On March 19, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) reported its financial results for the fourth quarter and year ended December 31, 2018 as well as provided corporate and operational updates on clinical trials, research and development, recent hires, and intellectual property (Press release, Actinium Pharmaceuticals, MAR 19, 2019, View Source [SID1234534474]).

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Company Highlights:

Presented interim Phase 3 SIERRA trial data at the 2018 ASH (Free ASH Whitepaper) and 2019 TCT Meetings. The SIERRA trial (Study of Iomab-B in Elderly Relapsed or Refractory AML) is a 150-patient pivotal Phase 3 multi-center randomized trial that will compare outcomes of patients who receive Iomab-B and a BMT or Bone Marrow Transplant to those patients receiving physician’s choice of salvage chemotherapy, defined as conventional care, as no standard of care exists for this patient population. Key highlights from the SIERRA Trial presented at ASH (Free ASH Whitepaper) and the TCT Meetings include:
All patients receiving a therapeutic dose of Iomab-B engrafted despite active disease with high blast count (median 30%, or median 45% for crossover patients)
15 of 19 (79%) patients in the control arm failed to achieve a complete response
67% (10/15) of patients eligible for crossover successfully transplanted after Iomab-B treatment
All patients receiving Iomab-B and a BMT (28/28) achieved Donor Chimerism prior to day 100
94% of patients initially randomized to receive Iomab-B and a BMT (17/18) achieved Full Donor Chimerism > 95% prior to day 100 with 1 patient achieving 65% donor chimerism
90% of patients who crossed-over to receive Iomab-B and a BMT (9/10), after salvage chemotherapy in the control arm failed to produce a CR or Complete Response, also achieved Full Donor Chimerism > 95% prior to day 100 with 1 patient achieving 86% donor chimerism
The SIERRA trial is currently enrolling patients at 18 sites in the U.S and Canada including many of the leading BMT sites based on volume. Patients with active, relapsed or refractory AML have dismal prognoses and are typically not offered potentially curative transplant as an option, largely because salvage treatments have a limited ability to produce a complete remission, which is necessary prior to conventional BMT if conventional BMT is to be successful. However, with Iomab-B targeted conditioning, a complete remission prior to starting the Iomab-B conditioning is not necessary for a successful transplant. Iomab-B is an ARC or Antibody Radiation-Conjugate that targets CD45, an antigen expressed on leukemia, lymphoma and immune cells, and delivers Iodine-131 that kills targeted cells via linear energy transfer. Key highlights from the SIERRA Trial presented at ASH (Free ASH Whitepaper) and the TCT Meetings include:

Initiated Actimab-A venetoclax combination trial. This novel Phase 1/2 trial will study Actimab-A in combination with venetoclax for patients with relapsed or refractory AML or Acute Myeloid Leukemia. Venetoclax is a BCL-2 or B-Cell Lymphoma 2 inhibitor, BCL-2 is one of several proteins encoded by the BCL2 gene family, which regulates apoptosis or programmed cell death. Venetoclax is jointly developed and marketed by AbbVie and Genentech and is approved for patients with CLL or Chronic Lymphocytic Leukemia, and SLL or Small Lymphocytic Leukemia and AML with an HMA or hypomethylating agent.
Response rates of relapsed or refractory patients with AML to venetoclax as a single agent have been reported to be 19%. In a recent webinar, Actinium highlighted that one study observed that of 21 relapsed or refractory AML patients that responded to venetoclax and an HMA, 13 (62%) stopped venetoclax treatment with disease progression being the most common reason for discontinuation. The study also observed that no patients with secondary AML responded to treatment with venetoclax and patients with FLT3 mutations had lower response rates.

MCL-1 is another protein encoded by the BCL2 gene family that is also overexpressed in cancers, including relapsed or refractory AML, that prevents apoptosis and promotes resistance to venetoclax, which does not bind to MCL-1. It has been observed that MCL-1 levels can be depleted with radiation, but only external radiation was used in these studies. Actinium is studying the use of targeted internalized radiation from Actimab-A to deplete MCL-1 levels thereby removing the AML cells’ resistance mechanism and rendering them more susceptible to venetoclax. Actimab-A is an ARC that delivers internalized radiation from the alpha-particle emitting isotope Ac-225 or Actinium-225 via the CD33 targeting monoclonal antibody lintuzumab

Actinium is conducting this combination study with the goal of offering a therapy to patients that do not respond or stop responding to venetoclax. In addition to the potential to deplete MCL-1 levels, Actimab-A’s radiation mechanism of action is agnostic to cytogenetic mutations and has shown to produce responses in patients with secondary AML. Actinium is also planning a Phase 1/2 trial that will study Actimab-A in combination with venetoclax and a hypomethylating agent. This triplet trial will also enroll patients with relapsed or refractory AML and is expected to initiate in the first half of 2019.

