On June 13, 2018 Seattle Genetics, Inc. (Nasdaq:SGEN) reported dosing of the first patient in the phase 2 innovaTV 204 clinical trial evaluating the efficacy, safety and tolerability of tisotumab vedotin as monotherapy for patients with recurrent and/or metastatic cervical cancer who have relapsed or progressed after standard of care treatment (Press release, Seattle Genetics, JUN 13, 2018, View Source;p=RssLanding&cat=news&id=2354368 [SID1234527298]). Tisotumab vedotin is being developed in collaboration with Genmab A/S. The innovaTV 204 trial is intended to support potential registration under the U.S. Food and Drug Administration’s (FDA) accelerated approval regulations. Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) designed to target Tissue Factor antigen on cancer cell surfaces and deliver the cell-killing agent monomethyl auristatin E (MMAE) directly inside cancer cells. The Tissue Factor antigen target is overexpressed in the vast majority of patients with cervical cancer and in many other solid tumors, including ovarian, lung, pancreatic, colorectal and head and neck.

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"While significant advances have been made in the treatment and prevention of cervical cancer, there remains a need for targeted agents that are effective for patients who progress or relapse after standard treatments," said Robert Coleman, M.D., FACOG, FACS, Professor of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX and principal investigator of the innovaTV 204 trial. "In a prior study, tisotumab vedotin demonstrated encouraging results in previously treated recurrent and/or metastatic cervical cancer, an area of unmet need where there is no established standard of care and response rates are limited."

"With the initiation of this phase 2 study of tisotumab vedotin for women with previously treated recurrent and/or metastatic cervical cancer, we now have four late-stage development programs on registrational pathways to achieve our goal of becoming a global, multi-product oncology company," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "In addition, we plan to evaluate tisotumab vedotin in collaboration with Genmab in other solid tumors where there remains an unmet medical need for new treatment options."

The phase 2 innovaTV 204 study (also known as GCT1015-04) is a global, multicenter, single arm trial that will enroll approximately 100 patients with recurrent and/or metastatic (2nd and 3rd line) cervical cancer who progressed on or relapsed after treatment with platinum-based chemotherapy used alone or in combination with bevacizumab (Avastin). Patients will be treated with single-agent tisotumab vedotin every three weeks. The primary endpoint of the trial is objective response rate as assessed by independent review. Key secondary endpoints include duration of response, progression-free survival, overall survival, safety and tolerability.

The companies also plan to evaluate tisotumab vedotin in multiple solid tumors in a phase 2 trial this year.

For more information about the phase 2 innovaTV 204 clinical trial of tisotumab vedotin, please visit www.clinicaltrials.gov, (Identifier: NCT03438396).

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 2018, with an estimated 4,000 deaths.1 Globally, cervical cancer remains one of the leading causes of cancer death in women globally, with over 260,000 women dying annually; the vast majority of these women being in the developing world.2 Routine medical examinations and the human papillomavirus (HPV) vaccine have lowered 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 and/or metastatic setting. 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 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 and Seattle Genetics’ ADC technology that utilizes a cleavable linker and the cytotoxic drug monomethyl auristatin E (MMAE). In cancer biology, Tissue Factor is a protein involved in tumor signaling and angiogenesis. Based on its high expression on many solid tumors and its rapid internalization, Tissue Factor was selected as a target for an ADC approach. In an earlier study, tisotumab vedotin demonstrated an encouraging response rate and manageable safety profile in patients with relapsed, recurrent and/or metastatic cervical cancer.

Tisotumab vedotin is being co-developed by Genmab A/S and Seattle Genetics, Inc.

On June 13, 2018 Nordic Nanovector ASA (OSE: NANO) reported that it has received approval from the Regional Committees for Medical and Health Research Ethics (REK) in Norway with regard to the Clinical Trial Application (CTA) for the Archer-1 Phase 1b trial with Betalutin (177Lu-satetraxetan-lilotomab) in combination with rituximab in second-line follicular lymphoma patients (2L FL) (Press release, Nordic Nanovector, JUN 13, 2018, View Source [SID1234553498]).

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Nordic Nanovector has now received all necessary approvals to begin Archer-1 in Norway and will commence start-up activities immediately. Archer-1 is a Phase 1b clinical trial designed to investigate the safety, tolerability, pharmacokinetic and preliminary efficacy of the Betalutin/rituximab combination in approx. 20 2L FL patients, and the study will initially be conducted in Norway. Further countries are expected to be added later. The first patient is expected to be dosed in the second half of 2018.

