October 11, 2017 Astellas Pharma Inc. (TSE: 4503, President and CEO: Yoshihiko Hatanaka, “Astellas”) reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the development of gilteritinib for adult patients with FLT3 mutation-positive (FLT3+) relapsed or refractory acute myeloid leukemia (AML) (Press release, Astellas, OCT 10, 2017, View Source [SID1234520835]). Fast Track designation is designed to facilitate the development, and expedite the FDA review, of drugs to treat serious and life-threatening conditions so that, if approved, the compounds can reach the market expeditiously.

“Mutations of FLT3 in AML are associated with a poor prognosis and we are committed to working with the FDA to meet the requirements of the expedited review process,” said Steven Benner, M.D., senior vice president and global therapeutic area head, oncology development, Astellas. “We are pleased that the FDA has acknowledged the urgent need for new therapies for FLT3+ AML patients, which may allow for an expedited review process for gilteritinib.”

Fast Track designation for gilteritinib may allow for more frequent meetings and correspondence with the FDA, consideration for Priority Review if supported by clinical data, and Rolling Review, which means Astellas can submit completed sections of its New Drug Application (NDA) for review by the FDA rather than waiting until every section of the application is completed before the NDA can be reviewed.

AML is a cancer that impacts the blood and bone marrow and is most commonly experienced in older adults. According to the American Cancer Society, in 2016 there were approximately 21,000 new patients diagnosed with AML in the United States and about 10,000 cases resulted in death.

Gilteritinib is an investigational compound that has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) as well as FLT3 tyrosine kinase domain (TKD), two common types of FLT3 mutations that are seen in approximately one-third of patients with AML. Further, gilteritinib has also demonstrated inhibition of AXL, which is reported to be associated with therapeutic resistance.

Astellas is currently investigating gilteritinib in various AML patient populations through four ongoing Phase 3 trials, including the registrational ADMIRAL trial in relapsed/refractory FLT3+ AML.

The safety and efficacy of the agent discussed herein are under investigation and have not been established. There is no guarantee that the agent will receive regulatory approval and become commercially available for the uses being investigated. Information about pharmaceutical products (including products currently
in development) which is included in this press release are not intended to constitute an advertisement or medical advice.

About Gilteritinib

Gilteritinib was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global rights to develop, manufacture and potentially commercialize gilteritinib. Astellas internally classifies highly prioritized research projects as “Fast Track,” meaning research and development time is minimized through the focused investment of both capabilities and resources. Gilteritinib was designated as our first Fast Track project.

On October 10, 2017 Seattle Genetics, Inc. (NASDAQ: SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Yoshihiko Hatanaka, “Astellas”) reported dosing of the first patient in EV-201, a registrational phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with checkpoint inhibitor (CPI) therapy (Press release, Seattle Genetics, OCT 10, 2017, View Source [SID1234520828]). The EV-201 study will assess the antitumor activity and safety of enfortumab vedotin to support potential registration under the U.S. Food and Drug Administration’s (FDA) accelerated approval regulations.

“Locally advanced or metastatic urothelial cancers are often aggressive and treatment-resistant. Treatment options are limited for those many patients who do not respond to chemotherapy and checkpoint inhibitors, or CPIs. In addition, there are no FDA-approved therapies for patients who progress following CPI treatment,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “Initiation of this pivotal phase 2 trial of enfortumab vedotin is a significant advance toward our goal of providing a new treatment option for locally advanced or metastatic urothelial cancer.”

The primary endpoint of the single-arm, open-label trial is confirmed objective response rate (ORR), per independent review. Secondary endpoints include assessments of overall survival, progression free-survival, safety and tolerability. The study will enroll approximately 120 patients at multiple centers globally, and enfortumab vedotin will be administered three of every four weeks for the duration of treatment.

“The initiation of the EV-201 clinical trial demonstrates our continued commitment to patients living with locally advanced or metastatic urothelial cancer,” said Steven Benner, M.D., Senior Vice President and Global Therapeutic Area Head, Oncology Development at Astellas. “Our decision to move forward with this registrational trial is based on the results of our ongoing Phase 1 study, and we look forward to future clinical development milestones for enfortumab vedotin.”

The companies also plan to initiate a combination trial of enfortumab vedotin with CPI therapy in late 2017.

For more information about the phase 2 pivotal trial, including enrolling centers, please visit www.clinicaltrials.gov.