Advanced to second patient cohort in Actimab-A CLAG-M trial. Actinium is also studying Actimab-A in combination with the salvage chemotherapy regimen CLAG-M (cladribine, cytarabine, filgrastim, and mitoxantrone) in patients with relapsed or refractory AML. Chemotherapy and radiation are routinely used in combination together with a majority of patients receiving external beam radiation. However, patients with AML are not treated with external radiation as the diffuse nature of the disease prohibits therapeutic levels of radiation from being used due to safety and toxicity concerns. Ac-225 is a potent isotope capable of causing lethal double stranded breaks in cell DNA but its energy is limited to a few cell diameters. CD33 is an antigen expressed on the surface of a vast majority of AML cells. This trial is evaluating the effect targeted internalized radiation via Actimab-A will have in combination with CLAG-M on safety and tolerability, response rates, rates of BMT, PFS or progression-free survival, and OS or overall survival.
In the first dose cohort, patients received 0.25 uCi/kg of Actimab-A. This combination trial is designed as a 3+3 dose escalation study. No DLT’s or dose limiting toxicities were reported in the first patient cohort. As a result, and per the study protocol, the Institutional Review Board (IRB) at MCW authorized the initiation of the second dosing cohort, in which patients are receiving 0.50 uCi/kg of Actimab-A. Assuming no DLTs are observed in the second cohort, three patients will be treated and the study will progress to the third and final cohort that will study Actimab-A at a dose of 0.75 uCi/kg.

Advanced to second module of collaborative research program with Astellas Pharma, Inc. (Astellas). The Company’s previously announced research collaboration with Astellas is using its AWE or Antibody Warhead Enabling technology platform to conjugate and label select Astellas targeting agents with the potent Ac-225 payload. In January 2019, Actinium announced that it completed the first module of the collaboration and the second module had been initiated. Since launching its AWE Program in November 2017, Actinium has achieved the following milestones:
Appointed Dr. Dale Ludwig, a leading antibody therapeutics and antibody conjugate expert, as Chief Scientific Officer
Presented positive data at ASH (Free ASH Whitepaper) 2017 demonstrating the superior in vitro cell killing properties of Ac-225 labeled daratumumab or Darzalex, Johnson & Johnson’s blockbuster CD38 targeting therapy for multiple myeloma
Presented additional positive data from in vivo animal studies at AACR (Free AACR Whitepaper) 2018 demonstrating enhanced tumor control and survival with Ac-225 labeled daratumumab
Significantly strengthened senior leadership team in core areas. Appointed Cynthia Pussinen as Executive Vice President of Technical Operations and Supply Chain. Ms. Pussinen brings 25 years of highly relevant experience to Actinium gained at Pfizer and Ipsen Biosciences, Inc. Most recently, she was Head of Strategic Portfolio Management, Worldwide Research & Development. In this role she led efforts to maximize the value of Pfizer’s pre-Proof of Concept portfolio across 6 research units, including driving pipeline decision making, portfolio prioritization and clinical portfolio investment efforts across the R&D organization. Previously, President and General Manager of Ipsen Biosciences, Inc. where she led the operational and strategic directions of this subsidiary company, including maintaining an annual operating budget of more than $100 million, and managing two sites with more than 220 employees.
Appointed Qing Ling, PhD, DABR to newly created position of Vice President, Head of Radiation Sciences. This newly created position will drive innovation in line with Actinium’s strategic vision related to its AWE technology platform. Dr. Liang will collaborate closely with clinical trial sites and their staffs, regulators and other key stakeholders to help advance and optimize Actinium’s clinical ARC programs to deliver the best possible outcomes for patients. Dr. Liang is a Medical Physicist certified by the American Board of Radiology and prior to Actinium was Medical Physicist and Assistant Professor at Fox Chase Cancer Center at Temple University (Philadelphia, PA). Prior to that, she had worked at Mercy Health System (Janesville, WI), Turville Bay MRI & Radiation Oncology (Madison, WI), University of Wisconsin Hospital (Madison, WI), and UW Accredited Dosimetry Calibration Laboratory (Madison, WI).