On June 13, 2018 BridgeBio Pharma reported the launch of CoA Therapeutics, a biopharmaceutical company developing novel small-molecules designed to increase Coenzyme-A (CoA) levels in genetic disorders where CoA deficiency is implicated (Press release, BridgeBio, JUN 13, 2018, https://investor.bridgebio.com/news-releases/news-release-details/bridgebio-pharma-launches-coa-therapeutics-target-coenzyme-rare [SID1234576279]). BridgeBio has committed funding to drive the program toward clinical studies. CoA Therapeutics’ lead compound will be entering the clinic in 2019 with a planned initial focus on pantothenate kinase-associated neurodegeneration, or PKAN.

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PKAN is an autosomal recessive genetic disorder caused by mutations in the pantothenate kinase 2 (PANK2) gene. The PANK2 enzyme plays a critical role in the synthesis of CoA, which is crucial in energy metabolism and implicated in a large number of developmental disorders. Patients with PKAN either have a complete absence or a significant deficiency of the PANK2 enzyme, which may lead to reduced CoA levels in the brain. There are currently no treatments approved for PKAN.

The CoA Therapeutics’ lead compounds, which were obtained under a license from St. Jude Children’s Research Hospital, were discovered and developed by St. Jude investigators Suzanne Jackowski, Ph.D., Charles Rock, Ph.D., Richard Lee, Ph.D., and Stephen White, Ph.D.

The prevalence of PKAN is estimated to be three in every 1,000,000 people. In the typical form of PKAN, symptoms present before the age of 10, and patients may rapidly experience neuronal degeneration, causing problems with movement, speech and vision.

"PKAN is a progressive, debilitating disease with no current approved therapy, and patients and their families currently rely on supportive treatments, which partially address the symptoms but not the root cause," said Shafique Virani, M.D., CEO of CoA. "We believe that our novel approach, using a highly brain-penetrant compound to directly target enzyme activity in neurons, can safely increase CoA levels, ease patients’ symptoms and make a meaningful difference in their quality of life. Our novel approach also holds promise for other diseases with defects in CoA metabolism, including the organic acidemias."

Joining Dr. Virani is Adam Shaywitz, M.D., Ph.D., who will serve as chief medical officer at CoA as well as CMO-in-residence at BridgeBio. Shaywitz was most recently executive director in clinical sciences at BioMarin Pharmaceuticals where he was involved in the design and planning of a number of clinical studies in rare disease including serving as program lead for the natural history and clinical treatment studies in Sanfilippo Syndrome B (MPS IIIB).

"We are privileged to be working with Drs. Jackowski, Rock, Lee and White, who have been at the forefront of CoA metabolism research in health and disease," said Neil Kumar, Ph.D., CEO of BridgeBio. "Their novel approach, which relies on increasing activity of the PANK enzyme family, is a great example of an allosteric agonist approach to potentially treat patients who have very few options."

On June 13, 2018 Sun BioPharma, Inc. (OTCQB:SNBP) and its wholly owned subsidiary, Sun BioPharma Australia Pty Ltd, a clinical stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with pancreatic diseases, reported that on June 4, 2018 the first patients were enrolled in a Phase 1a/1b study of SBP-101 in combination with gemcitabine and nabpaclitaxel for front-line treatment of patients with metastatic pancreatic ductal adenocarcinoma (PDA) (Press release, Sun BioPharma, JUN 13, 2018, View Source [SID1234527299]). Sun BioPharma Australia Pty Ltd, is the sponsor of this study. The Phase 1a portion of this study will treat up to 18 PDA patients in three cohorts in order to determine a recommended dose of SBP-101 to be given in combination with standard treatment. The Phase 1b portion will be an expansion at the recommended dose of SBP-101, and will guide SBP-101’s subsequent development for patients with PDA. This multi-center, front-line study has 3 sites in Australia, The Austin Health Cancer Trials Centre in Melbourne, The Adelaide Cancer Centre in Adelaide, The Blacktown Cancer and Haematology Centre in Sydney and one site in the United States, The University of Florida Health Cancer Center in Gainesville, Florida. The first patients have been enrolled at the Adelaide Cancer Centre in Adelaide, Australia under the direction of Associate Professor Dusan Kotasek and at the University of Florida Health Cancer Center in Gainesville, Florida under the direction of Thomas J. George, MD, F.A.C.P.

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Dr. Kotasek received his medical degree at the University of Adelaide and specialty training in Haemotology and Oncology at The Queen Elizabeth Hospital followed by a Fellowship at the University of Minnesota, in Minneapolis, MN, USA. A Co-Founder of the Adelaide Cancer Centre, Dr. Kotasek has published over 60 scientific papers in oncology, and he is one of Australia’s leading cancer clinical research experts. Dr. Kotasek, the Principal Investigator for this study at the Adelaide Cancer Centre commented, "Pancreatic cancer is a challenging disease with few significant options available with a meaningful impact on response rates and progression free survival. We are excited to participate in this clinical study, and to continue our evaluation of SBP-101 as front-line combination treatment for previously untreated patients with metastatic PDA."

