On June 12, 2019 NuCana plc (NASDAQ: NCNA) reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for the Company’s investigational drug, Acelarin (NUC-1031), for the treatment of biliary tract cancer (Press release, Nucana BioPharmaceuticals, JUN 12, 2019, View Source [SID1234537054]). Acelarin is a new chemical entity and is NuCana’s ProTide transformation of gemcitabine.

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"We are pleased to have received orphan drug designation from the FDA for Acelarin in biliary tract cancer," said Hugh Griffith, NuCana’s Founder and Chief Executive Officer. "There is a high unmet need for patients suffering from this cancer type. Our Phase Ib study of Acelarin combined with cisplatin showed an approximate doubling of the response rate expected with the standard of care, gemcitabine plus cisplatin, with several patients achieving significant reductions in their tumor volume as well as further tumor shrinkage over time. We believe Acelarin represents a potential significant advance in biliary tract cancer and we remain on track to open our global Phase III study in combination with cisplatin as a front-line treatment for patients with advanced biliary tract cancer in 2019."

Orphan drug designation is granted by the FDA to drugs that are defined as those intended for the treatment, prevention or diagnosis of rare diseases or conditions that affect fewer than 200,000 people in the United States. Orphan drug designation provides certain benefits and incentives that may include tax credits towards the cost of clinical trials and prescription drug user fee waivers.

About Biliary Tract Cancer

Biliary tract cancer is a form of cancer that develops in the bile duct system, which connects the liver, gallbladder, and small intestine, moving bile – a fluid that helps digest fats – to the small intestine. Approximately 178,000 new cases of biliary tract cancer are diagnosed each year worldwide, with more than 12,000 of those diagnoses in the United States.

On June 12, 2019 Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, reported that the first patient has been dosed in a Phase 1/2 study evaluating the investigational agent TP-0903, an AXL receptor tyrosine kinase (RTK) inhibitor, in patients with previously treated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) (Press release, Tolero Pharmaceuticals, JUN 12, 2019, View Source [SID1234537051]). The open-label, dose-escalation, safety, pharmacokinetics, and pharmacodynamic study will evaluate the dose-limiting toxicities and clinical activity of oral TP-0903 administered in patients with previously treated CLL/SLL, as monotherapy or in combination with ibrutinib.

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"Although there have been significant advances in the treatment of CLL and SLL in recent years, there remains an area of clinical unmet need for patients who have had disease progression or relapse with available therapies." said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals. "The initiation of this study will allow us to learn more about the clinical profile of TP-0903 and the role of AXL receptor tyrosine kinase (RTK) inhibition in patients with previously treated CLL and SLL."

The primary outcome measures of the Phase 1 study are to determine dose-limiting toxicities and the incidence of treatment-emergent adverse events of oral TP-0903 administered once daily for 28 days in patients with previously treated CLL/SLL. Secondary outcome measures of the Phase 1 study include pharmacokinetics. The recommended Phase 2 dose (RP2D) will be determined in Phase 1 of the study. Phase 2 of the study will begin after the completion of Phase 1. The primary outcome measure of Phase 2 will be to determine the objective response rate according to guidelines set forth by the 2018 International Workshop on CLL. Secondary outcome measures of the Phase 2 study include assessment of duration of response and rate of overall survival.

In Phases 1 and 2 of the study, patients will be assigned to one of two defined patient groups. Patients in Group 1, which includes those who are intolerant to or have progressed on B-cell receptor antagonists and/or BCL-2 antagonists, will receive TP-0903 monotherapy. Patients in Group 2, which includes those who have progression of disease on ibrutinib and the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient, will receive combination therapy of TP-0903 and ibrutinib. Additional information on this trial, including comprehensive inclusion and exclusion criteria, can be accessed at www.ClinicalTrials.gov (NCT03572634).

About TP-0903
TP-0903 is an investigational oral AXL receptor tyrosine kinase (RTK) inhibitor under evaluation in a Phase 1/2 study in patients with CLL/SLL (NCT03572634) and a Phase 1b study in patients with advanced solid tumors (NCT02729298). Tolero is exploring parallel clinical development paths for TP-0903 in both solid and hematologic malignancies.

About AXL Kinase
AXL belongs to the TAM (Tyro3, AXL and Mer) family of receptor tyrosine kinases and is overexpressed in many human cancers.1 It plays a key role in tumor cell proliferation, survival, metastasis, cellular adhesion and avoidance of the immune response. The overexpression of AXL is associated with a poor patient prognosis and drug resistance.2

On June 12, 2019 Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported that management will present at the upcoming Raymond James Life Sciences and MedTech Conference taking place June 18-19, 2019 in New York, NY (Press release, Zymeworks, JUN 12, 2019, View Source [SID1234537050]).

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The Company’s presentation will be on Wednesday, June 19, 2019 at 11:30 a.m. ET.

On June 12, 2019 OnKure, Inc. and the University of Colorado Cancer Center reported enrollment of the first patient in a first-in-human phase 1 clinical trial testing investigational anti-cancer agent OKI-179, a novel and Class-selective HDAC inhibitor, in patients with advanced solid tumors (Press release, OnKure, JUN 12, 2019, View Source [SID1234537049]). The study represents a milestone in the ongoing partnership between OnKure and the University of Colorado system, with the drug discovery and development company built around basic research from CU Boulder and the clinical trial taking place in partnership with CU Cancer Center on the Anschutz Medical Campus.

