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AVEO Announces Submission of Response to Tivozanib Marketing Authorization Application Day 180 List of Outstanding Issues

On April 13, 2017 AVEO Oncology (NASDAQ: AVEO) reported that its European licensee for tivozanib, EUSA Pharma, has submitted responses to the European Medicines Agency (EMA) Day 180 List of Outstanding Issues (LOI) related to the Marketing Authorization Application (MAA) for tivozanib as a first-line treatment for renal cell carcinoma (Press release, AVEO, APR 13, 2017, View Source [SID1234518533]). With submission of the response complete, EUSA remains tentatively scheduled to provide an oral explanation to the EMA’s Committee for Medicinal Products for Human Use (CHMP) at its May 2017 meeting.

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"Responding to the Day 180 List of Outstanding Issues is another important step in the tivozanib MAA, and we continue to work with EUSA Pharma in their effort to seek regulatory approval for tivozanib in Europe," said Michael Bailey, president and chief executive officer of AVEO. "This includes supporting EUSA as they proceed toward a planned oral explanation to the CHMP in May, while at the same time we continue to advance our registration strategy for tivozanib in the United States. We look forward to providing updates on these dual paths as we complete the final phase of the European approval process and work toward our goal of full enrollment in our U.S. registration-directed TIVO-3 study."

As previously announced, the Day 180 LOI signified that the MAA is not approvable at that time, and outlines outstanding deficiencies, which are then required to be satisfactorily addressed in an oral explanation and/or in writing prior to a final application decision.

About Tivozanib

Tivozanib is an oral, once-daily, 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 investigated in several tumors types, including renal cell, colorectal and breast cancers.

FDA allows NuvOx Pharma to run a Phase II Clinical Trial in Brain Cancer

On April 12, 2017 Nuvox Pharma reported that the FDA has allowed an Investigational New Drug (IND) application to initiate a Phase II clinical trial for its oxygen therapeutic, NVX-108, in patients with the hypoxic solid brain tumor, glioblastoma multiforme (GBM) (Press release, NuvOx Pharma, APR 12, 2017, View Source [SID1234518539]). NVX-108 is an injectable drug that travels through the bloodstream arriving first at the lungs to pick up oxygen and finally to hypoxic tissue where it passively delivers the oxygen. It is designed to reduce tumor hypoxia in order to make tumors more sensitive to radiation therapy and chemotherapy.

The clinical trial’s principal investigator, Baldassarre Stea, MD, PhD, said, "Tumor hypoxia is known to be a problem in many tumor types, including GBM. Hypoxic tumors are resistant to radiation therapy and certain kinds of chemotherapy. By increasing tumor oxygen levels, NVX-108 is designed to improve the effectiveness of these therapies in order to kill cancer cells more effectively and increase patient survival. Clinical trials are needed to see if NVX-108 can become approved by regulators."

Caligor to Support Puma Biotechnology’s Expanded Access Program for PB272 (Neratinib) in the United States

On April 12, 2017 Caligor Opco LLC, which specializes in early access to medicines and drug life-cycle management, reported that it will provide regulatory and logistical management for Puma Biotechnology’s (Nasdaq: PBYI) expanded access program (EAP) for its investigational breast cancer therapy, PB272 (neratinib), in the United States (Press release, Caligor Opco, APR 12, 2017, View Source [SID1234518531]).

The U.S. Food and Drug Administration (FDA) permits expanded access to investigational drugs for treatment use for patients with serious or immediately life-threatening diseases or conditions who do not otherwise qualify for participation in a clinical trial and lack satisfactory therapeutic alternatives.

The EAP will provide access to neratinib for the treatment of early stage HER2-positive breast cancer (extended adjuvant setting), HER2-positive metastatic breast cancer and HER2-mutated solid tumors. Patients must not be able to participate in any ongoing neratinib clinical trial to qualify for the EAP. Caligor also is providing regulatory, logistical, and supply chain support for Puma’s Managed Access Program for neratinib outside the United States.

"We are gratified by the trust and confidence Puma has placed in us," said Tammy Bishop, Caligor’s Chief Commercial Officer. "Within the past year, the FDA has introduced a streamlined application process and new guidance designed to improve its expanded access programs, and those initiatives have been extremely positive. We look forward to working with regulators and physicians to facilitate access to neratinib for patients who may benefit from this therapy."

About the Neratinib Expanded Access Program

The neratinib EAP is a program for U.S. patients with early stage HER2-positive breast cancer (extended adjuvant setting), HER2-positive metastatic breast cancer and HER2-mutated solid tumors. This EAP is being administered on behalf of Puma by Caligor Opco. U.S. healthcare professionals seeking more information about the neratinib EAP can email [email protected] for additional information. Patients who are interested in enrolling in the neratinib EAP should speak with their physician to determine if neratinib is an appropriate option. Neratinib is an investigational agent and, as such, has not been approved by the FDA or any other regulatory agencies in any markets.

argenx launches Phase II study of ARGX-110 as a monotherapy in relapsed/refractory CTCL patients

On April 12, 2017 argenx (Euronext Brussels: ARGX), a clinical-stage biotechnology company developing a deep pipeline of differentiated antibody-based therapies for the treatment of severe autoimmune diseases and cancer, reported the initiation of a Phase II trial of ARGX-110 as a monotherapy in patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL) (Press release, arGEN-X, APR 12, 2017, View Source [SID1234518530]). ARGX-110 is the Company’s SIMPLE Antibody targeting CD70.

