On December 2, 2019 Boundless Bio, a company interrogating and targeting extrachromosomal DNA (ecDNA) in aggressive cancers, reported that it will present at the Piper Jaffray 31st Annual Healthcare Conference in New York, NY (Press release, Boundless Bio, DEC 2, 2019, View Source [SID1234551841]).

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Zachary Hornby, President and Chief Executive Officer of Boundless Bio, will give a company overview on Thursday, Dec. 5, 2019 from 2:50 – 3:10 p.m. EST.

About ecDNA

Extrachromosomal DNA, or ecDNA, are large circles of DNA containing genes that are outside the cells’ chromosomes and can make many copies of themselves. ecDNA can be rapidly replicated within the cell, causing high numbers of oncogene copies, a trait that can be passed to daughter cells in asymmetric ways during cell division. Cells have the ability to upregulate or downregulate ecDNA and resulting oncogenes to ensure survival under selective pressures, including chemotherapy or radiation, making ecDNA one of cancer cells’ primary mechanisms of recurrence and treatment evasion. ecDNA are rarely seen in healthy cells but are found in many solid tumor cancers. They are a key driver of the most aggressive and difficult-to-treat cancers, specifically those characterized by high copy number amplification of oncogenes

On December 2, 2019 NantKwest, Inc. (Nasdaq: NK), a clinical-stage natural killer cell-based therapeutics company, reported promising safety data generated from the first six patients in its QUILT-3.064 trial (Press release, NantKwest, DEC 2, 2019, View Source [SID1234551840]). The first-in-human study evaluated the safety and preliminary efficacy of the Company’s first-in-class, tumor-targeted PD-L1.t-haNK cell therapy in patients with locally advanced or metastatic solid tumors.

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"The unique dual-targeting of PD-L1.t-haNK to both PD-L1 expressing tumors and therapeutic monoclonal antibodies has the potential to be transformative to the treatment of advanced solid tumors with cell-based therapies," said Dr. Patrick Soon-Shiong, the Chairman and CEO of NantKwest. "PD-L1.t-haNK is a cryopreserved, off-the-shelf product that can rapidly deliver treatment to patients in an outpatient setting while avoiding the extensive manufacturing delays associated with autologous CAR-T therapies. We look forward to reporting full study results from the phase 1 cohort and moving toward a recommended phase 2 dose. We continue to advance our innovative cell therapies such as PD-L1.t-haNK in combination with ImmunityBio’s N-803, an IL-15 superagonist that is designed to stimulate the activation and proliferation of the patient’s own NK cells to maximize the potential of immunogenic cell death to treat cancer," continued Soon-Shiong. NantKwest and a wholly owned subsidiary of ImmunityBio have entered into an exclusive collaboration agreement to co-develop NantKwest’s proprietary off-the-shelf NK platforms in combination with N-803.

On December 2, 2019 at the NantKwest Key Opinion Leader and Investors conference, Dr. Soon-Shiong described the clinical development plans for two of NantKwest’s first-in-class NK products: haNK, which was developed to target binding to approved monoclonal therapies such as Trastuzumab, Rituximab and Cetuximab; and PD-L1.t-haNK, which was also designed to target these approved therapies plus directly target PD-L1-expressing tumor cells.

PD-L1.t-haNK cells are a human-derived, allogeneic, natural killer cell line engineered to express a chimeric antigen receptor (CAR) targeting PD-L1, whose origins arise from NantKwest’s proprietary NK-92 (aNK) master cell bank. In addition to targeting PD-L1, PD-L1.t-haNK is engineered to produce intracellular IL-2 for enhanced CD16-targeted antibody-dependent cellular cytotoxicity capabilities.

John Lee, M.D., Clinical Senior Vice President at NantKwest, said, "We are highly encouraged by the early safety results with PD-L1.t-haNK in a patient population with advanced, difficult to treat solid tumors. All patients were able to be infused in the outpatient setting without any reported cytokine toxicities or immune related adverse events. NantKwest’s approach has been designed to overcome the challenges and limitations typically seen when treating solid tumors with CAR-T and other immunotherapy approaches and I look forward to progressing our studies to advance this innovative new approach to cancer therapy."

Study Design

The QUILT-3.064 study is an open-label, Phase 1 study of PD-L1.t-haNK in subjects with locally advanced or metastatic solid cancers to evaluate safety, preliminary efficacy, determine maximum tolerated dose (MTD) or highest tolerated dose (HTD) and designate the recommended Phase 2 dose (RP2D). The study is being conducted in two parts: the first is evaluating dose escalation using a 3 + 3 design and the second part will evaluate the expansion of the recommended Phase 2 dose (RP2D) to further assess the safety and efficacy of PD-L1.t-haNK therapy. In part one, six subjects were sequentially enrolled, starting at dose level 1 and assessed for dose-limiting toxicities. The primary study objectives are to determine the MTD or HTD, RP2D (recommended phase 2 dose), and safety. The secondary endpoints include objective response rate (ORR), progression free survival (PFS) and overall survival (OS). More information can be found at ClinicalTrials.gov, Identifier: NCT04050709.

