On November 28, 2018 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a company focused on the development of novel immunotherapies based on proprietary chimeric antigen receptor engineered T cell ("CAR T") technology and gene therapies for rare diseases, reported that additional safety and efficacy Phase 1 data evaluating MB-102 (CD123 CAR) in relapsed or refractory acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN) have been selected for an oral presentation at the AACR (Free AACR Whitepaper) Special Conference on Tumor Immunology and Immunotherapy (Press release, Mustang Bio, NOV 28, 2018, View Source [SID1234531653]). The presentation will take place on November 30, 2018, in Miami Beach, Florida.

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Martina Sersch, M.D., Ph.D., Chief Medical Officer of Mustang, said, "We are excited about the additional data demonstrating MB-102’s (CD123 CAR T) potential to treat patients with AML and BPDCN. Initial safety and tolerability data as well as preliminary data on efficacy are very promising in a population with high unmet medical need. Based on the Phase 1 data, we expect to submit an IND filing for MB-102 and look forward to initiating a multicenter Phase 1/2 clinical trial in 2019 in patients with AML, BPDCN and high-risk myelodysplastic syndrome."

Lihua Elizabeth Budde, M.D., Ph.D., assistant professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope and principal investigator for the Phase 1 trial, said, "There is increased expression of CD123 on AML blasts, leukemic stem cells and BPDCN cells compared to normal hematopoietic stem cells, and it is therefore a promising target for cellular immunotherapy. We remain encouraged by interim data showing MB-102’s potential to treat BPDCN and AML and continue to evaluate MB-102’s clinical benefits in our ongoing Phase 1 clinical trial."

Details of the oral presentation are as follows:

Title: CD123CAR Displays Clinical Activity in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) and Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): Safety and Efficacy Results from a Phase 1 Study
Special Session: Novel Targets, Pathways and Tools
Date and Time: Friday, November 30, 2018; 8:00 AM – 9:30 AM ET
Location: Loews Miami Beach Hotel
Presenter: Elizabeth Lihua Budde, M.D., Ph.D., City of Hope, Duarte, CA

For more information, please visit: View Source;ItemID=733&DetailItemID=733.

Key Efficacy and Safety Findings
This single center, first-in-human Phase 1 dose-escalation clinical trial is evaluating the safety and activity of escalating doses of MB-102 in patients with relapsed or refractory AML (cohort 1) and BPDCN (cohort 2). Patients receive a single dose of MB-102 with an option for a second infusion if they continue to meet safety and eligibility criteria and still have CD123+ disease. To date, 18 patients have been enrolled and nine have been treated (seven with AML, two with BPDCN).

In the AML cohort, all seven patients had at least one prior allogeneic stem cell transplant and median of 4 (range: 4-10) prior lines of therapy. Two patients were treated at dose level 1 (50M CAR+ T). Trial investigators reported that one achieved a morphologic leukemic-free state (MLFS) that lasted 70 days. This patient received a second infusion three months later, with blast reduction from 77.9% to 0.9% (flow cytometry) after 35 days. Five patients received dose level 2 (200M CAR+ T). One patient achieved complete remission (CR) with incomplete count recovery at day 28, and one patient achieved MLFS that improved to CR at day 84. The remaining three patients had stable disease.

In the BPDCN cohort, two patients were treated with 100M CAR+ T and tolerated the treatment well, with no grade 3 or above treatment-related toxicities. One patient achieved CR with no evidence of disease in the bone marrow and skin at day 28.

Investigators found MB-102 infusions of up to 200M CAR T cells were safe. All toxicities observed to date were reversible and manageable. No patient developed grade 3 or above cytokine release syndrome or neurotoxicity. There were no treatment-related dose-limiting toxicities and no treatment-related cytopenias longer than 12 weeks. One patient with prior cutaneous graft-versus-host disease developed grade 1 rash five weeks after CAR T infusion, which resolved after clinical management. Peak of T cell expansion occurred within the first 14 days. Investigators did not observe any CD123-loss leukemic variants.

About Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells characterized by rapid growth of abnormal white blood cells that accumulate in the bone marrow. Although AML is rare, there are approximately 20,000 new cases in the U.S. each year and 10,000 deaths. Current treatment of relapsed or refractory AML with chemotherapy or hematopoietic stem cell transplantation is associated with low rates of complete response and considerable complications.

CD123 is overexpressed on AML blasts and leukemic stem cell-enriched cell subpopulations compared to normal hematopoietic stem cells and myeloid progenitors, making CD123 an attractive target for T cell-based adoptive immunotherapy.

About Blastic Plasmacytoid Dendritic Cell Neoplasm
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and incurable blood cancer with a median survival of less than 18 months and no standard of care. High levels of CD123 expression is one of the diagnostic hallmarks of BPDCN, making CD123 an attractive target for T cell-based adoptive immunotherapy.

About MB-102 (CD123 CAR T)
MB-102 (CD123 CAR T) is a CAR T cell therapy that is produced by engineering patient T cells to recognize and eliminate CD123-expressing tumors. CD123 is widely expressed on bone marrow cells of patients with MDS, as well as in hematologic malignancies including AML, B cell acute lymphoblastic leukemia, hairy cell leukemia, BPDCN, chronic myeloid leukemia and Hodgkin’s lymphoma.

In the first-in-human clinical trial at City of Hope (NCT02159495), MB-102 has demonstrated complete responses at low doses in AML and BPDCN without dose-limiting toxicities, as reported at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2017. Dose escalation continues at City of Hope in both indications.

On November 28, 2018 Varian (NYSE: VAR) reported its Halcyon system has been approved by the China National Medical Product Administration (NMPA), which allows the company to market this new cancer treatment system in China (Press release, Varian Medical Systems, NOV 28, 2018, View Source [SID1234531710]). This approval further expands the global availability of Halcyon and access to high-quality, cost-effective cancer treatments.

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As an advanced cancer treatment system with a human-centered and user-friendly design, Halcyon is engineered to revolutionize clinical workflow, accelerate installation timeframes, expedite commissioning, simplify training, and automate treatment. The system is well suited to treat cancer patients with radiotherapy, offering advanced treatments for lung, prostate, breast, head & neck, and many other forms of cancer.

"We are very excited to further expand the Halcyon system’s global availability," said Chris Toth, president Varian Oncology Systems. "With the most recent announcement by the Chinese government for expanding Category B licenses and enabling County hospital oncology services availability, Halcyon is a perfect fit."

Halcyon has already received FDA 510(k) clearance in the US, CE mark in Europe, Shonin approval in Japan, ANVISA registration in Brazil, Atomic Energy Regulatory Board (AERB) Certificate for Import and Supply as well as Type Approval in India and TFDA approval in Taiwan since its launch in May 2017.

On November 28, 2018 MabVax Therapeutics Holdings, Inc. (OTC Pink: MBVX), a clinical-stage biotechnology company focused on the development of antibody-based products to address unmet medical needs in the treatment of cancer and pancreatitis, reported that the Company had entered into an equity purchase agreement with Triton Funds LP, a Delaware limited partnership ("Triton Funds"), in which Triton Funds has agreed to purchase up to $1,000,000 of the Company’s to be designated Series P Convertible Preferred Stock, par value of $0.01 per share (the "Series P Preferred Stock"), subject to the effectiveness of an S-1 registration statement that the Company filed with the Securities and Exchange Commission (the "SEC") on November 20, 2018, that registers shares of common stock upon conversion of the Series P Preferred Stock (the "Equity Purchase Agreement") (Press release, MabVax, NOV 28, 2018, View Source [SID1234531673]). Under the terms of the Equity Purchase Agreement, Triton Funds is able to convert the Series P Preferred Stock into common stock at a rate based on the 5-day volume-weighted average price prior to the conversion date, or the stated market purchase price, times 75%. In addition, we agreed to issue 175,000 shares of common stock to Triton Funds LLC, manager of Triton, upon execution of the Equity Purchase Agreement to support the cost of the student-run fund. The summary above is subject to and qualified in its entirety to the Company’s filing of a registration statement on Form S-1 which can be found at:

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Dmitriy Slobodskiy Jr, Research Analyst of Triton Funds, stated, "Here at Triton Funds we strive to locate and invest into companies that make a meaningful impact on significant unmet medical needs. MabVax Therapeutics is one of the cases where a company is developing novel treatments for deadly and debilitating diseases of the pancreas, a small organ that plays a large role in human health."

