On February 22, 2016 Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a clinical stage biopharmaceutical company focused on discovering and developing novel cellular immunotherapies for cancers and orphan inherited blood disorders, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for BPX-501, the Company’s lead product candidate (Press release, Bellicum Pharmaceuticals, FEB 22, 2016, View Source [SID:1234509128]).

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The FDA designation is for the combination of BPX-501 genetically modified T cells and activator agent rimiducid as "replacement T-cell therapy for the treatment of immunodeficiency and graft versus host disease (GvHD) after allogeneic hematopoietic stem cell transplant." BPX-501 is an adjunct T-cell therapy incorporating the Company’s proprietary CaspaCIDe safety switch.

Following an allogeneic transplant, a lack of sufficient mature T cells constitutes immune deficiency that can contribute to infections, viral reactivation, and relapse. The ability to correct this immune deficiency through the add-back of mature donor T cells, without raising the risk of uncontrollable GvHD, has the potential to fundamentally change the risk profile of allogeneic transplantation.

"Expanding the availability of hematopoietic stem cell transplants to more patients with rare genetic diseases and blood cancers is a primary goal of our BPX-501 program," commented Tom Farrell, President and CEO of Bellicum Pharmaceuticals. "The FDA’s approval of our request for orphan drug designation is an important milestone that supports our efforts to address key risks and improve outcomes in allogeneic transplant which could make the procedure more viable for patients who lack a perfect match donor."

BPX-501 is currently being evaluated in multiple Phase 1/2 clinical trials in adults and pediatric patients with leukemias, lymphomas, and genetic blood diseases in the U.S. and Europe. Interim results presented at the 2015 ASH (Free ASH Whitepaper) Annual Meeting in pediatric patients with a variety of genetic diseases, including beta thalassemia, Wiskott-Aldrich and SCID, demonstrated disease-free outcomes following a haploidentical, T cell-depleted hematopoietic stem cell transplant, followed by an add-back of BPX-501 donor T cells. Results demonstrated reduced infection rates, faster immune reconstitution, and reductions in time to hospital discharge and in re-hospitalizations, compared to historical controls.

About Orphan Drug Designation

The FDA’s Office of Orphan Products Development (OOPD) provides orphan designation to drugs and biologics which are intended for the safe and effective treatment, diagnosis or prevention of rare diseases and disorders that affect fewer than 200,000 people in the U.S. Orphan designation also qualifies a company for various development incentives, including tax credits for qualified clinical testing and marketing exclusivity for a period of seven years.

About BPX-501

BPX-501 is an adjunct T cell therapy of genetically modified donor T cells incorporating Bellicum’s proprietary CaspaCIDe safety switch. The product candidate is designed to provide a safety net to eliminate the BPX-501 alloreactive T cells should severe GvHD occur, enabling physicians to more safely perform haploidentical stem cell transplants by adding back the BPX-501 genetically engineered T cells to speed immune reconstitution and provide control over viral infections.

On February 22, 2016 Seattle Genetics, Inc. (Nasdaq: SGEN) reported the initiation of a phase 1/2 clinical trial of vadastuximab talirine (SGN-CD33A; 33A) in combination with azacitidine (Vidaza) in patients with previously untreated myelodysplastic syndrome (MDS) (Press release, Seattle Genetics, FEB 22, 2016, View Source [SID:1234509127]).

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33A is an antibody-drug conjugate (ADC) targeted to CD33 utilizing Seattle Genetics’ newest technology, comprising an engineered cysteine antibody (EC-mAb) stably linked to a highly potent DNA binding agent called a pyrrolobenzodiazepine (PBD) dimer. Azacitidine is a hypomethylating agent (HMA) commonly used in the treatment of MDS. MDS is known to be a precursor to acute myeloid leukemia (AML), and broadly expresses CD33.

"Most newly diagnosed patients with intermediate or high risk MDS are ineligible for allogeneic stem cell transplant due to age, comorbidities or lack of appropriate donor. For these patients, novel therapies are urgently needed to prolong survival and delay disease progression into AML," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "In our phase 1 AML clinical trial evaluating 33A plus HMAs (azacitidine or decitabine), we have observed encouraging tolerability and depletion of blasts from the bone marrow in many patients, and we recently presented preclinical data demonstrating synergistic activity of 33A plus HMAs. Expanding our clinical evaluation of 33A in MDS is part of a broad clinical development strategy to establish 33A as the foundation of care for patients with myeloid malignancies."