Appointed Mamata Gokhale, PhD, RAC as Vice President, Global Head of Regulatory Affairs. Dr. Gokhale brings over 20 years of regulatory affairs experience to Actinium that began at the FDA as a reviewer before transitioning to industry where she worked at biotechnology and pharma companies including Amgen, Watson Pharma, Neumedicines Inc. and global Contract Research Organizations including Voisin Consulting Life Sciences and Paraxel International. At Amgen Dr. Gokhale successfully contributed to approvals and expansion of Prolia , Xgeva , Vectibix and Sensipar . Dr. Gokhale’s regulatory experience includes developing regulatory strategies for small molecules, monoclonal antibodies, cell and gene therapies, leading and managing regulatory interactions, requesting orphan drug, breakthrough therapy and fast track designations and pediatric vouchers, resolution of clinical hold issues, developing target product profiles, core data sheets and conducting labeling negotiations.

Significantly expanded patent portfolio. Through rejuvenated R&D activity Actinium’s patent portfolio has increased to a total of 111 issued and pending patents in the U.S. and internationally, which is up from the 75 reported previously. This intellectual property portfolio, contained within 28 patent families, covers key areas of Actinium’s business. The estate covers ARC generation, composition of matter, formulations, and methods of administration for solid and liquid cancers as well as radionuclide production including the manufacturing of Ac-225 or Actinium-225. Actinium’s recent patent filings pertain to its planned pivotal Actimab-MDS targeted conditioning trial, ARC combination trials of Actimab-A with venetoclax and CLAG-M, as well as its next-generation ARC’s resulting from its AWE technology platform. These follow recent patent filings from Actinium related to its Iomab-ACT next generation lymphodepletion program for CAR-T and adoptive cell therapies that includes four pending patents and one provisional patent application for cancer and non-malignant diseases. These new filings are in addition to Actinium’s broad intellectual property and patent portfolio that cover direct labeling, or conjugation and labeling of a biomolecular targeting agent to a radionuclide warhead, and its development and use as a therapeutic regimen for the treatment of diseases such as cancer. Actinium has patents on the use of the "gold standard" chelator DOTA, an organic compound used to attach, or conjugate, the radionuclide Ac-225 to monoclonal antibodies and any conceivable derivative thereof, as well key patents covering the manufacturing of Ac-225 in a cyclotron. In addition, Actinium extensive know-how and trade secrets in the application of its AWE technology platform to support its existing pipeline and potential collaborations.
Research and development expenses for the year ended December 31, 2018 declined by $0.7 million to $17.0 million compared to $17.7 million for the year ended December 31, 2017. The decrease was primarily attributable to the recognition of payments received from Astellas, with such payments accounted for as a reduction in research and development expenses, as well as lower expenses related to Actimab-A and lower non-cash stock-based compensation expense.
General and administrative expenses declined by $2.5 million to $6.7 million for the year ended December 31, 2018 compared to $9.2 million for the year ended December 31, 2017, primarily due to lower compensation expense, resulting from lower non-cash stock-based compensation expense during 2018 and one-time charges paid to certain former employees in 2017.

Actinium reported a cash and cash equivalent balance of $13.6 million as of December 31, 2018. In its Annual Report of Form 10-K which was filed with the Securities and Exchange Commission on March 15, 2018, the Company’s audited financial statements contained a going concern explanatory paragraph in the audit opinion from Marcum LLP, its independent registered public accounting firm.

Net loss decreased by $2.9 million to $23.7 million for the year ended December 31, 2018 compared to $26.6 million for the year ended December 31, 2017. The decrease was primarily due to lower general and administrative expenses and research and development expenses.

Upcoming Conferences
Actinium’s management will present at the Oppenheimer & Co. 29th Annual Healthcare Conference, being held March 19-20. The details of Actinium’s presentation are as follows:

Presentation Details:
Date: Wednesday, March 20, 2019
Time: 1:35 pm Eastern Time
Room: Consulate
Venue: Westin Grand Central Hotel in New York City

In addition, members of Actinium’s executive, clinical, R&D, commercial and CMC teams will be attending the AACR (Free AACR Whitepaper) or American Association of Cancer Research Annual Meeting being held March 29 – April 3 at the Georgia World Congress Center in Atlanta, Georgia and the TAT or 11th International Symposium on Targeted-Alpha-Therapy being held April 1 – 4 at the Fairmont Chateau Laurier in Ottawa, Canada.