About Urothelial Cancer

Urothelial cancer is most commonly found in the bladder (90 percent). According to the American Cancer Society, approximately 79,000 people in the U.S. will be diagnosed with bladder cancer during 2017 and almost 17,000 will die from the disease. Outcomes are poor for patients diagnosed with metastatic disease, with a five-year survival rate of five percent.

About Enfortumab Vedotin

Enfortumab vedotin is an investigational ADC composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent, MMAE, using Seattle Genetics’ proprietary, industry-leading linker technology. Enfortumab vedotin targets Nectin-4, a cell adhesion molecule identified as an ADC target by Agensys (an affiliate of Astellas), which is expressed on many solid tumors.

Nectin-4 is highly expressed in urothelial cancers, particularly in bladder cancer. Preclinical data demonstrate that enfortumab vedotin binds to Nectin-4 on cancer cells and releases the cell-killing agent into these target cells upon internalization.

On October 10, 2017 OncoSec Medical Incorporated (“OncoSec” or the “Company”) (NASDAQ:ONCS), a company developing intratumoral cancer immunotherapies, reported that it has initiated its phase 2b registration directed trial, PISCES/KEYNOTE-695 (Press release, OncoSec Medical, OCT 10, 2017, View Source [SID1234520827]). The PISCES/KEYNOTE-695 study is a global, multicenter phase 2b trial of OncoSec’s investigational therapy, ImmunoPulse IL-12 (intratumoral pIL-12 [tavokinogene telseplasmid or “tavo”] with electroporation), combined with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy marketed by Merck (known as MSD outside the US and Canada), in patients with unresectable metastatic melanoma who have progressed or are progressing on an anti-PD-1 therapy.

“Patients with metastatic melanoma who are progressing or have progressed on anti-PD-1 therapy have limited treatment options. We believe the combination of ImmunoPulse IL-12 and pembrolizumab offers a potentially transformative approach for these patients given the absence of approved therapies,” said Punit Dhillon, CEO and President at OncoSec. “The advancement of the PISCES trial marks an important milestone for the Company.”

The phase 2b, Simon 2-stage multicenter study of intratumoral tavo with electroporation in combination with intravenous KEYTRUDA will enroll approximately 48 patients with histological diagnosis of melanoma with progressive locally advanced or metastatic disease defined as Stage III or Stage IV. The primary endpoint will be the Best Overall Response Rate (BORR).

“ImmunoPulse IL-12 and pembrolizumab are immunotherapies designed to modulate the patient’s own immune response to fight cancer,” said Sharron Gargosky Ph.D., Chief Clinical and Regulatory Officer at OncoSec. “We are pleased with the progress of the ongoing PISCES trial, which has benefitted from our clinical trial collaboration and supply agreement with Merck.”

The collaboration agreement, which was announced in May 2017, is between OncoSec Medical Incorporated and Merck, through a subsidiary. Under the agreement, OncoSec will sponsor and fund the study and Merck will provide KEYTRUDA.

To learn more about the trial, visit www.oncosec.com. Additional details can also be found at www.clinicaltrials.gov via NCT03132675.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

ImmunoPulse is a registered trademark of OncoSec Medical Incorporated, San Diego, CA, USA.

About Metastatic Melanoma1

Melanoma is a type of skin cancer that begins in skin cells called melanocytes. As the cancer progresses, melanoma becomes more difficult to treat once it spreads beyond the skin, such as the lymphatic system (metastatic disease). Given its occurrence young individuals, the potential years of life lost to melanoma can be higher when compared with other cancers. Although melanoma is a rare form of skin cancer, it accounts for over 75% of skin cancer deaths. The American Cancer Society estimates that approximately 87,000 new melanoma cases and 10,000 deaths from the disease will occur in the United States in 2017. Additionally, the World Health Organization estimates that approximately 132,000 new cases of melanoma are diagnosed around the world every year.

1 American Cancer Society (View Source); World Health Organization (View Source)

About PISCES (Anti-PD-1 IL-12 Stage III/IV Combination Electroporation Study)

PISCES is a global, multicenter phase 2b, open-label trial of intratumoral plasma encoded IL-12 (tavokinogene telseplasmid or “tavo”) delivered by electroporation in combination with intravenous pembrolizumab in patients with stage III/IV melanoma who have progressed or are progressing on either pembrolizumab or nivolumab treatment. The Simon 2-stage study of intratumoral tavo plus electroporation in combination with pembrolizumab will enroll approximately 48 patients with histological diagnosis of melanoma with progressive locally advanced or metastatic disease defined as Stage III or Stage IV. The primary endpoint will be the Best Overall Response Rate (BORR).

