Author: [email protected]

Apogenix Granted European Patent for the Use of APG101 in the Treatment of Myelodysplastic Syndromes

On July 19, 2016 Apogenix, a biopharmaceutical company developing next-generation immuno-oncology therapeutics, reported that the European Patent Office has granted the Company a patent for the use of CD95 ligand inhibitors including APG101 in the treatment of myelodysplastic syndromes (MDS) (Press release, Apogenix, JUL 16, 2016, View Source [SID1234524578]). The patent covers the use of such inhibitors in low to intermediate-1 risk transfusion-dependent MDS patients and is valid until July 2033.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

While Apogenix already holds a broad patent portfolio covering APG101, including composition of matter as well as manufacturing and method of treatment of glioblastoma, this is the first patent to cover its clinical use specifically in MDS patients.

"The granting of this additional patent for APG101 further validates our innovative drug development approach and strengthens the protection of our most advanced asset," said Thomas Hoeger, Ph.D., CEO of Apogenix. "With the recently announced positive results from the Phase I trial in MDS patients, we now intend to further develop APG101 in this indication, for which today there are no sufficient treatment options available.

The recently completed Phase I trial evaluated APG101 in low to intermediate-1 risk transfusion-dependent MDS patients and demonstrated the tolerability as well as activity of the drug candidate: APG101 treatment stimulated erythropoiesis and led to a significant decrease in transfusion frequency in this patient population. To further evaluate the efficacy and safety of APG101 in the treatment of MDS patients, Apogenix is currently in preparation of Phase II proof-of-concept trials.
About Myelodysplastic Syndromes (MDS) MDS is a bone marrow disorder that is characterized by ineffective hematopoiesis and can lead to severe anemia. In most cases, the anemia is treated with blood transfusions that eventually result in an iron overload, which can damage the liver and other organs. At the same time, the number of thrombocytesthat are responsible for coagulation and the number of leucocytes that are responsible for immune defense significantly decrease in patients with this disorder. As a result, MDS patients frequently suffer from sudden bleeding and lifethreatening infections. In addition, they are at risk of developing acute myeloid leukemia, a type of blood cancer. About APG101 Apogenix’s lead immuno-oncology candidate APG101 is a fully human fusion protein that consists of the extracellular domain of the CD95 receptor and the Fc domain of an IgG antibody. APG101 is being developed for the treatment of solid tumors and malignant hematological diseases. By blocking the CD95 ligand, which negatively regulates erythrocyte production in MDS patients, APG101 directly addresses the cause of the disorder and could thus potentially provide a cure for MDS.

Sobi publishes its report for the second quarter 2016

On July 15, 2016 (Sobi) reported its results for the second quarter 2016 (Press release, Swedish Orphan Biovitrum, JUL 15, 2016, View Source;Media/News/RSS/?RSS=View Source [SID:1234513892]). Revenue for the quarter totalled SEK 1,469 M (764), an increase of 92 per cent compared to previous year. All parts of the business contributed to the result with Haemophilia, Inflammation and Partner Products delivering strong performance.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Business Summary Q2 2016

Alprolix approved in the EU with first sales reported in Germany in early June
Elocta approved in Switzerland
European patent granted on new formulation of Kineret
Signed licensing agreement with Affibody for IL-1
Signed two manufacturing agreements with Pfizer
Orfadin Oral Suspension and 20 mg capsule approved in the US
Entered into new credit facility and redeemed SEK 800 M bond loan 2012/2017 prior to final maturity
Financial Summary Q2 2016 (Q2 2015)

Total revenue was SEK 1,469 M (764), an increase of 92 per cent (95 per cent at CER)
Product revenue was SEK 1,288 M (593), an increase of >100 per cent (>100 per cent at CER)
Revenues include a SEK 386 M one-time credit from Biogen triggered by first commercial sales of Alprolix
Gross margin was 72 per cent (63)
EBITA was SEK 550 M (74)
Earning per share 0.99 SEK (-0.01)
"The highlight of the first half of 2016 has been the launch of our long-acting Haemophilia franchise in Europe, with supporting achievements seen in the solid growth across the commercial portfolio, and in several milestones including two significant new manufacturing agreements with Pfizer, two Orfadin approvals and the granting of a European patent for a new citrate free formulation of Kineret", said Geoffrey McDonough, CEO and Pesident at Sobi.