On March 19, 2019 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that six abstracts highlighting progress in the Rubraca clinical development and lucitanib preclinical research programs will be presented at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place March 29 – April 3 in Atlanta (Press release, Clovis Oncology, MAR 19, 2019, View Source [SID1234534502]).

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The accepted abstracts summarize multiple clinical trials and nonclinical research in which Rubraca is being studied as single agent and combination therapy in a variety of solid tumor types including pancreatic, ovarian, bladder and prostate. In addition, one abstract summarizes ongoing nonclinical research for lucitanib.

"We are actively evaluating the potential utility of Rubraca and lucitanib in a wide range of solid tumors," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We know that many healthcare professionals and patients are hopeful about the role that these therapies may play in treating these cancers, and we are pleased to share our latest updates at this year’s AACR (Free AACR Whitepaper) meeting."

The five Clovis Oncology-sponsored presentations and one presentation of an investigator-initiated trial comprise:

Abstract CT234 – A Phase II, single arm study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic mutation in BRCA1, BRCA2 or PALB2

Presenter: Kim A. Reiss Binder
Session: CTMS03 Developmental Therapeutics: Clinical Results of Novel Agents
Date/Time: April 2, 2019, 3:35 – 3:50 PM EDT
Location: Marcus Auditorium- Bldg. A-GWCC
Abstract 727 (Poster 1) – Comprehensive genomic profiling of >1000 plasma and tumor tissue samples from metastatic castration-resistant prostate cancer (mCRPC) patients gives insight into targeted treatment strategies

Presenter: Foad Green
Session: Molecular and Cellular Biology/Genetics; Cancer Genomics 1
Date/Time: Sunday, March 31, 2019 from 1:00 – 5:00 PM EDT
Location: Exhibit Hall B, Section 33
Abstract 1214 (Poster 11) – Enhancement of anti-PD-1 antitumor efficacy in syngeneic preclinical models by the angiogenesis inhibitor lucitanib

Presenter: Rachel L. Dusek
Session: Experimental and Molecular Therapeutics; Cancer Immunotherapy
Date/Time: Monday, Apr 1, 2019 8:00 AM – 12:00 PM EDT
Location: Exhibit Hall B, Section 10
Abstract 3888 (Poster 8) – Intracranial evaluation of the in vivo pharmacokinetics, brain distribution, and efficacy of rucaparib in BRCA-mutant, triple-negative breast cancer

Presenter: Minh Nguyen
Session: Experimental and Molecular Therapeutics; Pharmacokinetics and Pharmacodynamics / Preclinical Toxicology
Date/Time: Tuesday, Apr 2, 2019 1:00 – 5:00 PM
Location: Exhibit Hall B, Section 13
Abstract CT158 (Poster 2) – ATHENA (GOG-3020/ENGOT-ov45): a randomized, double-blind, placebo-controlled, Phase III study of rucaparib + nivolumab following front-line platinum-based chemotherapy in ovarian cancer

Presenter: Shannon N. Westin
Session: Phase I-III Trials in Progress: Part 2
Date/Time: Tuesday, Apr 2, 2019 8:00 AM – 12:00 PM EDT
Location: Exhibit Hall B, Poster Section 17
Abstract CT179 (Poster 23) – ATLAS: A Phase II, open-label study of rucaparib in patients with locally advanced or metastatic urothelial carcinoma

Presenter: Petros Grivas
Session: Phase I-III Trials in Progress: Part 2
Date/Time: Tuesday Apr 2, 2019 8:00 AM – 12:00 PM EDT
Location: Exhibit Hall B, Poster Section 17
The five Clovis-sponsored posters will be available online at View Source at once they are presented at the meeting.

About Rubraca (rucaparib)

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian, metastatic castration-resistant prostate, and bladder cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Rubraca U.S. FDA Approved Indications

Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Rubraca is indicated as monotherapy for the treatment of adult patients with deleterious BRCA mutations (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies and selected for therapy based on an FDA-approved companion diagnostic for Rubraca.