Sam Yaffa, Founder of Triton Funds, stated, "One of the key factors we look for before we invest is how effective is the management team in advancing the company’s technology, and the team at MabVax has proved to be persistent in its efforts to provide benefits to patients in need of new therapies for unmet medical needs."

President and CEO J. David Hansen, stated, "We are pleased and honored that Triton Funds became interested in MabVax and its clinical stage human antibody development programs for the diagnosis and treatment of pancreatic cancer, and more recently for the development and testing of a clinical stage antibody for the treatment of pancreatitis. We intend to use these proceeds for developing a proof of concept clinical trial protocol for the treatment of pancreatitis using the Company’s antibody designated as MVT-5873 and for general corporate and working capital purposes."

On November 29, 2018 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D. "Astellas") reported that the U.S. Food and Drug Administration (FDA) approved XOSPATA (generic name: gilteritinib) for the treatment of adult patients who have relapsed or refractory (resistant to treatment) Acute Myeloid Leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test.2 XOSPATA is an oral therapy and the first and only FLT3-targeting therapy to be approved by the FDA for this population (Press release, Astellas, NOV 28, 2018, View Source [SID1234531692]).

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The American Cancer Society estimates that in 2018, approximately 19,000 people will be diagnosed with AML in the U.S.3 AML has been associated with various genetic mutations. XOSPATA has demonstrated inhibitory activity against two different mutations, FLT3 internal tandem duplication (ITD) and FLT3 tyrosine kinase domain (TKD).2 Impacting approximately 30 percent of AML patients,4 the FLT3-ITD mutation is associated with worsened disease free survival and overall survival.5,6 FLT3-TKD mutations impact approximately 7 percent of AML patients4 and, although the impact of these mutations is less clear,7 they have been associated with treatment resistance.8

"Our ability to use precision medicine to help patients with FLT3-mutated AML takes an important step forward with the approval of XOSPATA," said Alexander Perl, M.D., Abramson Cancer Center, University of Pennsylvania. "There is an urgent need in the clinic for more targeted agents to help patients whose disease is either refractory to the initial therapy, or who have relapsed."

"XOSPATA offers new hope to patients for whom the treatment path forward is unclear," said Steven Benner, M.D., senior vice president and global therapeutic area head, Oncology Development, Astellas. "For the first time, people with relapsed or refractory FLT3 mutation-positive AML have an FDA approved FLT3-targeting treatment available to them. The approval of XOSPATA is also a proud, landmark moment for our oncology program and marks the first approval of a medicine that will be the cornerstone of our new presence in blood cancers."

The FDA’s approval of XOSPATA was based on the interim analysis of the following endpoints in the ADMIRAL clinical trial: the rate of complete remission (CR)/complete remission with partial hematologic recovery (CRh); the duration of CR/CRh (DOR); and the rate of conversion from transfusion dependence to transfusion independence. The CR/CRh rate was 21%. The median duration of CR/CRh was 4.6 months. The rate of conversion from transfusion dependence to transfusion independence was 31.1% for any 56 day post-baseline period. For patients who achieved a CR/CRh, the median time to first response was 3.6 months (range, 0.9 to 9.6 months). The CR/CRh rate was 29 of 126 in patients with FLT3-ITD or FLT3-ITD/TKD and 0 of 12 in patients with FLT3-TKD only.

Full results from the ADMIRAL trial will be submitted for presentation at an upcoming medical meeting.