"During the quarter, we have continued to build momentum for the launch of Elocta and we now have patients using the product in Germany, UK, Ireland, Sweden and in the Middle East. It has also been an exciting quarter for Alprolix with the approval by the European Commission in May. We are very pleased that Alprolix is now commercially available in Germany, and continue to work to make this innovative treatment available as quickly as possible in more countries in Europe in a similar launch sequence as for Elocta."

Financial Summary
Q2 Q2 H1 H1 Full year
Amounts in SEK M 2016 2015 Change 2016 2015 Change 2015
Total revenues1 1,469 764 92% 2,742 1,629 68% 3,228
Gross profit 1,065 482 >100% 2,009 1,001 >100% 2,007
Gross margin 72% 63% 73% 61% 62%
EBITA 550 74 >100% 1,052 247 >100% 433
EBIT (Operating profit/loss) 453 3 >100% 862 105 >100% 146
Profit/loss for the period 265 -2 >100% 567 73 >100% 68
1 Q2 2016 revenues include a one time credit of SEK 386 M relating to first commercial sales of Alprolix. H1 2016 revenues also include the one time credit received in Q1 of SEK 322 M relating to first commercial sales of Elocta.
Outlook 2016 – unchanged

Sobi continues to expect total revenue for the full year to be in the range of SEK 4,800 to 5,000 M. Revenues include one time credits for Elocta of SEK 322 M and for Alprolix SEK 386 M, which do not impact cash. Gross margin is expected be in the range of 68 to 70 per cent.

Sobi will continue to invest in the launches of Elocta and Alprolix, and will also take on incremental costs of SEK 250 – 300 M reflecting its 50 per cent share of Biogen’s ongoing development costs for the products. Sobi will assume these costs when it becomes marketing authorisation holder for Elocta, which occurred 24 March 2016; and for Alprolix expected in the second half of the year. These incremental costs are included in this outlook.

Sobi expects EBITA for the full year to be in the range of SEK 1,200 to 1,300 M.

ZIOPHARM Issues Statement Regarding Phase I Study of Gene Therapy Candidate Ad-RTS-hIL-12 in Brain Cancer

On July 15, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP) reported the following statement regarding the Company’s ongoing multicenter Phase 1 study of Ad-RTS-hIL-12 + orally administered veledimex in recurrent or progressive glioblastoma (GBM) or grade III malignant glioma:

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This Phase I study is being conducted in late-stage, recurrent GBM, so these patients are all, unfortunately, medically fragile. The first two patient deaths, which occurred 6.7 months and 3.9 months after treatment, were unrelated to study drug (Press release, Ziopharm, JUL 15, 2016, View Source [SID:1234513900]). A third death has just been reported to us and we are collecting and analyzing information in order to properly and timely report it to the FDA. The cause of death is intracranial hemorrhage, which occurred some time after the patient had been discharged from the treating center. This is an isolated case, and there have been no reported related instances of brain hemorrhage in any pervious cohort or prior studies with Ad-RTS-hIL-12 + veledimex. Enrollment remains open in the study, and we will be discussing with our Safety Review Committee the appropriate course of action. For patients who have experienced multiple recurrences, as these patients have, prognoses are particularly poor. Median follow up in the first dose cohort from our study is now 8 months, in a population with an expected overall survival of 3 to 5 months for patients that have failed temozolomide and bevacizumab, or equivalent salvage chemotherapy. For the patients that remain in follow up in this Phase I study, we believe that preliminary overall survival remains encouraging. The Company expects to provide an update once a course of action has been determined."

About Glioblastoma

Glioblastoma is an aggressive primary brain tumor affecting approximately 74,000 people worldwide each year.i, ii Recurrent glioblastoma is an aggressive cancer with one of the lowest 3-year survival rates, at 3%, among all cancers.iii For patients who have experienced multiple recurrences the prognosis is particularly poor, with a median overall survival (OS) of 6-7 months, while OS in patients that have failed temozolomide and bevacizumab, or equivalent salvage chemotherapy, is approximately 3-5 months.iv, v

REVLIMID® (Lenalidomide) Approved by the European Commission for the Treatment of Relapsed/Refractory Patients with Mantle Cell Lymphoma

On July 15, 2016 Celgene International Sàrl, a wholly owned subsidiary of Celgene Corporation (NASDAQ: CELG) reported that the European Commission (EC) has approved REVLIMID (lenalidomide) for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) (Press release, Celgene, JUL 15, 2016, View Source [SID:1234513887]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

MCL is a rare sub-type of aggressive non-Hodgkin’s lymphoma (NHL), which starts in the lymph nodes but can move to other organs, causing tumours known as lymphomas. Between 3 and 6 percent of NHL patients have MCL. MCL has the poorest long-term survival of all B-cell lymphoma subtypes, with fewer than 50 percent of patients surviving at 5 years1. In Europe there were 93,433 new cases of non-Hodgkin lymphoma, and 37,900 deaths in 20122. MCL has a median age of onset of 70 years and affects men more often than women3.