Select Important Safety Information

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) occur uncommonly in patients treated with Rubraca, and are potentially fatal adverse reactions. In approximately 1100 treated patients, MDS/AML occurred in 12 patients (1.1%), including those in long-term follow-up. Of these, five occurred during treatment or during the 28-day safety follow-up (0.5%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 28 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA-damaging agents. Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1).

Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose (see Dosage and Administration [2.2] in full Prescribing Information) and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks, or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample cytogenetic analysis. If MDS/AML is confirmed, discontinue Rubraca.

Based on its mechanism of action and findings from animal studies, Rubraca can cause fetal harm when administered to a pregnant woman. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Rubraca.

Most common adverse reactions in ARIEL3 (≥ 20%; Grade 1–4) were nausea (76%), fatigue/asthenia (73%), abdominal pain/distention (46%), rash (43%), dysgeusia (40%), anemia (39%), AST/ALT elevation (38%), constipation (37%), vomiting (37%), diarrhea (32%), thrombocytopenia (29%), nasopharyngitis/upper respiratory tract infection (29%), stomatitis (28%), decreased appetite (23%) and neutropenia (20%).

Most common laboratory abnormalities in ARIEL3 (≥ 25%; Grade 1–4) were increase in creatinine (98%), decrease in hemoglobin (88%), increase in cholesterol (84%), increase in alanine aminotransferase (ALT) (73%), increase in aspartate aminotransferase (AST) (61%), decrease in platelets (44%), decrease in leukocytes (44%), decrease in neutrophils (38%), increase in alkaline phosphatase (37%) and decrease in lymphocytes (29%).

Most common adverse reactions in Study 10 and ARIEL2 (≥ 20%; Grade 1–4) were nausea (77%), asthenia/fatigue (77%), vomiting (46%), anemia (44%), constipation (40%), dysgeusia (39%), decreased appetite (39%), diarrhea (34%), abdominal pain (32%), dyspnea (21%) and thrombocytopenia (21%).

Most common laboratory abnormalities in Study 10 and ARIEL2 (≥ 35%; Grade 1–4) were increase in creatinine (92%), increase in alanine aminotransferase (ALT) (74%), increase in aspartate aminotransferase (AST) (73%), decrease in hemoglobin (67%), decrease in lymphocytes (45%), increase in cholesterol (40%), decrease in platelets (39%) and decrease in absolute neutrophil count (35%).

Co-administration of Rubraca can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring. Because of the potential for serious adverse reactions in breast-fed children from Rubraca, advise lactating women not to breastfeed during treatment with Rubraca and for 2 weeks after the last dose. You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Clovis Oncology, Inc. at 1-844-258-7662.

Click here or full Prescribing Information and additional Important Safety Information.

Rubraca ▼ (rucaparib) EU Authorized Use and Important Safety Information

Rucaparib is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

Rucaparib is indicated as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Summary warnings and precautions: Haematological toxicity: Patients should not start Rubraca until they have recovered from haematological toxicities caused by previous chemotherapy (≤ CTCAE Grade 1). Complete blood count testing prior to starting treatment with Rubraca and monthly thereafter is advised. Rubraca should be interrupted or dose reduced and blood counts monitored weekly until recovery for the management of low blood counts. Myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML): If MDS/AML is suspected, the patient should be referred to a haematologist for further investigation. If MDS/AML is confirmed, Rubraca should be discontinued. Photosensitivity: Patients should avoid spending time in direct sunlight as they may burn more easily. When outdoors, patients should wear protective clothing and sunscreen with SPF of 50 or greater. Gastrointestinal toxicities: Low grade (CTCAE Grade 1 or 2) nausea and vomiting may be managed with dose reduction or interruption. Additionally, antiemetics may be considered for treatment or prophylaxis.

Click here to access the current Summary of Product Characteristics. Healthcare professionals should report any suspected adverse reactions via their national reporting systems.

About Lucitanib

Lucitanib is an oral, potent inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor receptors alpha and beta (PDFGRα/β) and fibroblast growth factor receptors 1 through 3 (FGFR1-3).

Emerging clinical data support the combination of angiogenesis inhibitors and immunotherapy to increase effectiveness in multiple cancer indications. Angiogenic factors, such as vascular endothelial growth factor (VEGF), are frequently up-regulated in tumors and create an immunosuppressive tumor microenvironment. Use of antiangiogenic drugs reverses this immunosuppression and can augment response to immunotherapy.