Dr. George is a medical oncologist having graduated with honors from the University of Florida College of Medicine. He is the Director of the GI Oncology Program at the University of Florida and Associate Director of Clincial Investigation at the UF Health Cancer Center. He is the Principal Investigator for this study at the University of Florida Health Cancer Center and he commented, "We are extremely honored to be participating in this important study that was born from the discoveries made by Dr. Raymond Bergeron here at the University of Florida. Pancreatic cancer
requires us to think outside the box which is exactly what this treatment has the potential to offer our patients with PDA."

"Pancreatic cancer is a leading cause of cancer deaths in both Australia and the United States, currently being the 3rd most common cause of cancer deaths in the US. It represents a significant unmet medical need, with most patients having a poor prognosis and limited life expectancy," said Suzanne Gagnon, M.D., Chief Medical Officer at Sun BioPharma. "Our recently completed safety study in heavily pre-treated PDA patientssuggested SBP-101 could be a promising addition to current front-line treatment regimens. The Data Safety Monitoring Board, Principal
Investigators and our clinical team agreed to move directly to front-line for our second trial and we are excited to study SBP-101 in combination with standard of care chemotherapy for previously untreated metastatic PDA patients."

About SBP-101
SBP-101 is a first-in-class, proprietary, polyamine compound designed to exert therapeutic effects in a mechanism specific to the pancreas. Sun BioPharma originally licensed SBP-101 from the University of Florida Research Foundation in 2011. The molecule has been shown to be highly effective in preclinical studies of human pancreatic cancer models, demonstrating superior activity to existing FDA-approved chemotherapy agents. Combination therapy potential has also been shown for pancreatic cancer. SBP-101 is expected to differ from current pancreatic cancer
therapies in that it specifically targets the exocrine pancreas and has shown efficacy against primary and metastatic disease in animal models of human pancreatic cancer. Therefore management believes that SBP-101 may effectively treat both primary and metastatic pancreatic cancer, while leaving the insulin-producing islet cells and non-pancreatic tissue unharmed. The safety and metabolic profile demonstrated in our first-in-human safety study further supports
evaluation of the potential for additive or synergistic effects in combination with current standard pancreatic cancer treatment

On June 13, 2018 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, wet age-related macular degeneration and fibrotic diseases, reported that positive preclinical data from TRC105, TRACON’s endoglin antibody, in combination with a PD-1 antibody, were discussed in an oral presentation at the 2018 International Cancer Microenvironment Society meeting (Press release, Tracon Pharmaceuticals, JUN 13, 2018, View Source [SID1234527300]).

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Dr. Mark Schoonderwoerd of Leiden University presented data from multiple murine models assessing the activity of TRC105 in combination with a PD-1 antibody. The individual antibodies as well as the combination were studied in two separate models. In the first, immunocompetent mice were implanted with a syngeneic colorectal cancer subcutaneously to mimic metastatic colorectal cancer. In the second, immunocompetent mice were implanted orthotopically to mimic advanced colorectal cancer.

In both models, treatment with either TRC105 or a PD-1 antibody alone decreased tumor volume compared to IgG control antibody to a similar degree. However, combined treatment with TRC105 and the PD-1 antibody significantly reduced tumor volume compared to treatment with TRC105 or PD-1 treatment alone.

Treatment with either TRC105 or a PD-1 antibody improved survival to a similar degree compared to control antibody. However, survival was significantly improved with combination treatment versus the individual therapies, with long-term survival demonstrated in 30% to 60% of animals. Combination treatment also increased tumor specific T cells, indicating stimulation of an immune response.

The activity of TRC105 given as a single agent or combined with a PD-1 antibody was diminished following CD8+ T cell depletion, indicating that TRC105 activity was mediated through an immunologic mechanism.
In a separately reported third preclinical study, an endoglin antibody specific for mouse endoglin that mimics TRC105 activity in mice, M1043, was studied in a chemically induced colorectal cancer model of early-stage colorectal cancer.

Combined treatment with M1043 and a PD-1 antibody significantly reduced tumor volume compared to treatment with M1043 or PD-1 treatment alone. Combination treatment also significantly reduced the number of tumors that formed in response to the chemically induced carcinogenesis.
TRC105 is currently being studied in the ongoing pivotal randomized Phase 3 TAPPAS trial in angiosarcoma (NCT02979899), the randomized Phase 2 TRAXAR trial in renal cell carcinoma (NCT01806064), a Phase 1/2 trial in patients with hepatocellular carcinoma (NCT02560779), and a Phase 1 trial studying the combination of TRC105 and nivolumab (Opdivo) in patients with non-small cell lung cancer (NCT03181308).