On December 19, 2019 Bridge Biotherapeutics Inc., a clinical stage biotech company headquartered in Seongnam, South Korea, reported that the company filed an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) and the Ministry of Food and Drug Safety (MFDS) in Korea to initiate phase I/II study of BBT-176, a clinical candidate of targeted lung cancer therapy (Press release, BridgeBio, DEC 19, 2019, View Source [SID1234552532]).

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BBT-176, a novel epidermal growth factor receptor – tyrosine kinase inhibitor (EGFR-TKI) is designed to inhibit EGFR with C797S mutations, which arise as Tagrisso (osimertinib) resistant mutations following Tagrisso treatment in non-small cell lung cancer (NSCLC). BBT-176 exhibited strong antitumor efficacy in xenograft models harboring C797S triple mutations including Del19/T790M/C797S and L858R/T790M/C797S. Furthermore, BBT-176 displayed markedly enhanced efficacy when combined with anti-EGFR antibodies.

Since the EGFR C797S mutation was reported 3 years ago, as the first evidence of Tagrisso resistance, no major breakthroughs have been achieved to target the clinically relevant mutant variant that impedes covalent bond formation with irreversible EGFR inhibitors.[i]

The company plans to initiate dose escalation studies in advanced NSCLC patients in Korea next year and to develop further clinical studies in both Korea and the US afterwards. In the Phase I/II study with NSCLC patients, the safety, tolerability and efficacy of the candidate will be observed.

"We are proud of the IND submission for BBT-176, which has shown a potential to be developed as a highly mutant-selective, fourth-generation EGFR-TKI for NSCLC treatment," stated James Lee, CEO of Bridge Biotherapeutics. "Our team will make our best effort to develop novel targeted lung cancer therapy inhibiting C797S EGFR mutation."

BBT-176 was discovered by Korea Research Institute of Chemical Technology (KRICT), a Korean government research institute, and was licensed to Bridge Biotherapeutics in December 2018 for the worldwide exclusive right for further development.

Lung cancer is the leading cause of cancer death, accounting for about one-fifth of all cancer deaths. It is split into NSCLC and small cell lung cancer (SCLC) and NSCLC accounts for approximately 85% of all lung cancers. Overall, across 8 major countries including the U.S., 5 EU countries, China and Japan, the total NSCLC population as of 2015 is assumed 2 million and the incidence of NSCLC is expected to increase at an annual growth rate of 3.1% from 2015 to 2025.[ii]

On December 19, 2019 NOXXON Pharma N.V. (Paris:ALNOX) (Euronext Growth Paris: ALNOX), a biotechnology company focused on improving cancer treatments by targeting the tumor microenvironment (TME), reported that a planned review by an independent Data Safety Monitoring Board (DSMB) has analyzed safety data from ten weeks of treatment of the first patient enrolled in the NOX-A12 plus radiotherapy brain cancer trial (Press release, NOXXON, DEC 19, 2019, View Source [SID1234552530]). Based on this assessment, the DSMB has confirmed that it is appropriate to continue the recruitment of additional patients according to the study protocol.

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The clinical trial centers participating in the study have therefore initiated the recruitment of the remaining patients in the first of three escalating dose groups. Once each patient in the first cohort has received a four-weeks treatment of NOX-A12 and radiotherapy, the DSMB will reconvene to determine whether it is safe to proceed to the middle dose level of NOX-A12.

"We are encouraged by this initial confirmation of the safety profile of NOX-A12," commented Aram Mangasarian, CEO of NOXXON. "Following this analysis, the trial can progress as planned so the next patients can receive the treatment as part of the protocol. We remain focused on reaching our goal of obtaining data from the first cohort of patients in mid-2020, and from the second and third cohorts in the fourth quarter 2020 and the second quarter of 2021, respectively."

On December 19, 2019 Cullinan Oncology, LLC reported the initiation of dosing with VK-2019, Cullinan Apollo’s first-in-class EBNA1 inhibitor for Epstein Barr Virus positive (EBV+) cancers and CLN-081, Cullinan Pearl’s novel epidermal growth factor (EGFR) tyrosine kinase inhibitor (TKI) for non-small cell lung cancer (NSCLC) (Press release, Cullinan Oncology, DEC 19, 2019, View Source [SID1234552528]). Cullinan Apollo and Cullinan Pearl are subsidiaries of Cullinan Oncology.

