SpringWorks Therapeutics Announces Initiation of Phase 3 Trial (DeFi) of Nirogacestat in Adult Patients with Desmoid Tumors

On May 20, 2019 SpringWorks Therapeutics, a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported that the first patient has been dosed in the Phase 3 "DeFi" (Desmoid/Fibromatosis) trial evaluating nirogacestat, an oral, selective, small molecule gamma-secretase inhibitor, in adult patients with progressing desmoid tumors (Press release, SpringWorks Therapeutics, MAY 20, 2019, View Source [SID1234536485]).

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Desmoid tumors are rare and often debilitating and disfiguring soft-tissue tumors that can aggressively invade surrounding healthy tissues, including joints, muscles, blood vessels, nerves and internal organs. Depending on their size and location, desmoid tumors can cause significant morbidities, including severe pain, disfigurement, internal bleeding, debilitating loss of range of motion, and, in rare cases, desmoid tumors can be fatal.1 It is estimated that 1,000 to 1,500 new cases of desmoid tumors are diagnosed each year in the United States.2,3 There are currently no therapies approved by the U.S. Food and Drug Administration (FDA) for the treatment of desmoid tumors.

"For patients living with these debilitating tumors, the DeFi trial marks a meaningful step forward in what we hope will result in the first approved treatment for this underserved patient community," said Saqib Islam, Chief Executive Officer of SpringWorks Therapeutics. "I am grateful for the persistence of our partners, colleagues and the patient advocacy community, whose collective efforts made it possible for SpringWorks to advance nirogacestat into our Phase 3 DeFi trial. We look forward to enrolling patients to confirm the clinical benefits of nirogacestat for people with desmoid tumors."

In June 2018, the FDA granted Orphan Drug designation for nirogacestat for the treatment of desmoid tumors, and in November 2018, the FDA granted Fast Track designation for nirogacestat for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis.

About the DeFi Trial

The DeFi trial is a global, randomized, double-blind, placebo-controlled Phase 3 trial to evaluate the efficacy, safety and tolerability of nirogacestat in adult patients with progressing desmoid tumors. The study will enroll approximately 100 adult patients, who will receive 150 mg of nirogacestat or placebo twice daily. Key eligibility criteria include tumor progression by ≥20% as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) within 12 months prior to the first dose of study treatment.

The primary endpoint is progression-free survival (PFS), defined as the time from randomization until the date of assessment of progression or death by any cause using RECIST 1.1. Secondary endpoints include safety and tolerability measures, as well as overall response rate, tumor volume changes as assessed by MRI, and changes in baseline in patient-reported outcomes.

More information about the DeFi trial is available at www.clinicaltrials.gov under the identifier NCT03785964.

About Desmoid Tumors

Desmoid tumors (also referred to as aggressive fibromatosis or desmoid-type fibromatosis) are rare and often debilitating and disfiguring soft tissue tumors characterized by a growth pattern that can aggressively invade surrounding healthy tissues, including joints, muscles, blood vessels, nerves and internal organs. While they can arise in any part of the body, the most common sites are the upper and lower extremities, abdominal walls, thoracic areas, and the head and neck. The severity of desmoid tumors and associated symptoms varies based on their size, location and the aggressiveness of the growth pattern. Desmoid tumors can cause significant morbidities, including severe pain, disfigurement, internal bleeding, debilitating loss of range of motion, and, in rare cases, desmoid tumors can be fatal.1

Desmoid tumors can affect children and adults, and are more commonly diagnosed in young adults between 20-30 years of age, with a two-to-three-fold predominance in females.1,4 It is estimated that desmoid tumors affect 2 to 5 per million people worldwide, and that there are 1,000 to 1,500 new cases diagnosed per year in the United States.2,3

Historically, desmoid tumors were treated with surgical resection or in severe cases, amputation, but even with these interventions, high rates of tumor regrowth have been observed.5 There are currently no FDA-approved therapies for the treatment of desmoid tumors.