The safety evaluation of XOSPATA was based on 292 patients with relapsed or refractory AML treated with 120 mg gilteritinib daily. The median duration of exposure to XOSPATA was 3 months (range 0.1 to 42.8 months). The most frequent non-hematological serious adverse reactions (≥5%) reported in patients were pneumonia (19%), sepsis (13%), fever (13%), dyspnea (7%) and renal impairment (5%). Overall, 22 of 292 patients (8%) discontinued XOSPATA treatment permanently due to an adverse reaction. The most common adverse reactions (>1%) leading to discontinuation were pneumonia (2%), sepsis (2%) and dyspnea (1%). The most common adverse reactions (≥20%) were myalgia/arthralgia (42%), transaminase increased (41%), fatigue/malaise (40%), fever (35%), non-infectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%) and vomiting (20%).

Previously, XOSPATA was granted both Orphan Drug designation9 and Fast Track10 designation by the U.S. FDA. Gilteritinib also received Orphan Designation from the European Commission (EC)11 and Orphan Drug Designation from the Japan Ministry of Health, Labor and Welfare (MHLW).12 The MHLW also granted SAKIGAKE designation to gilteritinib for FLT3mut+ relapsed/refractory AML and approved the treatment for this population in September 2018.13

Astellas reflected the impact from this approval in its financial forecast of the current fiscal year ending March 31, 2019.

About XOSPATA
XOSPATA is indicated for the treatment of adult patients who have relapsed or refractory Acute Myeloid Leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test.2

XOSPATA was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global rights to develop, manufacture and potentially commercialize XOSPATA.

Important Safety Information

Contraindications
XOSPATA is contraindicated in patients with hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactions have been observed in clinical trials.

Warnings and Precautions
Posterior Reversible Encephalopathy Syndrome (PRES) There have been rare reports of PRES with symptoms including seizure and altered mental status with XOSPATA. Symptoms have resolved after discontinuation of XOSPATA. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XOSPATA in patients who develop PRES.

Prolonged QT Interval XOSPATA has been associated with prolonged cardiac ventricular repolarization (QT interval). Of the 292 patients treated with XOSPATA in the clinical trial, 1.4% were found to have a QTc interval greater than 500 msec and 7% of patients had an increase from baseline QTc greater than 60 msec. Perform electrocardiogram (ECG) prior to initiation of treatment with XOSPATA, on days 8 and 15 of cycle 1, and prior to the start of the next two subsequent cycles. Interrupt and reduce XOSPATA dosage in patients who have a QTcF >500 msec. Hypokalemia or hypomagnesemia may increase the QT prolongation risk. Correct hypokalemia or hypomagnesemia prior to and during XOSPATA administration.

Pancreatitis There have been rare reports of pancreatitis in patients receiving XOSPATA in clinical studies. Evaluate patients who develop signs and symptoms of pancreatitis. Interrupt and reduce the dose of XOSPATA in patients who develop pancreatitis.

Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, XOSPATA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 6 months after the last dose of XOSPATA. Advise males with female partners of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 4 months after the last dose of XOSPATA. Pregnant women, patients becoming pregnant while receiving XOSPATA or male patients with pregnant female partners should be apprised of the potential risk to the fetus.

Adverse Reactions
The most frequent non-hematological serious adverse reactions (≥5%) reported in patients were pneumonia (19%), sepsis (13%), fever (13%), dyspnea (7%) and renal impairment (5%).

Overall, 22 of 292 patients (8%) discontinued XOSPATA treatment permanently due to an adverse reaction. The most common adverse reactions (>1%) leading to discontinuation were pneumonia (2%), sepsis (2%) and dyspnea (1%). The most common adverse reactions (≥20%) were myalgia/arthralgia (42%), transaminase increased (41%), fatigue/malaise (40%), fever (35%), non-infectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%) and vomiting (20%).

Other clinically significant adverse reactions occurring in ≤10% of patients included: electrocardiogram QT prolonged (7%), cardiac failure (grouped terms) (4%), pericardial effusion (3%), pericarditis (2%), differentiation syndrome (1%), anaphylactic reaction (1%) and posterior reversible encephalopathy syndrome (1%).