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"This CU homegrown, clinical-stage drug is the result of a multi-year collaboration, so our team is very excited. We’re happy to report that we successfully dosed the first patient and the patient is doing well," says Jennifer Diamond, MD, Medical Director of the CU Cancer Center Cancer Clinical Trials Office, Co-director of the Women’s Cancer Developmental Therapeutics Program, and principal investigator of the OKI-179 phase 1 clinical trial.

OKI-179 is a potent and selective inhibitor of a family of enzymes known as histone deacetylases (HDACs), specifically inhibiting Class 1 HDACs, which are implicated in the development and growth of a range of solid and hematologic cancers. While previous HDAC inhibitors have shown promise in preclinical studies, clinical benefit has generally been limited by toxicity.

"We’re very optimistic that OKI-179 will fill a hole in what is currently available," says Anthony D. Piscopio, PhD, President and Chief Executive Officer of OnKure. "It also stands out from FDA-approved HDAC inhibitors based on its unique potency and selectivity profile."

The compound is an analog of the naturally occurring chemical largazole, named for Key Largo, Florida, where largazole is bio-manufactured by a type of coral-colonizing bacteria indigenous to the region. After its structure and anti-proliferative effects were described in 2008, work by Xuedong Liu, PhD, Professor of Chemistry and Biochemistry at CU Boulder, showed that largazole and the chemical analog that would become OKI-179 achieve their anti-proliferative effects through the mechanism of HDAC inhibition. Dr. Liu also serves as Chief Science Officer of OnKure.

"Basically, HDAC enzymes remove a kind of speed limiter from cells, allowing them to proliferate more readily and HDAC inhibitors like OKI-179 block this effect," Dr. Diamond says.

The phase 1 clinical trial (NCT03931681) is offered exclusively at CU Cancer Center to patients with solid tumors for whom no standard therapy exists, and is meant to explore drug safety, tolerability, and dosing. Additional research, including a 2017 study by CU Cancer Center investigators published in the Journal of Clinical Oncology, shows that in addition to possible single-agent use, OKI-179 may sensitize tumor tissue to targeting via immunotherapies including anti-PD1 checkpoint inhibitors.

"This drug is a compelling part of our portfolio of innovative clinical trials in the CU Cancer Center Women’s Cancer Developmental Therapeutics Program," Dr. Diamond says.

On June 12, 2019 Prelude Therapeutics, a privately held, clinical-stage biopharmaceutical company focused on the discovery and development of small molecule drugs that target key drivers of cancer cell growth, survival and resistance, secured $60 million in Series B financing; taking its total investments to date to $95 million (Press release, Prelude Therapeutics, JUN 12, 2019, View Source [SID1234537048]). The financing was co-led by Prelude’s two existing institutional investors, including OrbiMed Advisors LLC.

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Since its launch in July 2016, Prelude has made rapid progress in its first discovery program targeting Protein Arginine Methyltransferase 5 (PRMT5), a member of the arginine methyltransferase family. PRMT5 plays an important role in several cellular processes that drive cancer cell proliferation, cell cycle progression and resistance to apoptosis in hematological malignancies and solid tumors.

Proceeds from the Series B financing will be used to advance Prelude’s proprietary PRMT5 inhibitor, PRT543, through proof of concept clinical studies. PRT543 is in a parallel dose escalation Phase 1 clinical trial for solid tumors, myeloid malignancies and lymphomas.

Series B funding will also be used to advance additional differentiated compounds from the PRMT5 program and strengthen Prelude’s discovery, preclinical and clinical development infrastructure to support a rapidly advancing pipeline beyond PRMT5. Prelude has established several drug discovery programs and compounds from these early-stage programs are also expected to enter preclinical development in the second half of 2019 with a potential IND-filing in 2020.

"We are very appreciative of the continued support of our current investors, who have been integral to the founding of Prelude and the creation of our growing pipeline," said Kris Vaddi, PhD, Founder and CEO of Prelude Therapeutics. "We believe PRMT5 inhibitors represent a promising new class of drugs to treat cancers, including ones that have developed resistance to existing targeted therapies. We are also pleased to have assembled such a talented, experienced and proven leadership team to address some of the most pressing gaps in cancer treatment."

Prelude Management Team

Dr. Vaddi founded Prelude in July 2016 and serves as CEO and a member of the Board of Directors. Prior to Prelude, Dr. Vaddi was a member of the founding team of Incyte Corporation in 2002 and most recently served as a group vice president. He initiated and championed JAK research programs at Incyte that led to the discovery, development and approval of Jakafi (ruxolotinib) for Myelofibrosis and Polycythemia Vera and Olumiant (Baricitinib) for rheumatoid arthritis. Dr. Vaddi received his Doctorate in Veterinary Medicine from APAU in India and his PhD from the University of Florida.

On May 1, 2019, David Mauro, MD, PhD, was named Chief Medical Officer. Dr. Mauro comes to Prelude with strong drug development experience in positions of increasing responsibility at Bristol-Myers Squibb, Merck and most recently Checkmate Pharmaceuticals as its Chief Medical Officer. Dr. Mauro earned his MD and PhD from Temple University School of Medicine.

Beginning July 1, 2019, Brian Piper, MBA will join Prelude as Chief Financial Officer. Mr. Piper most recently served as Chief Financial Officer at Aevi Genomic Medicine, where he was responsible for leadership and management of corporate financing and reporting, corporate fundraising efforts and investor relations. Prior to that, Mr. Piper held roles of increasing responsibility in finance, program and alliance management and investor relations at Shire Pharmaceuticals.