About Nirogacestat

Nirogacestat is an investigational, oral, selective, small molecule gamma-secretase inhibitor. Gamma secretase cleaves multiple transmembrane protein complexes, including Notch, which is believed to play a role in activating pathways that contribute to desmoid tumor growth.

Nirogacestat has been investigated in 24 patients with desmoid tumors across Phase 1 and Phase 2 clinical trials. In these studies, treatment with nirogacestat demonstrated 100% disease control rate as measured by RECIST criteria, and median PFS was not reached by the time of publication in either trial due to lack of tumor progression events. Nirogacestat also showed an encouraging tolerability profile in these earlier studies, with many patients remaining on treatment for years and only one patient in the combined trials discontinuing due to an adverse event. The most common adverse events in prior studies were diarrhea, skin disorders and hypophosphatemia.

Oragenics, Inc. Provides Development Update of AG013 for Oral Mucositis

On May 20, 2019 Oragenics, Inc. (NYSE American: OGEN), a leader in the development of new antibiotics against infectious diseases and effective treatments for oral mucositis ("OM"), reported development updates regarding the Company’s lead compound for OM, AG013 (Press release, Oragenics, MAY 20, 2019, View Source [SID1234536484]). These developments include the enrollment of over 80 patients in the Company’s Phase 2 clinical of AG013 and, in addition, the World Health Organization has provided the Company with the generic name of dapatifagene navolactibac for the AG013 compound.

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"We continue to increase the number of clinical sites across the globe with 48 of the 61 identified clinical sites actively enrolling patients for our Phase 2 clinical trial of AG013," stated Alan Joslyn, Ph.D., President and Chief Executive Officer of Oragenics, Inc. "In the meantime, we are pleased to have an agreed upon generic designation for AG013, which will now also be referred to as dapatifagene navolactibac, to allow us a more specific way of referring to the compound moving forward. We anticipate providing further updates as developments warrant."

The ongoing Phase 2 trial is a double-blind, placebo-controlled, two-arm, multi-center trial, in which approximately 200 patients will be randomized in a 1:1 ratio to receive either dapatifagene navolactibac or placebo. The purpose of the study (NCT03234465) is to evaluate the safety, tolerability and efficacy of topically administered dapatifagene navolactibac compared to placebo for reducing the incidence and severity of OM in patients undergoing traditional chemoradiation for the treatment of head and neck cancer. Key measures include duration, time to development, and overall incidence of OM (using a World Health Organization scale) during the active treatment phase, which begins from the start of chemoradiation therapy and ends two weeks following its completion.

Dapatifagene navolactibac, which has been granted Fast Track designation with the U.S. Food and Drug Administration and orphan drug status in Europe, is an Intrexon Actobiotics therapeutic candidate formulated to deliver the therapeutic molecule, human Trefoil Factor 1, to the mucosal tissues in the oral cavity in a convenient oral rinsing solution. Trefoil Factors are a class of peptides involved in the protection of gastrointestinal tissues against mucosal damage and play an important role in these tissues’ subsequent regeneration. The compound was designed by the Company’s strategic partner, Intrexon Actobiotics NV, a wholly-owned subsidiary of Intrexon Corporation (NYSE: XON) whereby Oragenics, Inc. holds an exclusive world-wide license.

Veracyte Unveils Next-Generation Percepta Genomic Sequencing Classifier for Improved Lung Cancer Diagnosis

On May 20, 2019 Veracyte, Inc. (Nasdaq: VCYT), a leading genomic diagnostics company, reported new data demonstrating that its next-generation Percepta Genomic Sequencing Classifier (GSC) provides expanded lung cancer risk information that can further guide next steps for patients with lung nodules (Press release, Veracyte, MAY 20, 2019, View Source [SID1234536483]).

