On October 7, 2019 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported the publication of an expert panel consensus statement that includes appropriate use criteria for DecisionDx-Melanoma in patients with cutaneous melanoma (Press release, Castle Biosciences, OCT 7, 2019, View Source [SID1234540092]). The study was published in the peer-reviewed journal SKIN: The Journal of Cutaneous Medicine.

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A panel of nine expert dermatologists, dermatologic surgeons, and dermatopathologists performed a systematic review of published evidence and developed appropriate use criteria supporting the integration of DecisionDx-Melanoma and two other validated, widely used molecular tests in melanoma patient care. The systematic review of peer-reviewed medical literature identified studies relating to clinical validity, outcomes or utility of DecisionDx-Melanoma. Employing a modified Delphi consensus technique, the panel determined the level of evidence for publications as well as an overall strength of recommendation for selected indications using standard Strength of Recommendation Taxonomy (SORT) methodology.

Key Findings

Eleven publications were identified as achieving quality levels 1 or 2, with two publications achieving the highest level of evidence (Level 1).
Eight consensus-based appropriate use criteria recommendations achieved a rating of "A" or "B", with "A" rating indicating the highest strength of recommendation.
The expert consensus-based appropriate use criteria provide an evidence-based framework to integrate the DecisionDx-Melanoma test into the management of patients with cutaneous melanoma.
"This important publication is the first to provide expert consensus-based appropriate use criteria to help clinicians integrate technologies like the DecisionDx-Melanoma test into their melanoma practice," said study co-author Darrell S. Rigel, M.D., M.S., Clinical Professor at New York University (NYU) School of Medicine. "The DecisionDx-Melanoma test has been well validated as a predictor of risk of metastasis or recurrence. The appropriate use criteria recommendations align with the current clinical use of DecisionDx-Melanoma to guide the post-diagnostic decisions to perform a sentinel lymph node biopsy surgical procedure in certain patients, and determine appropriate management plans regarding follow-up regimens, inclusion of imaging and referral to oncology."

The full published study can be accessed at the journal’s website.

On November 7, 2019 BridgeBio Pharma, Inc. (NASDAQ: BBIO) reported financial results for the third quarter, which ended September 30, 2019, and provided recent highlights across the company’s research and development portfolio (Press release, BridgeBio, NOV 7, 2019, View Source [SID1234552609]).

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"We continue to make progress towards achieving our goals, which ultimately is the delivery of meaningful medicines to patients with genetic diseases," said Neil Kumar, Ph.D., founder and chief executive officer of BridgeBio. "We will present new data from our TTR stabilizer program this month at the American Heart Association (AHA). We are also on track to begin filing this year our rolling new drug application for BBP-870, a treatment for the often-fatal genetic disease molybdenum cofactor deficiency type A. We are growing our pipeline as well, adding BBP-418, a novel treatment for the neuromuscular disorder limb-girdle muscular dystrophy type 2i. We remain on track to put five or more programs into the clinic next year on a risk-adjusted basis."

Recent Highlights:

BBP-831 – FGFR1-3 inhibitor for achondroplasia: Initiated PROPEL, a prospective observational study in children with achondroplasia, the most common genetic form of short stature (NCT04035811). The study will establish annualized growth velocity (AGV) for each child over a minimum period of six months. PROPEL is designed to provide baseline measurements for children who enroll in PROPEL2, a Phase 2 study of low-dose infigratinib in achondroplasia which is on track to start in 2020. Additionally, in October 2019, new preclinical data supporting tolerability and efficacy of infigratinib in the mouse model of achondroplasia were reported at the American Society of Human Genetics conference (link to poster).

BBP-870 – cPMP replacement therapy for MoCD type A: Presented natural history study data at the Society of Inborn Errors of Metabolism Conference (link to poster) in September. These data suggest an urgent need for new therapies in molybdenum cofactor deficiency (MoCD) type A, an often-fatal rare genetic disease, and will be a critical component of the planned new drug application.

BBP-812 – Gene therapy candidate for Canavan disease: Opened a natural history study in Canavan disease (treatcanavan.com). Presented preclinical data (link to poster) demonstrating intravenous (IV) dosing of BridgeBio’s experimental therapy for Canavan disease (BBP-812) achieved broad central nervous system delivery; the IV approach is much less invasive compared to intrathecal or intracerebroventricular alternatives.

BBP-631 Gene therapy candidate for CAH: Presented preclinical update (link to poster) for gene therapy candidate BBP-631 in congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency wherein IV dosing of non-human primates with BBP-631 resulted in durable delivery and expression of the gene product to the adrenal tissue.