On December 2, 2019 Epizyme, Inc. (Nasdaq: EPZM), a late-stage biopharmaceutical company developing novel epigenetic therapies, reported that the Oncologic Drugs Advisory Committee (ODAC) of the U.S. Food and Drug Administration (FDA) is scheduled to review data supporting the company’s New Drug Application (NDA) requesting accelerated approval for tazemetostat, an oral, first-in-class EZH2 inhibitor, at a meeting on Dec. 18, 2019 at 1:00 p.m. ET (Press release, Epizyme, DEC 2, 2019, View Source [SID1234551839]). The proposed indication to be discussed at this upcoming ODAC meeting is for tazemetostat for the treatment of patients with metastatic or locally advanced epithelioid sarcoma not eligible for curative surgery.

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ODAC is an independent panel of experts that evaluates data concerning the efficacy and safety of marketed and investigational products for use in the treatment of cancer and makes appropriate recommendations to the FDA. Although the FDA will consider the recommendation of the panel, the final decision regarding the approval of a product is made solely by the FDA.

Epizyme announced on July 25, 2019 that the FDA had accepted for filing the NDA for tazemetostat for the treatment of patients with metastatic or locally advanced epithelioid sarcoma not eligible for curative surgery with Priority Review and a Prescription Drug User-Fee Act (PDUFA) action date of Jan. 23, 2020. Epizyme’s NDA submission is based primarily on data from the 62 patient epithelioid sarcoma cohort of its ongoing Phase 2 study of tazemetostat.

On December 2, 2019 Amphivena Therapeutics, Inc., a private clinical stage immuno-oncology company developing T cell engager therapeutics for cancer, reported that Curtis L. Ruegg, Ph.D. will join the company as its new President and Chief Executive Officer and will also sit on the company’s Board of Directors (Press release, Amphivena Therapeutics, DEC 2, 2019, View Source [SID1234551838]). The company’s Founder and current President and Chief Executive Officer, Jeanmarie Guenot, Ph.D., will transition into an Advisory role.

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Dr. Ruegg joins Amphivena from Parvus Therapeutics, where he was President and Chief Executive Officer. With more than 25 years of biopharmaceutical experience, he brings strong drug development expertise to Amphivena. Prior to Parvus, Dr. Ruegg filled various leadership roles at Revance, CoTherix, Intermune, AP Cells and Dendreon.

"I am excited to join Amphivena at this critical inflection point," said Dr. Ruegg. "Its lead investigational candidate, AMV564, has advanced in clinical development in both hematologic cancers and in solid tumors, with initial clinical trial data reading out as early as 2020. The momentum created by the team to date is significant and I look forward to helping to build Amphivena into a leading immuno-oncology company."

Executive Chairman Peter Van Vlasselaer, Ph.D., said, "Since the company’s inception, Jeanmarie has guided its leadership team to establish a preeminent position in the T cell engagement space, most recently by expanding the application of AMV564 beyond hematologic cancers to solid tumors. We thank her for her dedication to the company and look forward to her continued involvement with the company in her Advisory role. We welcome Curtis and look forward to his contributions as the company matures. I am enthusiastic about our prospects as we further cement Amphivena’s leadership in the T cell engager and immuno-oncology arenas."

About AMV564

AMV564 is a bivalent, bispecific (2:2) T cell engager that binds CD33 and CD3. The company announced in October initiation of a Phase 1 trial to evaluate the effect of AMV564 on these immune suppressive cells and the potential therapeutic benefit of relieving this important source of T cell suppression in patients with solid tumors. To date, over 50 patients have received AMV564 in two Phase 1 clinical trials for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). It is also currently being evaluated in a First-in-Human Phase 1 trial in patients with relapsed/refractory AML at Washington University School of Medicine, MD Anderson Cancer Center, New York-Presbyterian/Weill Cornell Medical Center and Weill Cornell Medicine, Fred Hutchinson Cancer Research Center, The Ohio State University Wexner Medical Center, University of Pennsylvania Medical Center, Northwestern Memorial Hospital, and The Johns Hopkins Hospital.

The safety, efficacy and selectivity of AMV564 was highlighted most recently at both the 24th European Hematology Association (EHA) (Free EHA Whitepaper) meeting in Amsterdam (Abstract S877) and at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, CA last December. Amphivena believes that AMV564 has demonstrated novel clinical activity by rapidly and selectively eliminating leukemic blasts and rare immature, granulocytic and monocytic MDSCs while sparing normal CD33-expressing cells, including neutrophils and monocytes.