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Researchers prospectively validated the Percepta GSC on 412 patients with lung nodules who had inconclusive results following bronchoscopy, a common nonsurgical procedure to diagnose lung cancer. Among patients with an "intermediate" pre-test risk of cancer – the group that accounts for the majority of lung nodules – the Percepta GSC demonstrated high accuracy when it down-classified patients to "low risk" for cancer (negative predictive value of 91 percent). The test also had a positive predictive value (PPV) of 65 percent when it up-classified patients to "high risk" for cancer. The American College of Chest Physicians recommends patients with a cancer risk of 65 percent or greater undergo surgical treatment.

The new findings will be shared this evening at a company event being held during the American Thoracic Society 2019 International Conference(ATS 2019) in Dallas.

"Determining whether lung nodules are benign or cancerous is often difficult, which can lead to unnecessary invasive procedures and treatment delays," said Giulia C. Kennedy, Ph.D., chief scientific and medical officer of Veracyte. "With its ability to both down-classify and up-classify patients with inconclusive lung nodules, the Percepta GSC should help physicians avoid invasive biopsies in patients who are at low risk of lung cancer, while helping to guide intervention steps for those at high risk."

The Percepta GSC utilizes novel "field of injury" science – which identifies genomic changes associated with lung cancer in current or former smokers using a simple brushing of the person’s airway. The test is also Veracyte’s third clinical classifier to be developed on the company’s novel RNA whole-transcriptome sequencing and machine learning platform. Veracyte plans to begin making the Percepta GSC available to physicians by the middle of 2019.

"We are excited to unveil our Percepta GSC, which we believe will improve diagnosis and treatment decisions for patients undergoing evaluation for lung cancer," said Bonnie Anderson, Veracyte’s chairman and chief executive officer. "Additionally, we believe that moving the Percepta classifier to our RNA whole-transcriptome sequencing platform – together with our Afirma and Envisia classifiers – will provide operational efficiencies and a robust foundation for continued innovation. This includes our development of the first nasal swab test for early lung cancer detection."

Lung cancer is the leading cause of cancer deaths worldwide. In the United States, lung cancer causes more than 154,000 deaths each year – more than the next three most prevalent cancers combined. Because lung cancer is difficult to diagnose before it has metastasized, only 16 percent of cases are detected at an early stage, when the disease is more treatable. Lung cancer’s five-year survival rate is only 18 percent, much lower than that of other common cancers. Approximately 80 percent of lung cancer deaths are caused by smoking. Veracyte estimates that approximately 350,000 bronchoscopies are currently performed each year to evaluate suspicious lung nodules for cancer and that up to 70 percent of these produce inconclusive results.

Also during the ATS 2019 conference, Kevin Flaherty, M.D., of the University of Michigan Health System, will present clinical utility data demonstrating that Veracyte’s Envisia Genomic Classifier improves diagnosis of idiopathic pulmonary fibrosis (Session D12, Abstract A5837). These data were published online in The Lancet Respiratory Medicine on April 1, 2019.

Stemline Therapeutics Announces ELZONRIS Clinical Data Selected for Presentation at Upcoming EHA Annual Congress

On May 20, 2019 Stemline Therapeutics, Inc. (Nasdaq: STML), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics, reported that ELZONRIS (tagraxofusp) clinical data in blastic plasmacytoid dendritic cell neoplasm (BPDCN), chronic myelomonocytic leukemia (CMML), and myelofibrosis (MF) have been selected for poster presentations at the upcoming 24thCongress of the European Hematology Association (EHA) (Free EHA Whitepaper), to be held from June 13-16, 2019, in Amsterdam (Press release, Stemline Therapeutics, MAY 20, 2019, View Source [SID1234536482]).

