Whitepaper) Annual Meeting. The data being presented today show an objective response rate of 40 percent, with four of ten patients showing a partial response. The most common side effects were pyrexia, anemia and decreased neutrophil count. These patients had a high tumor burden despite a median of 3.6 prior therapies including anti-CTLA and PD-1 treatment.

C-145-03 is a Phase 2, multicenter study that will enroll up to 47 patients and will assess the safety and efficacy of LN-145 for the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. The trial has met the efficacy threshold for the first stage of the Simon’s two stage design and will therefore continue to enroll patients to the full sample size of 47 per protocol. Iovance has amended the protocol so that newly enrolled patients can be treated using TIL produced from the Gen 2 manufacturing process. Iovance anticipates reporting early data from this study in 2018.

C-145-04 is a Phase 2, multicenter, study that will enroll up to 47 patients and will assess the safety and efficacy of LN-145 for the treatment of patients with recurrent, metastatic, or persistent cervical carcinoma. The study is enrolling patients in the Unites States and is expected to start enrollment of patients in Europe in the first half of 2018. Iovance has amended the protocol so that newly enrolled patients can be treated using TIL produced from the Gen 2 manufacturing process.

TIL Pipeline Expansion into Lung Cancer

The company announced today that patient enrollment has begun in a study in collaboration with researchers at H. Lee Moffitt Cancer Center and Research Institute (Moffitt), Stand Up to Cancer, and other collaborators. Patients with advanced non-small cell lung cancer (NSCLC) will be enrolled in a study combining TIL and nivolumab in patients who have progressed on nivolumab.

The company also announced that a Phase 2 study in PD-1 and PD-L1 naïve NSCLC patients, sponsored by Iovance, in collaboration with MedImmune, the global biologics research and development arm of AstraZeneca, will initiate in the first half of 2018. The study with MedImmune will allow for enrollment with LN-145 alone or in combination with durvalumab.

MD Anderson Collaboration Update

Iovance provided an update on its collaboration with the MD Anderson Cancer Center (MDA). Under the collaboration, MDA will initiate two basket studies in sarcoma and platinum resistant ovarian cancer. One study will utilize TIL manufactured by Iovance and for the second study, TIL will be manufactured by MDA. Under the agreement with MDA, Iovance also retains the rights to MDA preclinical research in expanding the understanding of TIL and certain intellectual property related to the MDA TIL manufacturing process.

Today’s Guest Speakers

Key Opinion Leaders will discuss current treatment options and the role of TIL in melanoma, head and neck, lung and cervical cancers. Invited guest speakers include:

Sylvia Lee, MD, University of Washington, Fred Hutch Cancer Research Center
Jason Chesney, MD, PhD, University of Louisville, Brown Cancer Center
Emese Zsiros, MD, PhD, Roswell Park Cancer Institute
Webcast Information
A live webcast of today’s presentation can be accessed on the investor page of Iovance Biotherapeutics’ website at View Source A replay of the webcast will be archived on Iovance Biotherapeutics’ website for 30 days following the presentation.

On December 13, 2017 The Medicines Company (NASDAQ:MDCO) reported that it will host an Investor Day on Tuesday, January 23, 2018, from 10:00 a.m. to 12:30 p.m., Eastern Time, in New York City (Press release, Medicines Company, DEC 13, 2017, View Source [SID1234522626]).

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The event will be led by Fred Eshelman, Pharm.D., Executive Chairman of The Medicines Company, and Clive Meanwell, M.D., Ph.D., Chief Executive Officer of the Company, who will be joined by members of the Company’s management team and outside experts and key members of the ORION coalition, including:

Eugene Braunwald, M.D., Distinguished Hersey Professor of Medicine at Harvard Medical School and founding Chairman of the Thrombolysis in Myocardial Infarction (TIMI) Study Group;
John J.P. Kastelein, M.D., Ph.D., Professor of Medicine and Chairman of the Department of Vascular Medicine at the Academic Medical Center of the University of Amsterdam; and
Marc S. Sabatine M.D., M.P.H., Lewis Dexter, M.D., Distinguished Chair in Cardiovascular Medicine at Brigham and Women’s Hospital, Professor of Medicine at Harvard Medical School and Chairman of the TIMI Study Group.
Presentations and panel discussions will focus on inclisiran, its highly-differentiated value proposition and clinical and non-clinical development, manufacturing, regulatory and pre-commercial projects, as well as on the continuing, unmet medical and market needs in atherosclerotic cardiovascular disease.

The event will be broadcast live via webcast. To access the live webcast and view the accompanying slide presentation, visit the "Investors – Events/Presentations" section of The Medicines Company website at least 15 minutes before the event is scheduled to begin to register and download or install any necessary software. In addition to the webcast, the event can be accessed, in listen-only mode, as follows:

U.S./Canada: (877) 359-9508
International: (224) 357-2393
Conference ID: 60380330
A replay of the webcast will be archived and available after the event for a limited period of time.

The in-person event is reserved for financial analysts and institutional investors and is by invitation 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 [SID1234523072]). 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.