On December 2, 2019 PellePharm, Inc., a BridgeBio Pharma, Inc. (Nasdaq: BBIO) company, reported the completion of enrollment for its pivotal Phase 3 clinical trial of Patidegib Topical Gel 2% vs. vehicle gel in patients with Gorlin Syndrome (Press release, PellePharm, DEC 2, 2019, View Source [SID1234551837]). PellePharm is a late clinical-stage biopharmaceutical company committed to targeting rare forms of basal cell carcinoma.

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"Patients living with Gorlin Syndrome undergo recurring, invasive surgical treatments that result in facial scarring, potential loss of vital facial structure and function, and impact to their quality of life," said Sanuj K. Ravindran, M.D., president and chief executive officer of PellePharm. "Significant enthusiasm for the trial allowed us to enroll the study quickly, but only after enrolling approximately 16% more patients than originally planned to accommodate the incredible interest from patients. We continue to be encouraged about Patidegib Topical Gel’s potential and are grateful for the overwhelming support of the Gorlin Syndrome community worldwide, including the researchers, clinicians, patients and caregivers working diligently to bring promise to this devastating disease."

The randomized, double-blind, vehicle-controlled Phase 3 trial is evaluating the safety and efficacy of Patidegib Topical Gel 2% applied, twice daily to the face over 12 months vs. vehicle gel. An open-label safety and tolerability extension study is planned for at least 12 months following the end of the study for patients who complete the Phase 3 trial, and for those who completed the Phase 2 Gorlin Syndrome trial.

"This is a very important milestone for PellePharm and the broader Gorlin Syndrome community, and we’re thrilled to be one step closer to our goal of bringing Patidegib Topical Gel to patients living with Gorlin Syndrome, a condition for which there is no FDA-approved therapy," said Thorsten Thormann, vice president of global research at LEO Pharma.

As of November 2018, PellePharm and LEO Pharma entered into a strategic collaboration to address the unmet medical needs for rare skin conditions, such as Gorlin Syndrome and High Frequency Basal Cell Carcinoma (HF-BCC). LEO Pharma is providing resources to PellePharm to fund, amongst other activities, its Phase 3 trial of Patidegib Topical Gel 2% in patients with Gorlin Syndrome under the terms of the agreement.

About Patidegib

Patidegib Topical Gel, an investigational treatment, is designed to reduce the BCC tumor burden in patients with Gorlin Syndrome and High Frequency BCC (HF-BCC) by blocking the disease at its source within the hedgehog signaling pathway. Patidegib Topical Gel has shown early promise in a Phase 2 clinical study for the mitigation of BCC tumors in Gorlin Syndrome. The topical formulation of Patidegib was developed with a goal of providing the clinical activity previously demonstrated by oral Patidegib in Phase 1 trials and a favorable tolerability profile without the adverse systemic side effects observed with the oral class of hedgehog inhibitors. The topical gel formulation is stable at room temperature for at least two years, potentially making it an option for ongoing, at-home management of Gorlin Syndrome and HF-BCC. PellePharm has received both Orphan Drug Designation and Breakthrough Therapy Designation for Patidegib Topical Gel in Gorlin Syndrome from the FDA, as well as Orphan Drug Designation in Gorlin Syndrome from EMA’s Committee for Orphan Medicinal Products in the EU.

About Gorlin Syndrome

Gorlin Syndrome is a rare, genetic disease characterized by constitutional, heritable mutations in one allele of the tumor suppressor gene encoding PATCHED1 (PTCH1), which acts as the primary inhibitor of the hedgehog signaling pathway. This leads to the formation of multiple basal cell carcinomas, often on the face.

With no FDA-approved drugs available for patients with Gorlin Syndrome, the standard of care for treating BCCs is surgery. People with severe Gorlin Syndrome may have as many as 30 surgeries per year, which can be repetitive, scarring and disfiguring. Approximately 10,000 people in the United States, or one in 31,000, are believed to be affected by Gorlin Syndrome. Gorlin Syndrome is known by several names, including Gorlin-Goltz Syndrome, Basal Cell Nevus Syndrome (BCNS) and Nevoid Basal Cell Carcinoma Syndrome (NBCCS).

About High Frequency Basal Cell Carcinoma (HF-BCC)

High Frequency BCC, like Gorlin Syndrome, is a rare disease which is characterized by the development of an abnormally high number of BCCs. Unlike patients with Gorlin Syndrome, patients with HF-BCC are not born with a germline PTCH1 mutation and do not suffer from the other systemic manifestations of Gorlin Syndrome. The standard of care for patients with HF-BCC is surgery.