Lucitanib is an unlicensed medical product.

On March 19, 2019 OncBioMune Pharmaceuticals, Inc. (OTCQB:OBMP) ("OncBioMune" or the "Company"), a clinical-stage biopharmaceutical company engaged in the development of a proprietary therapeutic prostate cancer vaccine immunotherapy and CD71-targeted cancer therapy, reported that the Phase 2, randomized study of ProscaVax in treatment-naïve patients with clinically localized prostate cancer vs active surveillance is now open for enrollment (Press release, Oncbiomune, MAR 19, 2019, View Source [SID1234534458]).

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The first open site is Beth Israel Deaconess Medical Center, a member of the Dana-Farber/Harvard Cancer Center and a teaching hospital of Harvard Medical School in Boston, MA.

Although many patients with low-risk localized prostate cancer can be safely monitored with an Active Surveillance strategy in lieu of up-front treatment with surgery or radiation, about half of these patients will ultimately have to undergo treatment due to worsening of their disease. Thus, patients with localized prostate cancer need improved therapies to help prevent worsening of their disease and avoid the side effects of surgery or radiation. This study will evaluate the safety and efficacy of ProscaVax (Prostate-specific antigen (PSA) / Interleukin-2 (IL-2) / Granulocyte-macrophage colony-stimulating factor (GM-CSF)), the Company’s flagship therapeutic cancer vaccine, in patients with localized prostate cancer compared to patients monitored on Active Surveillance.

"In general, this population of patients have two very different options. Either go into active surveillance waiting to see if there is progression of their cancer or have intensive local therapy, which can leave these patients with significant side effects. The goal which we are trying to obtain with this immunotherapy approach is to give these patients a third option which has more intervention than Active Surveillance but with less toxicity than surgery, radiation therapy, or hormonal therapy," commented Dr. Brian Barnett, Chief Executive Officer at OncBioMune. "Phase 1 data underscores a strong safety profile for ProscaVax, while potentially moderating disease progression as measured by PSA doubling time. The start of this study represents a major milestone for our company."

The Phase 2 study (randomized 2:1, treatment arm:control group) will enroll 120 adult patients with clinically localized prostate cancer who have received no prior therapy for prostate cancer. For the purpose of this study the primary endpoint will be an analysis of the number and percent of patients with progression at two years in each arm. Statistical assumptions are a 35% progression rate within two years in the control arm and decrease to 15% progression rate in the treatment arm.

On March 19, 2019 TESARO, an oncology-focused business acquired by GlaxoSmithKline plc (LSE/NYSE: GSK), reported the presentation of data from the Phase 1/2 GARNET study evaluating dostarlimab in women with recurrent or advanced endometrial cancer who progressed on or after a platinum-based regimen (Press release, GlaxoSmithKline, MAR 19, 2019, View Source [SID1234534481]). These data were presented at the 2019 Society for Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer in Honolulu, Hawaii. The preliminary results demonstrate clinically meaningful and durable response rates of dostarlimab (anti-PD-1 antibody, formerly TSR-042), in this patient population, regardless of microsatellite instability status. In addition, the safety findings indicate that dostarlimab is well tolerated with a safety profile consistent with what is expected of anti-PD-1 therapy.

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Further data from the GARNET study will be analysed using the RECIST 1.1 criteria to support regulatory filing for dostarlimab in endometrial cancer at the end of 2019.

Mary Lynne Hedley, Ph.D., President and Chief Operating Officer of TESARO, said, "Currently, treatment options for women with advanced or recurrent endometrial cancer are limited, with only one FDA-approved agent for a subset of these patients. We intend to use these and other data from the GARNET study to seek regulatory approval of dostarlimab to potentially address the critical unmet treatment needs of women whose disease has progressed. The data presented today evaluating dostarlimab in women with recurrent/advanced endometrial cancer, combined with earlier data in patients with non-small cell lung cancer, reinforces the potential of dostarlimab in treating patients with a variety of solid tumours."

Endometrial cancer (EC) is the most common gynaecologic malignancy in the U.S. There are limited treatment options for women whose disease progresses on or after first-line therapy. EC can be classified as microsatellite stable (MSS/75%) or microsatellite instability-high (MSI-H/25%). Currently, there is only one approved therapy in the recurrent EC setting for the subset of patients with MSI-H tumours, and no approved treatments for patients with MSS EC who have recurred after platinum-based chemotherapy.