BBP-398 – SHP2 inhibitor for treatment-resistant cancer: Presented data (link to poster) highlighting the discovery and preclinical efficacy of BBP-398, a potent and selective SHP2 inhibitor, which is currently being prepared for the submission of an IND in 2020 for evaluation in RTK-driven cancer.

BBP-265 (AG10) – TTR stabilizer for ATTR: Granted Alexion Pharmaceuticals, Inc. an exclusive license to develop and commercialize AG10 in Japan for an upfront payment of $25 million and an equity investment of $25 million.

Pipeline growth: Announced addition of a new asset, BBP-418, to the pipeline. BBP-418 is a substrate supplementation therapy for the treatment of limb-girdle muscular dystrophy type 2i and is in IND-enabling studies. This condition affects an estimated 7,000 patients in the United States and European Union with no currently approved therapies.

Organizational growth: Added two new members to the senior leadership team. Brian Stolz joined as Chief Operating Officer of BridgeBio. Mr. Stolz most recently held the position of Chief People Officer at Activision Blizzard. Yi Ching Yau joined as Chief Accounting Officer of BridgeBio. Prior to joining BridgeBio, Ms. Yau served as the VP of Finance at Nektar Therapeutics.

Upcoming Milestones:

BBP-265 (AG10) – TTR stabilizer for ATTR: Plan to present interim analysis of the ongoing Phase 2 open label extension study (NCT03536767) of AG10 in patients with TTR amyloid cardiomyopathy, an inherited form of heart failure, at the American Heart Association 2019 Scientific Sessions in a Late-Breaking Featured Science Oral Presentation. A Phase 3 study of AG10 in ATTR-PN (ATTRibute-PN) is on track to begin in the first quarter of 2020.

BBP-870 – cPMP replacement therapy for MoCD type A: On track to initiate a rolling new drug application submission for our first-in-class therapy for molybdenum cofactor deficiency (MoCD) type A, BBP-870, by the end of 2019.

BBP-589 – COL7A protein replacement therapy for recessive dystrophic epidermolysis bullosa: Plan to share topline data from the ongoing Phase 1/2 study (NCT03752905) during 2020.

BBP-831 (infigratinib) – FGFR1-3 inhibitor for FGFR2+ cholangiocarcinoma: Plan to complete enrollment of the ongoing pivotal Phase 2 study (NCT02150967) in second line cholangiocarcinoma (bile duct cancer) and present updated results at a major oncology meeting in 2020. Remain on track to submit new drug application for FDA approval in 2020.

Consolidated cash, cash equivalents and marketable securities, excluding restricted cash, totaled $611.9 million as of September 30, 2019. Excluding Eidos, BridgeBio’s cash balance as of September 30, 2019 was $446.1 million compared to $162.4 million as of June 30, 2019. The net change in cash balance of $283.7 million reflects net proceeds received from BridgeBio’s initial public offering of $368.7 million, offset by the repurchase of a non-controlling interest for $26.4 million and approximately $58.6 million primarily for operating expenses.

Operating Expenses

Operating expenses for the three months that ended September 30, 2019 were $81.3 million, as compared to $41.5 million for the same period in the prior year. The increase in operating expenses of approximately $39.8 million was mainly attributable to increased research and development expenses related to the progression of our programs

On October 7, 2019 Context Therapeutics, a clinical-stage biopharmaceutical company dedicated to advancing treatments for hormone driven cancers, reported a Phase 2 clinical collaboration with the Wisconsin Oncology Network (Press release, Context Therapeutics, OCT 7, 2019, View Source [SID1234540077]). This clinical collaboration will evaluate whether the addition of Apristor to the antiestrogen, fulvestrant, can enhance outcomes for patients with metastatic breast cancer whose cancer has progressed on prior therapies.

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The Phase 2 trial will assess the combination of the progesterone receptor antagonist, Apristor (onapristone ER) plus the antiestrogen, Faslodex (fulvestrant), in up to 40 patients who have ER+,PR+, and HER2- tumors and who have received prior antiestrogen (aromatase inhibitor) plus CDK4/6 inhibitor treatment. The primary endpoint will be overall response rate (ORR), which is the proportion of patients who have either a complete or partial response. To further characterize the activity of Apristor, secondary endpoints will include duration of response, clinical benefit rate, and progression-free survival (PFS). In addition, this study will evaluate the safety and pharmacological profile of the combination in these patients, as well as biomarker and functional imaging analyses to explore predictive factors of response to complete hormone blockade. This data will support Context’s ongoing Phase 2 studies and help design a future Phase 3 trial.