"New treatment options are vitally needed in order to change the course of MCL for patients, given the severity of the disease, and there are still limited existing treatment options," said Prof. Marek Trneny, Charles University in Prague. "Lenalidomide is a proven medicine that has shown efficacy in relapsed/refractory MCL, with the MCL-002 study meeting its primary endpoint of an improvement in progression-free survival (PFS)."

Tuomo Pätsi, President of Celgene in Europe, Middle East and Africa (EMEA), adds: "Today is an important milestone in the fight to find new treatment options for patients with MCL, a difficult-to-treat disease with a high unmet medical need. The approval by the European Commission for REVLIMID in relapsed/refractory MCL gives us the opportunity to support patients in their fight against this disease, with an innovative treatment, and it is only the beginning of our work to support the needs of patients with MCL. We have a robust clinical program of lymphoma studies reaching patients across the globe with an aim to find new treatment options across numerous types of lymphoma."

The EC decision was based on data from MCL-002, a phase II, multicenter, randomized open-label study to determine the efficacy and safety of REVLIMID versus the investigator’s choice (IC), in 254 patients who were refractory to their last treatment or had relapsed one to three times. In the study, REVLIMID showed a significant improvement in progression-free survival (PFS) of 8.7 months vs. 5.2 in the control arm (HR = 0.61, p value of .004)4.

In the study, the most frequently observed adverse reactions which occurred more frequently in the REVLIMID arm compared with the IC arm were neutropenia (50.9%), anaemia (28.7%), diarrhoea (22.8%), fatigue (21.0%), constipation (17.4%), pyrexia (16.8%), and rash (16.2%).

The EC decision for the use of REVLIMID in adult patients with relapsed/refractory MCL follows the positive opinion issued by the Committee for Medicinal Products for Human Use (CHMP) earlier this year. The EC decision marks the 6th new product or indication granted to Celgene in the last 18 months in the European Union. In 2015, Celgene announced the EC approval of medicines for newly diagnosed multiple myeloma, another form of blood cancer; psoriasis and psoriatic arthritis; a specific subset of acute myeloid leukaemia (AML) patients; and non-small-cell lung cancer (NSCLC).

In addition to the EU approval, REVLIMID is indicated for the treatment of patients with relapsed/refractory MCL in the United States, Switzerland, Israel, Turkey, Australia, and numerous countries in Latin America. REVLIMID is also indicated in various countries including the EU for treatment of newly diagnosed and relapsed/refractory multiple myeloma and myelodysplastic syndromes.

IMPORTANT SAFETY INFORMATION

WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity

Do not use REVLIMID during pregnancy. Lenalidomide, a thalidomide analogue, caused limb abnormalities in a developmental monkey study. Thalidomide is a known human teratogen that causes severe life-threatening human birth defects. If lenalidomide is used during pregnancy, it may cause birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting REVLIMID treatment. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after REVLIMID treatment.

Hematologic Toxicity (Neutropenia and Thrombocytopenia)

REVLIMID can cause significant neutropenia and thrombocytopenia. Eighty percent of patients with del 5q MDS had to have a dose delay/reduction during the major study. 34% of patients had to have a second dose delay/reduction. Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled in the study. Patients on therapy for del 5q MDS should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter. Patients may require dose interruption and/or reduction. Patients may require use of blood product support and/or growth factors.

Venous and Arterial Thromboembolism

REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as risk of myocardial infarction and stroke in patients with MM who were treated with REVLIMID and dexamethasone therapy. Monitor for and advise patients about signs and symptoms of thromboembolism. Advise patients to seek immediate medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. Thromboprophylaxis is recommended and the choice of regimen should be based on an assessment of the patient’s underlying risks.