The phase 1/2, open-label, multi-center clinical trial is designed to evaluate the safety and activity of 33A administered in combination with azacitidine in patients with previously untreated International Prognostic Scoring System (IPSS) Intermediate-2 or high risk MDS. Phase 1 of the study will identify the recommended dose of 33A when combined with azacitidine in this patient population. The phase 2 portion of the trial will be a randomized, double-blind, placebo-controlled study evaluating azacitidine with or without 33A.

The primary endpoint in phase 1 is determination of the recommended 33A dose in combination with azacitidine. The primary endpoint in phase 2 is to compare the overall response rate between the two treatment arms. The secondary endpoints include evaluation of safety, best response, duration of response, progression-free survival and overall survival. The phase 1/2 trial will enroll approximately 130 patients at approximately 35 centers in North America.

In addition to this MDS trial, Seattle Genetics is evaluating 33A broadly across multiple lines of therapy in patients with AML, including the following ongoing trials:

A phase 1 trial of 33A monotherapy and in combination with HMAs in AML patients who have relapsed/declined intensive frontline therapy or are newly diagnosed;
A phase 1b trial in combination with standard of care intensive chemotherapy, including cytarabine and daunorubicin, for younger fit patients with AML; and,
A phase 1/2 trial in patients with relapsed or refractory AML evaluating 33A monotherapy as a pre-conditioning regimen prior to an allogeneic stem cell transplant and also for use as maintenance therapy following transplant.
Additionally, a phase 3 clinical trial to evaluate 33A in combination with HMAs in previously untreated older AML patients is planned to begin by the third quarter of 2016.

More information about SGN-CD33A and ongoing clinical trials can be found at www.ADC-CD33.com.

With more than 15 years of experience and innovation, Seattle Genetics is the leader in developing ADCs. ADCs are monoclonal antibodies that are designed to selectively deliver cell-killing agents to tumor cells. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing antitumor activity.

For more information about the trial, including enrolling centers, please visit www.clinicaltrials.gov.

About Myelodysplastic Syndrome

Myelodysplastic Syndromes (MDS) are a group of diverse bone marrow disorders in which the bone marrow does not produce enough healthy blood cells. MDS is often referred to as a "bone marrow failure disorder". MDS is a disorder that starts when abnormal progenitor cells in the bone marrow are damaged and have problems making new blood cells. Blood cells formed by the abnormal bone marrow cells are defective. Defective cells often have reduced survival and function, resulting in low blood counts and abnormal behavior. In advanced MDS, blasts are detectable in the bone marrow and usually express CD33. In about one-third of patients, MDS can progress to a rapidly growing cancer of the bone marrow cells called acute myeloid leukemia, or AML. According to the American Cancer Society, in 2016 more than 19,500 new cases of MDS will be diagnosed and more than 10,000 deaths will occur from MDS.

About Vadastuximab Talirine (SGN-CD33A)

Vadastuximab talirine (SGN-CD33A; 33A) is a novel ADC targeted to CD33 utilizing Seattle Genetics’ newest ADC technology. CD33 is expressed on most AML and MDS blast cells. The CD33 antibody is attached to a highly potent DNA binding agent, a pyrrolobenzodiazepine (PBD) dimer, via a proprietary site-specific conjugation technology to a monoclonal antibody with engineered cysteines (EC-mAb). PBD dimers are significantly more potent than systemic chemotherapeutic drugs and the site-specific conjugation technology (EC-mAb) allows uniform drug-loading of the cell-killing PBD agent to the anti-CD33 antibody. The ADC is designed to be stable in the bloodstream and to release its potent DNA binding agent upon internalization into CD33-expressing cells. 33A is being evaluated in ongoing phase 1 and phase 1/2 clinical trials in AML and MDS and a planned pivotal phase 3 clinical trial for patients with AML.

On February 22, 2016 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported a strategic research collaboration with TESARO and Merck, known as MSD outside the U.S. and Canada, to help identify potential responders to an investigational combination drug therapy using TESARO’s PARP inhibitor (niraparib) plus KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy (Press release, Myriad Genetics, FEB 22, 2016, View Source [SID:1234509126]).