On December 13, 2017 MolMed S.p.A. (MLM.MI) reported that it obtained its first national marketing authorization for its proprietary product, Zalmoxis: the Board of Directors of AIFA (Agenzia Italiana del Farmaco) approved the agreement negotiated between AIFA’s Prices and Reimbursement Committee (CPR) and MolMed, in which the price and reimbursement for Zalmoxis medicinal product were defined (Press release, MolMed, DEC 13, 2017, View Source [SID1234595072]).

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Zalmoxis is MolMed’s first patient specific cell therapy product, based on genetically engineering of the immune system, administered following haploidentical haematopoietic stem-cell transplantation (HSCT) from partially compatible donors to adult patients with leukaemia and other high-risk haematologic malignancies. Zalmoxis is administered from the 21st day post-transplantation and foresees up to a maximum of 4 infusions per patient based on the achievement of immune-reconstitution.

The terms of the agreement provide for an ex-factory price, excluding VAT, of 149,000 EUR per infusion, gross of discounts foreseen by law and of selective reductions foreseen by AIFA Resolutions ("Determinazioni") of 3 July 2006 and 27 September 2006. Furthermore the agreement also set a flat fee per patient and a safeguard clause on sales for the first 24 months. Given the nature of the product, it will be a hospital-only dispensed therapy.

The agreement signed with AIFA will be effective from the fifteenth day subsequent to its publication in the Gazzetta Ufficiale of the Italian Republic.

Riccardo Palmisano, MolMed’s CEO, commented: "This is truly a turning point for a research and development company like MolMed: both Zalmoxis eligibility for reimbursement and the "Aifa granted price" acknowledge the value of our therapy and, at the same time, the successful completion of a top level Italian research, development and manufacturing journey. In addition, this result paves the way to the marketing of this sophisticated genetically engineered cell therapy. This first national authorization allows us to look with increasing confidence to the introduction of Zalmoxis in the other European countries covered by the Dompé agreement, from which we expect relevant results, considering our partner’s value, expertise and successful track record. Zalmoxis commercialization will allow MolMed to increase its revenues from proprietary products on top of those deriving from GMP development and production for third party."

Professor Claudio Bordignon, Founder and Chairman of MolMed, commented: "The inclusion of Zalmoxis among the medicinal products reimbursable by the National Health Service makes this revolutionary therapy available to those patients for whom the allogeneic stem cell transplantation is the best treatment option for high-risk leukaemia and other blood malignancies. In absence of a fully compatible donor, Zalmoxis makes the treatment from a haploidentical family donor safer, by eliminating post-transplant immunosuppression and, at the same time, resolving the potential occurrence of Graft versus Host Disease. Furthermore, Zalmoxis accelerates immune-reconstitution by protecting the patient against infections and leukaemia relapse. Zalmoxis has proven to significantly increase the one-year survival rate in the treated population."

"We are very pleased with the outcome of MolMed’s negotiation with AIFA. By stipulating this agreement, it is stated that Zalmoxis, the first ex-cell cellular therapy based on the immune system engineering for the PRESS RELEASE 2 treatment of adult patients with high risk blood malignancies, responds to a major clinical need", commented Eugenio Aringhieri, Chief Executive Officer of Dompé. "The synergy of our distinctive competences and shared value priorities, on which this alliance with MolMed is founded, will lead us in the interaction with the scientific community and the regulatory authorities aimed at bringing Zalmoxis to all Patients eligible for this therapy."

About Zalmoxis
Zalmoxis is an innovative therapy based on genetically engineering donor immune system T cells to carry an inducible "suicide gene". Administered to patients following HSCT from partially compatible donors (haploidentical HSCT), these cells foster an anti-leukaemia effect by eliminating post-transplant immunosuppression prophylaxis and inducing a rapid immune reconstitution. The suicide gene allows to readily control Graft versus Host Disease (GvHD), the most significant and serious adverse event in haploidentical transplantation, caused by the genetic disparity between patient and donor. Zalmoxis significantly increases long-term survival, regardless of disease status at transplant, thus making HSCT from partially compatible donors safer and more effective. On August 18th, 2016 the European Commission granted a Conditional Marketing Authorisation (CMA) for Zalmoxis, the first immunogene therapy, as patient-specific adjunctive treatment in haplo-identical haematopoietic stem-cell transplantation for adult patients with leukaemia and high-risk haematological malignancies. Following this authorization, which allows MolMed to market Zalmoxis in the 28 EU Member States and in the European Economic Area, activities aimed at its introduction on the European markets have increased. The marketing authorization issued by AIFA is therefore only the first out of the ones on which MolMed has been working since the date of the European CMA.

With the aim of successfully marketing Zalmoxis, on July 26th, 2017 MolMed signed an exclusive license and distribution agreement with Dompé Farmaceutici S.p.A., one of the leading Italian biopharmaceutical companies, granting Dompé the exclusive right and obligation to conduct all activities aimed at promoting, marketing, exploiting, distributing and selling Zalmoxis in all member countries of the current European Economic Area (EEA) and an option right for Switzerland, Turkey and Australia.

In parallel, preparation of the dossier to obtain price and reimbursement of Zalmoxis from the German and French authorities continued through direct interactions. Furthermore activities aimed at starting negotiations with authorities of other countries have been speeded up. In regard to distribution and marketing beyond the European borders, contracts have already been signed with Megapharm Ltd for Israel and with TTY Biopharm Company Ltd for Taiwan and a number of countries in South-East Asia.