Lab Abnormalities: The most common lab abnormalities (>20%) that were Grade ≥3 that occurred ≥10% were: hypophosphatemia (12%), alanine aminotransferase increased (12%), hyponatremia (12%), aspartate aminotransferase increased (10%).

Drug Interactions
Combined P-gp and Strong CYP3A Inducers: Concomitant use of XOSPATA with a combined P-gp and strong CYP3A inducer decreases XOSPATA exposure which may decrease XOSPATA efficacy. Avoid concomitant use of XOSPATA with combined P-gp and strong CYP3A inducers.

Strong CYP3A inhibitors: Concomitant use of XOSPATA with a strong CYP3A inhibitor increases XOSPATA exposure. Consider alternative therapies that are not strong CYP3A inhibitors. If the concomitant use of these inhibitors is considered essential for the care of the patient, monitor patient more frequently for XOSPATA adverse reactions. Interrupt and reduce XOSPATA dosage in patients with serious or life-threatening toxicity.

Drugs that Target 5HT2B Receptor or Sigma Nonspecific Receptor: Concomitant use of XOSPATA may reduce the effects of drugs that target the 5HT2B receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline). Avoid concomitant use of these drugs with XOSPATA unless their use is considered essential for the care of the patient.

Specific Populations
Lactation: Advise women not to breastfeed during treatment with XOSPATA and for 2 months after the last dose.

Please see Full Prescribing Information for additional safety information.

About the ADMIRAL Trial14
The Phase 3 ADMIRAL trial (NCT02421939) was an open-label, multicenter, randomized study of gilteritinib versus salvage chemotherapy in adult patients with FLT3 mutations who are refractory to or have relapsed after first-line AML therapy. The primary endpoints of the trial are Overall Survival (OS) and complete remission/complete remission with partial hematologic recovery (CR/CRh) rates. The study enrolled 371 patients with FLT3 mutations present in bone marrow or whole blood, as determined by central lab. Subjects were randomized in a 2:1 ratio to receive gilteritinib (120 mg15) or salvage chemotherapy.

On November 28, 2018 WuXi Biologics (2269.HK, WuXi Bio), a leading global open-access biologics technology platform company offering end-to-end solutions for biologics discovery, development and manufacturing, and ABL Bio Corporation (ABL Bio), a privately-held South Korean biotechnology company developing antibody therapeutics for immuno-oncology and neurodegenerative diseases, reported that the companies have entered into an exclusive development and clinical manufacturing partnership for up to 8 antibody therapeutics including ABL Bio’s biologics pipelines and collaboration programs between ABL Bio and I-Mab Biopharma (I-Mab) (Press release, WuXi Biologics, NOV 28, 2018, View Source [SID1234536985]). The agreement showcases the expansive biologics pipeline of ABL Bio and the world leading technical expertise and capabilities of WuXi Biologics in developing bispecific programs.

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"We are very pleased to enter into this partnership with WuXi Biologics. The partnership with WuXi Biologics is an important strategy for growing our internal and external programs of next-generation of biologics such as bispecific antibody. WuXi Biologics has enabled several preclinical and clinical manufacturing programs for ABL Bio as well as collaboration with I-Mab," said Dr. Sang Hoon Lee, Chief Executive Officer of ABL Bio. "I believe that the partnership with WuXi Biologics will bring a synergy effect for developing our bispecific antibody pipelines and help us step up to be a global top-tier biotechnology company for immuno-oncology and neurodegenerative disease treatment."

"We are excited about this exclusive partnership, our first in South Korea. WuXi Biologics has been well recognized as a global leader in the development and manufacturing of difficult biologics such as bispecific antibodies. This agreement continues to exemplify our technical strength and unparalleled capacity in global biologics development and manufacturing," said Dr. Chris Chen, Chief Executive Officer of WuXi Biologics. "We are able to initiate 60 IND-enabling programs and 3 BLA-enabling programs per year, enabled by one of the largest biologics development teams in the industry of approximately 2000 scientists. With globally recognized technical capabilities and unparalleled capacities, we are transforming how biologics are developed in the global setting."