On October 10, 2017 RedHill Biopharma Ltd. (NASDAQ:RDHL) (Tel-Aviv Stock Exchange:RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company primarily focused on late clinical-stage development and commercialization of proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, reported that Mr. Adi Frish, RedHill’s Senior VP Business Development and Licensing, will present a corporate overview at the BioNetwork 2017 Partnering Summit, on Monday, October 23, 2017, at 12:20 pm PDT , at the Ritz-Carlton Hotel, Laguna Niguel, CA (Press release, RedHill Biopharma, OCT 10, 2017, View Source [SID1234520823]).

A copy of the presentation to be made by Mr. Frish will be available on the Company’s website and may be viewed at: View Source

On October 10, 2017 Genmab A/S (Nasdaq Copenhagen: GEN) and Seattle Genetics, Inc. (NASDAQ: SGEN) reported a decision to start a Phase II study of tisotumab vedotin in patients with recurrent and/or metastatic cervical cancer (Press release, Genmab, OCT 10, 2017, View Source [SID1234520822]). The study could provide the basis for a regulatory application for approval. Tisotumab vedotin consists of a tissue factor (TF)-targeted antibody linked to the cell-killing agent monomethyl auristatin E (MMAE). TF is a protein expressed on a broad range of solid tumors. The Phase II trial is single arm and includes about 100 patients with recurrent or metastatic cervical cancer who relapsed or progressed after standard of care treatment. The companies plan to start enrolling patients by the first half of 2018.

“We are very pleased to see the clinical development of tisotumab vedotin progress in patients with cervical cancer — an area with a strong unmet medical need. The study provides an opportunity for accelerated registration. We look forward to the continuing development of this promising first-in-class antibody-drug conjugate,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

“Standard therapies for previously treated recurrent and/or metastatic cervical cancer generally result in response rates of less than 15 percent and a median overall survival of six to eight months,” said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “Based on promising data from the Phase I/II clinical trial of tisotumab vedotin in recurrent and/or metastatic cervical cancer and feedback from the Food and Drug Administration (FDA) on the planned trial, we and Genmab are advancing the program into a potentially registrational study for these patients with high unmet medical need.”

About the Phase II study

The single arm, multicenter Phase II study (GCT1015-04) of tisotumab vedotin monotherapy is expected to enroll about 100 patients with recurrent or metastatic cervical cancer who have experienced disease progression on or after platinum containing chemotherapy and who have received or are ineligible for bevacizumab. The primary endpoint of the study is overall response rate (ORR) as assessed by independent review of RECIST v1.1 criteria. The main secondary endpoints are duration of response (DoR) and safety.

About Cervical Cancer

Cervical cancer originates in the cells lining the cervix, which connects the uterus to the birth canal. About 13,000 women are expected to be diagnosed with cervical cancer in the US in 2017, with an estimated 4000 deaths.1 Globally, it was estimated that 527,000 people would be diagnosed and 265,000 would die from the disease in 2012, the vast majority of these patients being in the developing world.2 Routine medical examinations and the human papillomavirus (HPV) vaccine have had a positive impact on the incidence of cervical cancer in the developed world. Despite these advances, women are still diagnosed with cervical cancer, which can have a devastating impact, particularly in the recurrent or metastatic setting. Standard therapies for previously treated recurrent/metastatic cervical cancer generally result in response rates of less than 15 percent and a median overall survival of 6 to 8 months.3-10

About Tisotumab Vedotin

Tisotumab vedotin is an antibody-drug conjugate (ADC) composed of Genmab’s human antibody that binds to tissue factor (TF) and Seattle Genetics’ ADC technology that utilizes a cleavable linker and the cytotoxic drug monomethyl auristatin E (MMAE). TF is a protein involved in tumor signaling and angiogenesis. Based on its high expression on many solid tumors and its rapid internalization, TF was selected as a target for an ADC approach. Tisotumab vedotin is being evaluated in ongoing Phase I/II clinical studies for solid tumors and a Phase II trial in recurrent and/or metastatic cervical cancer is planned to start by the first half of 2018. Tisotumab vedotin is being co-developed by Genmab and Seattle Genetics, under an agreement in which the companies share all future costs and profits for the product on a 50:50 basis.