About REVLIMID

REVLIMID is approved in Europe for the treatment of adult patients with previously untreated multiple myeloma (MM) who are not eligible for transplant. REVLIMID is also approved in combination with dexamethasone for the treatment of patients with MM who have received at least one prior therapy in nearly 70 countries, encompassing Europe, the Americas, the Middle-East and Asia, and in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy in Australia and New Zealand.

REVLIMID is also approved in the United States, Canada, Switzerland, Australia, New Zealand and several Latin American countries, as well as Malaysia and Israel, for transfusion-dependent anaemia due to low- or intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities and in Europe for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate.

In addition, REVLIMID is approved in the United States for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. In Switzerland, REVLIMID is indicated for the treatment of patients with relapsed or refractory MCL after prior therapy that included bortezomib and chemotherapy/rituximab.

Panther Biotechnology Announces the Initiation of Formal Development of Transferrin Doxorubicin Conjugate

On July 14, 2016 Panther Biotechnology, Inc. (OTC PINK: PBYA) (Panther), a biotechnology company specializing in the development of enhanced therapeutics for the treatment of neoplastic and autoimmune disorders reported that it has initiated the formal drug development process for its lead compound, Transferrin Doxorubicin (TRF-DOX) (Press release, Panther Biotechnology, JUL 14, 2016, View Source [SID1234517416]). In April 2015, Panther entered into a definitive agreement with privately held Faulk Pharmaceuticals, Inc. to acquire Faulk’s pharmaceutical technology assets which included TRF-DOX. The transaction provided Panther with a proprietary, multi-nationally patent protected, ligand-drug conjugate technology platform as well as a pipeline of drug product candidates that address unmet medical needs in oncology, autoimmune, antiviral and other disease indications. Panther was particularly interested in the TRF-DOX conjugate as it has shown promising safety and preliminary efficacy in a randomized controlled study of ovarian cancer outside the US.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Panther has executed an agreement with Dr. Patricia D. Williams of IND Directions, LLC in Washington DC to lead all aspects of the drug development process for TRF-DOX including regulatory, preclinical, manufacturing and clinical development activities. Dr. Williams has over 30 years of experience designing and implementing high quality drug development programs for small molecules, biologics, and gene therapies. Dr. Williams has held various positions of increasing responsibilities at major pharmaceutical and biotechnology companies (Bristol-Myers, Eli Lilly, American Cyanamid, Ligand, Biochem Pharma) as well as contract research and consulting organizations (SRA Life Sciences, TherImmune, Gene Logic and Summit Drug Development Services). In addition, Dr. Williams has already worked on TRF-DOX with Faulk Pharmaceuticals in the past. Teams under Dr. Williams’ leadership have advanced over 50 small molecules and biologics into clinical development. Under Dr. Williams’ leadership, Panther has initiated the preparation of a formal Pre-Investigational New Drug (IND) submission to the US Food and Drug Administration (FDA). This step will result in FDA’s input into Panther’s Phase II clinical plans with TRF-DOX as well as the preclinical and manufacturing data that will support clinical trials with TRF-DOX.

"We are very excited to work with Dr. Williams to initiate clinical development of the Faulk Pharmaceutical technology, which we see as complementary to our efforts to develop and commercialize innovative pharmaceutical approaches for the treatment of cancer. Not only does Dr. Williams provide enormous experience, her previous work on the TRF-DOX will be invaluable to our efforts," stated Evan Levine, Chief Executive Officer of Panther. "The goal of this next phase is to present a clinical plan to the FDA that has the opportunity to generate a statistical signal over the reference drug and progress Transferrin Doxorubicin towards commercialization. We will continue to inform the public as critical milestones are achieved."

TRF-DOX is a combination of the iron-binding glycoprotein, transferrin, and Doxorubicin resulting in targeted delivery to tumors with the reduction of serious side effects. TRF-DOX leverages the targeting ability of the plasma glycoprotein transferrin to deliver a powerful chemotherapeutic payload to cancerous cells which have elevated levels of transferrin receptors. In vitro assays demonstrate growth inhibition of cancer cells that are resistant to other chemotherapies including Doxorubicin itself. Cytotoxicity studies demonstrate that a doxorubicin dose reduction of ten to one hundred-fold kills all cancer cells in multiple cancer types. In vivo studies demonstrate that TRF-DOX selectively binds tumors, inhibits tumor growth better than unmodified Doxorubicin, and increases survival. This improved therapeutic index suggests that further improvements in efficacy without added toxicity can be achieved.