On April 13, 2017 Celsion Corporation (NASDAQ:CLSN) reported publication of the article, "Lyso-Thermosensitive Liposomal Doxorubicin for Treatment of Bladder Cancer," in the International Journal of Hyperthermia (Press release, Celsion, APR 13, 2017, View Source [SID1234518537]). The article describes the results of porcine in vivo studies to evaluate ThermoDox in combination with loco-regional mild hyperthermia for targeted drug delivery to the bladder wall as a potential treatment for bladder cancer. Swine bladder walls are similar in proportion and composition to human bladders. Doxorubicin accumulation and distribution within the bladder wall with ThermoDox plus mild bladder hyperthermia was achieved at concentrations nearly ten times higher than with free intravenous doxorubicin combined with mild bladder hyperthermia. The study was conducted under a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health (NIH) to evaluate whether ThermoDox combined with mild heating of the bladder can target drug delivery in the bladder.

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

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

                  Schedule Your 30 min Free Demo!

It is estimated that over 79,000 new cases of urinary bladder cancer will be diagnosed in the United States in 2017 and over 16,800 people will die of the disease during this same period. Approximately 70 percent of new cases of bladder cancer present with non-muscle invasive disease and are typically treated by a technique called transurethral resection of the bladder which removes as much of the tumor as possible. However, 40 percent of patients with high risk non-muscle invasive disease experience a recurrence and another 33 percent experience disease progression. To reduce this high rate of recurrence, intravesical (in the bladder) therapy is used. Intravenous administration of free doxorubicin is commonly used as part of an effective standard perioperative chemotherapy regimen for muscle invasive disease; however results with intravesical doxorubicin have been less effective presumably from inability to deliver doxorubicin across the bladder urothelium (epithelial surface of the bladder).
The NIH studies were conducted under the direction of Dr. Bradford Wood, MD, Director, NIH Center for Interventional Oncology and Chief, NIH Clinical Center Interventional Radiology. The results of the studies are summarized below:
• Range of doxorubicin concentrations from the urothelium to the serosa (outer surface of the bladder):
20.32 – 3.52 ug/g for ThermoDox + hyperthermia (HT)
2.34 – 0.61 ug/g for free doxorubicin + hyperthermia
2.18 – 0.51 ug/g for ThermoDox with no hyperthermia
• Average doxorubicin concentrations in the urothelium/lamina:
9.7 +/- 0.67 ug/g for ThermoDox + hyperthermia (HT)
1.2 +/- 0.39 ug/g for free doxorubicin + hyperthermia
1.15 +/- 0.38 ug/g for ThermoDox with no hyperthermia
• Average doxorubicin concentrations in the muscularis:
4.09 +/- 0.81 ug/g for ThermoDox + hyperthermia (HT)
0.86 +/- 0.24 ug/g for free doxorubicin + hyperthermia
0.62 +/- 0.15 ug/g for ThermoDox with no hyperthermia
Computational model results were similar to the measured doxorubicin levels and suggest that adequate temperatures were reached within the bladder for drug release from the lyso-thermosensitive liposomal doxorubicin,
ThermoDox.

"The incomplete response of bladder tumors to intravesical drugs, like doxorubicin and mitomycin C, has been attributed in part to inadequate drug delivery and poor penetration across the urothelium resulting in sub-therapeutic drug concentrations in the bladder wall," said Dr. Bradford Wood, MD, Director, NIH Center for Interventional Oncology and Chief, NIH Clinical Center Interventional Radiology. "To address this limitation, one promising strategy to enhance the permeability of the bladder wall to improve the efficacy of intravesical chemotherapy is the use of hyperthermia to stimulate the release of chemotherapeutic agents from thermosensitive nanocarriers for patients who have failed standard first line therapy for bladder cancer."

"The NIH’s continued research interest in ThermoDox and its application in the treatment of many difficult to treat cancers underscores the significance of ThermoDox’s potential and its unique means of locally concentrating doxorubicin in a highly effective way," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "This study not only reinforces ThermoDox’s mechanism, it provides further assurance that the conclusions from the NIH’s independent analysis of ThermoDox plus radio frequency ablation for the treatment of primary liver cancer are based on a broad set of clinical and preclinical evidence. The data presented by the NIH at the 2016 RSNA Annual Meeting in November 2016 showed that the longer the target tissue is heated, the greater is the clinical benefit. Multiple experiments conducted by Celsion suggest that this is the result of increased doxorubicin tissue concentration, and we believe provides strong validation for our ongoing global Phase III OPTIMA Study in primary liver cancer. A successful OPTIMA Study will provide the means to expand ThermoDox’s utility for patients with bladder cancer."

About ThermoDox
Celsion’s most advanced program is a heat-mediated, tumor-targeting drug delivery technology that employs a novel heat-sensitive liposome engineered to address a broad range of difficult-to-treat cancers. The first application of this platform is ThermoDox, a lyso-thermosensitive liposomal doxorubicin (LTLD), whose novel mechanism of action delivers high concentrations of doxorubicin to a region targeted with the application of localized heat at 40°C, just above body temperature. ThermoDox has the potential to address a broad range of cancers.

Celsion’s LTLD technology leverages two mechanisms of tumor biology to deliver higher concentrations of drug directly to the tumor site. In the first mechanism, rapidly growing tumors have leaky vasculature, which is permeable to liposomes and enables their accumulation within tumors. Leaky vasculature influences a number of factors within the tumor, including the access of therapeutic agents to tumor cells. Administered intravenously, ThermoDox is engineered with a half-life to allow significant accumulation of liposomes at the tumor site as these liposomes recirculate in the blood stream. In the second mechanism, when an external heating device heats tumor tissue to a temperature of 40°C or greater, the heat-sensitive liposome rapidly changes structure and the liposomal membrane selectively dissolves, creating openings that can release a chemotherapeutic agent directly into the tumor and into the surrounding vasculature. Drug concentration increases as a function of the accumulation of liposomes at the tumor site, but only where the heat is present. This method damages only the tumor and the area related to tumor invasion, supporting more precise drug targeting.

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.

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

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

                  Schedule Your 30 min Free Demo!

"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.

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.

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

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

                  Schedule Your 30 min Free Demo!

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."

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]).

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

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

                  Schedule Your 30 min Free Demo!

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.

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.

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

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

                  Schedule Your 30 min Free Demo!

"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.