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VK-2019 and CLN-081 represent the first two small molecules targeting oncogenic drivers from the Cullinan Oncology pipeline. Each clinical study is a global Phase 1/2a study that utilizes an accelerated dosing schema, followed by expansion cohorts to fully characterize both safety and efficacy.

"We are grateful to our many collaborators for helping us bring these innovative medicines to patients," stated Owen Hughes, CEO of Cullinan Oncology, LLC. "We are hopeful that our medicines have the potential to positively impact the lives of those living with EBV+ nasopharyngeal carcinoma and NSCLC driven by EGFR exon 20 insertion mutations. We look forward to bringing additional targeted therapies into the clinic in the coming quarters."

About VK-2019

VK-2019 is a first-in-class EBNA1 inhibitor for EBV+ cancers. Epstein-Barr Virus (EBV) is a well-established driver of various cancers and is critically reliant on the viral DNA-binding factor EBNA1 for viral genome maintenance. In preclinical models of EBV-associated cancers, VK-2019 eliminated EBV, resulting in tumor growth inhibition. VK-2019 originated at the Wistar Institute and was licensed by Cullinan Apollo in 2018.

About CLN-081

CLN-081 (formerly TAS6417) is an orally available tyrosine kinase inhibitor designed to target activating mutations in EGFR. The molecule was engineered to inhibit EGFR variants with exon 20 insertion mutations, while sparing wild-type EGFR. CLN-081 is initially in development to target NSCLC driven by EGFR exon 20 insertion mutations. CLN-081 was developed by Taiho Pharmaceuticals and was licensed by Cullinan Pearl in 2019.

On December 19, 2019 Physicians’ Education Resource (PER), a leading resource for continuing medical education (CME), reported that it has named Scott Gottlieb, M.D., and Nalie Agustin, as the keynote speakers for the 37th Annual Miami Breast Cancer Conference (Press release, Physicians’ Education Resource, DEC 19, 2019, View Source [SID1234552527]). This year’s keynote presentations will take place at the Fontainebleau in Miami Beach, Florida.

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"We are honored to have Dr. Gottlieb and Nalie join us at this year’s legacy Miami Breast Cancer Conference," said Phil Talamo, president of PER. "Dr. Gottlieb has an incredible amount of experience in the field of health care access and public health advocacy and Nalie is such an inspirational breast cancer advocate that will provide a remarkable patient perspective to the audience."

Gottlieb is a physician and served as the 23rd commissioner of the Food and Drug Administration (FDA) from 2017-2019. His work focuses on advancing public health through developing and implementing innovative approaches to improving medical outcomes, reshaping health care delivery, and expanding consumer choice and safety. Under his leadership, the FDA advanced new frameworks for the modern and safe and effective oversight of gene therapies, cell-based regenerative medicines, targeted drugs and digital health devices. Gottlieb is widely published in leading medical journals and periodicals, including The Wall Street Journal, The New York Times and The Washington Post. Fortune magazine has recognized him as one of the "World’s 50 Greatest Leaders" in 2018 and in 2019, and he was named one of Time magazine’s "50 People Transforming Healthcare in 2018." Gottlieb will present his scientific keynote speech on Saturday, March 7 at 11:40 a.m.

Agustin is an author, speaker and wellness advocate thriving with metastatic breast cancer. She has openly chronicled her life on social media and her blog Nalie.ca since she was diagnosed with breast cancer at only 24 years old in 2013. Since then, she has amassed a large and loyal community of women seeking for hope and inspiration. Her creativity, authenticity and positive outlook have opened doors to many opportunities including being featured on Apple’s iPhone X billboards and in The American Cancer Society’s YOUnited Against Breast Cancer campaign alongside celebrities like French Montana, DJ Khaled, Kristen Chenoweth and more. She has been the Ambassador for the Canadian Breast Cancer Foundation for several years and is the spokesperson for her local hospital. Agustin is also the co-host of Thriver Talks, a podcast giving weekly tips on how to heal and live your best life beyond cancer and is currently co-authoring The Thriver’s Guide with Stephanie Seban, launching in 2020. Agustin will present her patient keynote speech on Saturday, March 7 at 11:10 a.m.