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Under the terms of the agreement, the companies will use Myriad’s myChoice HRD test and new tumor tests to evaluate treatment response in a clinical trial evaluating the combination of niraparib plus pembrolizumab in patients with triple negative breast cancer (TNBC) or ovarian cancer. Other terms of the deal were not disclosed.

"The combination of a PARP inhibitor and anti-PD-1 antibody may offer a novel way to treat women with triple negative breast cancer or ovarian cancer," said Mary Lynne Hedley, Ph.D., president and COO of TESARO. "Our goal is to use Myriad’s assays to help enrich for those patients who will respond to the treatment and have the best chance for success."

"Treatment options for patients with triple negative breast cancer are extremely limited," said Jerry Lanchbury, Ph.D., chief scientific officer, Myriad Genetics, Inc. "We are very excited to expand our collaboration with TESARO and Merck to determine if our novel companion diagnostic assays can optimize the potential for this experimental combination therapy."

The new agreement builds upon a collaboration with TESARO that began in March 2014. Since then, Myriad has been working with TESARO to use the myChoice HRD test to identify ovarian cancer patients who may respond to niraparib, which is in Phase 3 clinical development.

About myChoice HRD

Myriad’s myChoice HRD is the first homologous recombination deficiency test that can detect when a tumor has lost the ability to repair double-stranded DNA breaks, resulting in increased susceptibility to DNA-damaging drugs such as platinum drugs or PARP inhibitors. High myChoice HRD scores reflective of DNA repair deficiencies are prevalent in all breast cancer subtypes, ovarian and most other major cancers. In previously published data, Myriad showed that the myChoice HRD test predicted drug response to platinum therapy in certain patients with triple negative breast and ovarian cancers. It is estimated that 1.8 million people in the United States and Europe who are diagnosed with cancers annually may be candidates for treatment with DNA-damaging agents.

On February 22, 2016 AVEO Oncology (NASDAQ:AVEO) reported that a registration dossier seeking to obtain marketing authorization of tivozanib as a first line treatment of advanced renal cell carcinoma ("RCC") has been accepted by the Ministry of Health ("MoH") of the Russian Federation (Press release, AVEO, FEB 22, 2016, View Source [SID:1234509125]). The dossier was submitted in December 2015 by Pharmstandard Group, the largest Russian pharmaceutical group ("Pharmstandard").

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In August 2015, AVEO licensed Pharmstandard rights to the development, manufacture and commercialization of tivozanib in the territories of Russia, Ukraine and the Commonwealth of Independent States (CIS), for all indications other than non-oncologic diseases or conditions of the eye.

Marketing authorization is being sought by Pharmstandard based upon results from TIVO-1, AVEO’s global, randomized, controlled Phase 3 trial evaluating tivozanib compared to sorafenib in patients with advanced RCC. AVEO is eligible to receive $7.5 million in connection with the first marketing authorization of tivozanib in Russia, provided that Russian regulatory authorities grant marketing approval based on the results from TIVO-1. If Russian regulatory authorities require additional studies to be performed prior to approval, the amount potentially payable to AVEO upon approval would be $3.0 million. AVEO is also eligible to receive a high single-digit royalty on net sales, if any, in the above mentioned territories. A percentage of any milestone and royalty payments received by AVEO are due to Kyowa Hakko Kirin as a sublicensing fee.

"Acceptance of a registration dossier marks an important step toward potential approval of tivozanib in RCC in territories outside the United States," said Michael Bailey, president and chief executive officer of AVEO. "We look forward to MoH review of the dossier as we work toward submitting a marketing authorization application to the European Medicines Agency with our partner EUSA Pharma. In parallel, we continue to work toward the potential initiation of a Phase 3 trial of tivozanib in third line RCC to potentially enable registration in the first- and third-lines in the U.S., as well as the potential initiation of a combination study with a checkpoint inhibitor. Both studies may provide important strategic datasets in a rapidly evolving treatment landscape in RCC."

About Tivozanib

Tivozanib is an oral, once-daily, investigational vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI). It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications. Tivozanib has been evaluated in several tumors types, including renal cell, colorectal and breast cancers.