"We have previously observed evidence of biological activity and a promising safety profile in several CD70-positive CTCL patients treated in an ongoing Phase I safety-expansion cohort, resulting in several patients with partial response or stable disease. Based on these preliminary results, we opted to further evaluate ARGX-110 as a monotherapy in an exploratory Phase II study to demonstrate the intrinsic activity of the drug in relapsed/refractory CTCL patients and to broaden our efficacy database," commented Nicolas Leupin, CMO of argenx. "This marks the second Phase 1/2 study of ARGX-110 with the first having launched in December 2016 as a combination therapy with standard of care in AML."

The Phase II clinical trial will enroll up to 10 additional relapsed/refractory CTCL patients, and will be conducted at multiple centers in Europe. The primary endpoints of the trial are safety and efficacy and secondary endpoints include pharmacokinetics and immunogenicity. Interim data are expected by the end of 2017, and we expect to report topline data in the second half of 2018.

ARGX-110 is also being studied as a combination therapy with standard of care azacitidine in newly diagnosed, elderly acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) patients.

About ARGX-110

ARGX-110 is a SIMPLE Antibody targeting CD70, an immune checkpoint target involved in hematological malignancies, several solid tumors and severe autoimmune diseases. ARGX-110 works in three ways: i) blocks growth of tumor cells, ii) kills cancer cells and iii) restores immune surveillance against tumors (Silence K. et al. mAbs 2014; 6 (2):523-532). ARGX-110 is currently being evaluated in a Phase II combination trial in patients with newly diagnosed acute myeloid leukaemia (AML) and high-risk myelodysplastic syndrome and a Phase II trial in patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL). Preclinical work on ARGX-110 in AML was done in collaboration with the Tumor Immunology Lab of Prof. A. F. Ochsenbein at the University of Bern, who won together with Prof Manz from the University Hospital of Zürich, the prestigious 2016 Otto Naegeli Prize for his breakthrough research on CD70/CD27 signaling with therapeutic potential for cancer patients.

About CTCL

Lymphoma is the most common type of blood cancer. TCL accounts for 6% of all cases of lymphoma and can be divided into subtypes such as peripheral TCL (PTCL), angioimmunoblastic TCL (AITL), anaplastic large cell lymphoma (ALCL), and CTCL. According to the Cutaneous Lymphoma Foundation, the incidence of CTCL in the United States is approximately 3,000 new cases per year. The two most common types of CTCL are mycosis fungoides, representing approximately 50% of CTCL patients, and a more advanced form known as Sezary syndrome, representing approximately 15% of CTCL patients. In both mycosis fungoides and Sezary syndrome, visible skin lesions offer an ongoing means with which to monitor both the progression of disease and the impact of treatment. Sezary syndrome is distinguished by the presence of malignant lymphocytes in the blood, an extensive rash covering over 80% of the body and tumors visible on the skin.

Kancera provides an operational update of the PFKFB3 project

On April 12, 2017 Kancera reported that PFKFB3-inhibitor KAN0438757 increases the effect of a promising class of drugs for intractable cancer (Press release, Kancera, APR 12, 2017, View Source [SID1234518529]). Kancera has strengthened their development of drugs directed against PFKFB3 and DNA repair through a new recruitment. The European and US patent authorities have announced that a patent will be granted for the PFKFB- inhibitor KAN0438757 and analogues of this substance.

Kancera, together with the Thomas Helleday group at the Science for Life laboratory, have previously shown that Kancera’s PFKFB3 inhibitor increases the effect of DNA-damaging treatment such as chemotherapy and radiation by antagonizing cell repair functions. This treatment concept has grown strongly with the demonstration that PARP inhibitors, which act by this type of mechanism, have proven successful in the treatment of ovarian cancer, breast cancer and castration-resistant prostate cancer.

PARP-inhibitors, such as Veliparib, are effective against cancers that are defective in their ability to repair DNA (recombination-defective), while cancer that retains this ability resists the same treatment.

Studies now show that cancer cells that are resistant to Veliparib become sensitive to treatment when Veliparib is combined with KAN0438757. This means that Kancera’s PFKFB3 inhibitor in combination with PARP inhibitors can combat more treatment-recalcitrant cancers than PARP inhibitors alone. The reason Kancera PFKFB3 inhibitors increase the effect of Veliparib is that they block cancer cells’ ability to repair DNA.

Since normal, healthy cells are neither recombination-defective nor do they depend on PFKFB3 for their DNA repair function, it is possible that such a combination could be well tolerated with few side effects.

Kancera AB (publ) has employed Nina Gustafsson PhD as expert in the biology of DNA repair. Nina will divide her time between Kancera and Thomas Helleday’s Laboratory at the Karolinska Institute, with main responsibility in the latter as project and team leader. Nina holds a PhD from the Karolinska Institute of Medical Sciences and has received numerous research grants for her work on cancer metabolism and its relationship to DNA repair.

"With the recruitment of Nina Gustafsson we strengthen both Kancera’s expertise in DNA repair and our successful collaboration with the Karolinska Institute on the PFKFB3 project," says Thomas Olin, CEO of Kancera.

Kancera has received advance notice from the patent authorities in the EU and the United States that claimed around PFKFB3 inhibitor KAN0438757 will be granted.

About the PFKFB3 project
The project aims to develop inhibitors of the enzyme PFKFB3 so as to strangle cancer cell energy metabolism and thus render them vulnerable to chemotherapy and radiotherapy. Kancera AB has, together with Professor Thomas Helleday and his research group at Karolinska Institutet, made a surprising discovery that shows how the company inhibitor of PFKFB3 enters the cancer cell’s nucleus and enhances the effects of a newly given dose of radiation.