For 37 years, the Miami Breast Cancer Conference has brought together surgical, medical and radiation oncologists, as well as geneticists, pathologists, radiologists and supportive-care specialists, to foster awareness of state-of-the-art treatments for all stages and subtypes of breast cancer, provide expert perspectives on areas of clinical uncertainty or controversy, and encourage attendees to engage in cross-team cooperation in their clinics.

On December 19, 2019 UroGen Pharma Ltd. (Nasdaq: URGN) reported the U.S. Food and Drug Administration (FDA) accepted for filing and granted priority review for its New Drug Application (NDA) for UGN-101 (mitomycin gel) for instillation as a potential treatment for patients with low-grade upper tract urothelial cancer (LG UTUC) (Press release, UroGen Pharma, DEC 19, 2019, View Source [SID1234552525]). If approved, UGN-101 would be the first non-surgical treatment option for LG UTUC.

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"The FDA filing acceptance and granting of priority review for UGN-101 is an important milestone in our mission to pioneer new treatments to improve patient care in specialty cancers and urologic diseases," said Liz Barrett, President and Chief Executive Officer of UroGen. "There is a significant unmet need for a better treatment option for patients with LG UTUC, as the current standard of care involves surgical removal of the kidney or repetitive endoscopic tumor removal."

The FDA grants priority review to applications for medicines that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications. Priority review designation shortens the review period from the standard 10 months to six months from the submission of the NDA. The FDA assigned a Prescription Drug User Fee Act (PDUFA) action date of April 18, 2020.

The company is on track for the potential launch of UGN-101 by mid-year 2020. The FDA previously granted Orphan Drug, Fast Track, and Breakthrough Therapy Designations to UGN-101 for the treatment of LG UTUC.

The NDA is supported by the positive results from the pivotal Phase 3 OLYMPUS clinical trial. Results from a final analysis of the primary endpoint showed that UGN-101 demonstrated a complete response rate of 59 percent in patients with LG UTUC. In addition, the durability of response was estimated as 89 percent at six months and 84 percent at 12 months by Kaplan Meier analysis. Median time to recurrence was estimated to be 13 months. The most commonly reported treatment emergent adverse events were ureteric stenosis (43.7%), urinary tract infection (32.4%), haematuria (31.0%), flank pain (29.6%) nausea (23.9%), dysuria (21.1%), renal impairment (19.7%) and vomiting (19.7%). The majority of these adverse events were mild to moderate, with 8.5% of patients having events of ureteric stenosis reported as severe.

About The Phase 3 OLYMPUS Trial

OLYMPUS (Optimized DeLivery of Mitomycin for Primary UTUC Study) is a pivotal, open-label, single-arm Phase 3 clinical trial of UGN-101 (mitomycin gel) for instillation to evaluate the safety, tolerability and tumor ablative effect of UGN-101 in patients with low-grade UTUC. The trial enrolled 74 patients at clinical sites across the United States and Israel. Study participants were treated with six weekly instillations of UGN-101 administered via a standard catheter. Four to six weeks following the last instillation, patients underwent a Primary Disease Evaluation (PDE) to determine complete response (CR), the primary endpoint of the study. PDE involved a ureteroscopy and wash cytology, a standard microscopic test of cells obtained from the urine to detect cancer. Patients who achieved a CR at the PDE timepoint were then followed for up to 12 months to determine the durability of response with UGN-101.

About UGN-101

UGN-101 (mitomycin gel) for instillation is an investigational drug formulation of mitomycin for the treatment of low-grade upper tract urothelial cancer (LG UTUC). Utilizing the RTGel technology platform, UroGen’s proprietary sustained release, hydrogel-based formulation, UGN-101 is designed to enable longer exposure of urinary tract tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-101 is delivered to patients using standard ureteral catheters. The Company initiated its rolling submission of the UGN-101 New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in December 2018. The FDA previously granted Orphan Drug, Fast Track, and Breakthrough Therapy Designations to UGN-101 for the treatment of UTUC. If approved, UGN-101 would be the first drug approved for the treatment of LG UTUC.