Key Study Findings
A total of 125 patients were analysed including 41 MSI-H (33%), and 79 MSS (63%) patients, as well as 5 with an unknown MSI-status (4%). Dostarlimab was dosed at 500 mg once every 3 weeks for 4 doses, followed by 1000 mg once every 6 weeks until disease progression.

Determination of MSI status was made based upon a central test using next generation sequencing (NGS). Treatment with dostarlimab monotherapy resulted in a clinically meaningful response rate in recurrent or advanced EC who progressed on or after a platinum-based regimen, regardless of MSI status. Overall response rates by irRECIST in the full population, MSI-H population, and MSS population were 30%, 49%, and 20%, respectively. Disease control rate in the full population, MSI-H population, and MSS population was 53%, 63% and 47%, respectively.

At the time of data cutoff, treatment was still ongoing in 84% of responders, with 89% of the responders (33 of 37) having been on treatment for more than six months and 49% of responders (18 of 37) having been on treatment for more than one year. Durability of response was similar between the MSI-H and MSS cohorts. The median duration of response (DOR) has not yet been reached. All responses were assessed using irRECIST criteria.

The data show that 88 out of 125 (70.4%) patients had at least 1 treatment-emergent adverse event (TEAE). The most commonly reported TEAEs related to dostarlimab were fatigue (14.4%), diarrhea (12.8%), and nausea (12.0%). In general, adverse events were low grade, with only 13.6% of patients experiencing grade 3 or higher adverse events. No deaths occurred due to a treatment-related adverse event. In total, 5.6% of all patients experienced a grade 3 or higher immune related, treatment-related adverse event.

About GARNET
The ongoing Phase 1/2 GARNET trial is evaluating dostarlimab as monotherapy in patients with advanced solid tumours. GARNET included a weight-based dose escalation study (Part 1) and a fixed-dose safety study (Part 2A), both of which have been completed. Results of these studies were used to determine the recommended Phase 2 dose (RP2D; 500 mg Q3W for the first 4 cycles then 1000 mg Q6W). Part 2B of the study includes four expansion cohorts: MSI-H endometrial cancer, MSI-H non-endometrial cancer, MSS endometrial cancer, and non-small cell lung cancer (NSCLC). Data from the NSCLC cohort have been previously presented at Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in 2018.

About dostarlimab
Dostarlimab (TSR-042) is an investigational humanized anti-programmed death (PD)-1 monoclonal antibody that binds with high affinity to the PD-1 receptor and effectively blocks its interaction with the ligands PD-L1 and PD-L2. If approved, dostarlimab would be the first anti PD-1 therapy administered as monotherapy every 3 weeks for 4 doses then every 6 weeks thereafter. Dostarlimab was developed as part of a collaboration between TESARO and AnaptysBio, Inc. This collaboration was initiated in March of 2014, and is focused on the development of monospecific antibody drugs targeting PD-1, TIM-3 (TSR-022), and LAG-3 (TSR-033), in addition to a bi-specific antibody drug candidate targeting PD-1/LAG-3 (TSR-075).

Dostarlimab is not currently approved for use anywhere in the world.

On March 19, 2019 Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of stem cell transplant to more patients, reported financial results and business highlights for the fourth quarter and full year ended December 31, 2018 (Press release, Magenta Therapeutics, MAR 19, 2019, View Source [SID1234534504]).

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"2018 was a transformative year for Magenta, as we progressed our first-in-class programs and achieved multiple clinical and preclinical milestones," said Jason Gardner, D.Phil., Chief Executive Officer and President, Magenta Therapeutics. "As we begin 2019, Magenta is the only company addressing the major barriers to stem cell transplant and gene therapy, with the goal of changing the lives of patients with autoimmune diseases, blood cancers and genetic diseases through curative therapies. We are looking forward to building on this progress as we advance our conditioning, mobilization and cell therapy programs."