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Details on the presentations are as follows:

Results from Ongoing Phase 1/2 Clinical Trial of Tagraxofusp (SL-401) in Patients with Relapsed/Refractory Chronic Myelomonocytic Leukemia (CMML)

• Abstract: PF672
• Presenter: Mrinal M. Patnaik, MBBS; Mayo Clinic
• Date: Friday, June 14
• Time: 5:30-7:00 PM CET
Results from Ongoing Phase 1/2 Clinical Trial of Tagraxofusp (SL-401) in Patients with Intermediate, or High Risk, Relapsed/Refractory Myelofibrosis (MF)

• Abstract: PF668
• Presenter: Naveen Pemmaraju, MD; The University of Texas MD Anderson Cancer Center
• Date: Friday, June 14
• Time: 5:30-7:00 PM CET
Results of Pivotal Phase 2 Clinical Trial of Tagraxofusp (SL-401) in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

• Abstract: PS1063
• Presenter: Naveen Pemmaraju, MD; The University of Texas MD Anderson Cancer Center
• Date: Saturday, June 15
• Time: 5:30-7:00 PM CET
Please visit the BPDCN disease awareness booth (#1351) during the 24thCongress of EHA (Free EHA Whitepaper).

About ELZONRIS
ELZONRIS (tagraxofusp-erzs), a CD123-directed cytotoxin, is approved by the U.S. Food and Drug Administration (FDA) and commercially available in the U.S. for the treatment of adult and pediatric patients, two years or older, with blastic plasmacytoid dendritic cell neoplasm (BPDCN). For full prescribing information in the U.S., visit www.ELZONRIS.com. In Europe, a marketing authorization application (MAA) is under review by the European Medicines Agency (EMA). ELZONRIS is also being evaluated in additional clinical trials in other indications including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), and acute myeloid leukemia (AML).

About BPDCN
BPDCN is an aggressive hematologic malignancy with historically poor outcomes and an area of unmet medical need. BPDCN typically presents in the bone marrow and/or skin and may also involve lymph nodes and viscera. The BPDCN cell of origin is the plasmacytoid dendritic cell (pDC) precursor. The diagnosis of BPDCN is based on the immunophenotypic diagnostic triad of CD123, CD4, and CD56, as well as other markers. For more information, please visit the BPDCN disease awareness website at www.bpdcninfo.com.

About CD123
CD123 is a cell surface target expressed on a wide range of myeloid tumors including blastic plasmacytoid dendritic cell neoplasm (BPDCN), certain myeloproliferative neoplasms (MPNs) including chronic myelomonocytic leukemia (CMML) and myelofibrosis (MF), acute myeloid leukemia (AML) (and potentially enriched in certain AML subsets), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). CD123 has also been reported on certain lymphoid malignancies including multiple myeloma (MM), acute lymphoid leukemia (ALL), hairy cell leukemia (HCL), Hodgkin’s lymphoma (HL), and certain Non-Hodgkin’s lymphomas (NHL). In addition, CD123 has been detected on some solid tumors as well as autoimmune disorders including cutaneous lupus and scleroderma.

Phio Pharmaceuticals to Present at Sachs Associates 5th Annual Immuno-Oncology BD&L and Investment Forum

On May 20, 2019 Phio Pharmaceuticals Corp. (NASDAQ: PHIO), a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (sd-rxRNA) therapeutic platform, reported that it will be presenting at the Sachs Associates 5th Annual Immuno-Oncology BD&L and Investment Forum in Chicago (Press release, Phio Pharmaceuticals, MAY 20, 2019, View Source [SID1234536481]).

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Dr. Gerrit Dispersyn, Dr. Med. Sc., President and CEO, will present an overview of the Company’s RNAi technology, its relevance in immuno-oncology and an update on the Company’s product development activities in this field. The presentation will be held in Track B of the Faulkner Room of the Waldorf Astoria Chicago Hotel at 11:50 AM CT on May 31, 2019.

The presentation will be available under the "Investors – Events and Presentations" section of the Company’s website, www.phiopharma.com, approximately one hour following the presentation.

The Company will also be attending the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held at McCormick Place in Chicago from May 31 – June 4, 2019 and will be available for investor and company meetings throughout the conferences.