Upcoming Anticipated Milestones:

The Company plans to achieve the following key milestones in 2019:

Present preclinical data on C100 anti-CD45 targeted conditioning program in autoimmune diseases and declare development candidate

Present preclinical data on C200 anti-CD117 targeted conditioning in gene therapy, and advance development candidate

Begin Phase 1 study of MGTA-145 first-line mobilization agent in healthy volunteers in the first half of 2019, and present clinical data in the second half of 2019

Present additional clinical data from the Phase 2 study of MGTA-456 in IMDs

Recent Business Highlights:

Updated preclinical data for C100 conditioning program showed potent depletion of hematopoietic stem cells and immune cells: At the Transplant and Cellular Therapy (TCT) meeting in February 2019, Magenta presented data from its C100 targeted conditioning program, showing potent stem and immune cell depletion with an anti-CD45 amanitin antibody-drug conjugate (ADC) that was well tolerated at efficacious doses in non-human primates. The Company expects to declare a development candidate for this program in 2019 and intends to develop C100 in both autoimmune diseases and blood cancers.

Declared development candidate in C200 targeted conditioning program and presented preclinical data: At the end of 2018, Magenta declared a development candidate in its C200 targeted conditioning program, which is designed to deplete stem cells in the bone marrow. The Company presented data at the TCT meeting in February 2019 on the development candidate, an anti-CD117 amanitin ADC, showing that it potently and selectively depleted hematopoietic stem cells in non-human primates while preserving the immune system. The ADC was well tolerated at the efficacious doses. Magenta has begun investigational new drug (IND)-enabling studies with this ADC and plans to develop it as a conditioning agent for stem cell gene therapy, in patients with genetic disorders such as sickle cell disease, where current conditioning regimens are toxic.

Updated preclinical data for MGTA-145 first-line mobilization therapy showed differentiated efficacy from standard of care: In data presented at the TCT meeting in February 2019, Magenta showed that a single dose of MGTA-145 plus plerixafor mobilized two to three times more stem cells in non-human primates than a multi-day regimen of current standard of care, G-CSF. The cells mobilized with MGTA-145 plus plerixafor rapidly engrafted in non-human primates following autologous transplant. A subset of the MGTA-145-mobilized cells from non-human primates was also shown to suppress graft-vs.-host-disease and extend survival in preclinical models. The company expects to initiate a Phase 1 study of MGTA-145 in the first half of 2019 and share clinical results in the second half of 2019.

Updated clinical data for MGTA-456 cell therapy showed early signs of clinical benefit in IMDs: Magenta presented updated data from the Phase 2 clinical study of MGTA-456 in patients with IMDs at the TCT meeting in February 2019. Patients with cerebral adrenoleukodystrophy (cALD) treated with MGTA-456 in the study showed persistent resolution of brain inflammation and stable disease scores. Patients with Hurler syndrome treated with MGTA-456 showed correction of enzyme deficiency and decrease in toxic metabolites. These early clinical benefits are associated with improved long-term disease outcomes in patients undergoing stem cell transplant for IMDs. The Company will next present data from this study at the American Academy of Neurology (AAN) annual meeting in May. A Phase 2 investigator-initiated study of MGTA-456 in blood cancers began in December 2018. After careful review of comprehensive transplant outcomes data in sickle cell disease, the Company will evaluate development of MGTA-456 in sickle cell disease as less toxic conditioning becomes available.

Fourth Quarter Financial Results:

Cash Position: Cash, cash equivalents and marketable securities as of December 31, 2018, were $142.6 million compared to $51.4 million on December 31, 2017. The increase is primarily driven by net proceeds from the $52.2 million Series C preferred stock financing completed in April 2018, and net proceeds of $89.9 million from Magenta’s IPO completed in June 2018, offset by $57.6 million in net loss during 2018. Magenta anticipates that its cash, cash equivalents and marketable securities will be sufficient to fund operations and capital expenditures through 2020 on the Company’s current business plan.

Research and Development Expenses: Research and development (R&D) expenses were $12.4 million in the fourth quarter of 2018, compared to $5.6 million for the same period in 2017. The increase was primarily due to increased costs related to drug discovery efforts in our conditioning programs, preclinical costs, toxicology studies and manufacturing to support our mobilization program, the advancement of the MGTA-456 Phase 2 clinical trial, continued progression of the Company’s pipeline and increased costs associated with the growth of the Company.

General and Administrative Expenses: General and administrative (G&A) expenses were $5.5 million for the fourth quarter of 2018, compared to $2.6 million for the same period in 2017. The increase was primarily due to increased G&A personnel and facility costs associated with the growth of the Company.

Net Loss: Net loss was $16.7 million for the fourth quarter of 2018, compared to net loss of $8.0 million for the same period in 2017.