20191007 WON Announcement.jpg
"Currently, there are limited therapeutic options to treat hormone driven breast cancer in the advanced setting. Recent preclinical findings in models of antiestrogen and/or CDK4/6 inhibitor resistance give us reason to believe that Apristor when combined with an antiestrogen can provide complete hormone blockade and help women with ER+,PR+,HER2- breast cancers," said Martin Lehr, CEO of Context Therapeutics. "We are humbled by the enthusiasm and support of Wisconsin Oncology Network (WON), coordinated out of the University of Wisconsin Carbone Cancer center, a leading breast cancer clinical consortium in the Midwest. The skill and scale of WON, under the leadership of Drs. Ruth O’Regan, Ryan Mattison, and Kari Wisinski, gives our company tremendous confidence that WON will maximize patient access to this important trial."

The study will be coordinated by the Study Chair, Dr. Sailaja Kamaraju, an Associate Professor of Medical Oncology at the Medical College of Wisconsin, and study’s Primary Investigator, Dr. Kari Wisinski, Associate Professor of Medical Oncology at the University of Wisconsin Carbone Cancer Center. Final study design and other details will be announced upon enrollment of the first patient, expected in early 2020.

"The majority of breast cancer patients have hormone driven breast cancer. The hormones estrogen and progesterone drive breast cancer progression in those patients, but antiestrogens are the only antihormonal therapy available to clinicians. Therefore, treatment of those patients to date has consisted of antiestrogens alone or in combination with agents, including CDK4/6 inhibitors, that enhance the antitumor activity of antiestrogens. Given the broad use of antiestrogens, antiestrogen resistance is now a major clinical challenge," said Dr. Kamaraju. "We believe that a progesterone receptor antagonist has the potential to address antiestrogen resistance, which we believe will lead to better outcomes for patients. This study, run in parallel with other Apristor breast cancer studies, including a window of opportunity (neoadjuvant) study at SOLTI and a first line (1L) biochemical recurrence study at Memorial Sloan Kettering Cancer Center, will provide clinicians with a complete picture of how Apristor works in advanced ER+,PR+,HER2- breast cancer and inform the design of a future Phase 3 trial."

About Hormone Driven Breast Cancer
Hormone receptor positive (HR+) breast cancer is the most common form of breast cancer and accounts for more than 70% of all breast cancers. Metastatic HR+ cancer is usually treated with antiestrogen therapies first that help stop tumor growth. For many patients, antiestrogen therapy becomes ineffective over time and the cancer becomes resistant to antiestrogen therapy. In this recurrent setting, progesterone receptor has emerged as a prominent resistance mechanism. It is estimated that there are over 750,000 patients with recurrent disease worldwide.

On October 7, 2019 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, reported that the Company will release third quarter 2019 financial results after the close of trading on Monday, November 4, 2019 (Press release, NanoString Technologies, OCT 7, 2019, View Source [SID1234540093]). Company management will host a conference call beginning at 4:30pm ET to discuss those results and provide a business update.

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Individuals interested in listening to the conference call may do so by dialing (866) 211-0364 for domestic callers, or (647) 689-6861 for international callers. Please reference Conference ID: 9358402. To listen to a live webcast, please visit the investor relations section of the company’s website at nanostring.com.

A replay of the call will be available beginning November 4, 2019 at 7:30pm ET through midnight on November 11, 2019. To access the replay, dial (800) 585-8367 or (416) 621-4642 and reference Conference ID: 9358402. The webcast will also be available on the Company’s website for one year following the completion of the call.

On October 4, 2019 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported a publication from The University of Texas, MD Anderson Cancer Center entitled, "Pan-Cancer Landscape and Functional Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity (Press release, Spectrum Pharmaceuticals, OCT 4, 2019, View Source [SID1234540055])." The publication appears in the Oct 3, 2019 online issue at View Source(19)30384-8 and will be published in a future print issue of Cancer Cell.

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"Our analysis is the largest ever conducted to understand the diversity of HER2 mutations across 25 cancer types, including more than 200,000 patients from cBioPortal, MD Anderson, Foundation Medicine, and Guardant Health," said John Heymach, M.D., Ph.D., Chairman and Professor, Department of Thoracic/Head and Neck Medical Oncology at MD Anderson. "In our pre-clinical study of 11 EGFR/HER2 tyrosine kinase inhibitors, poziotinib was the most potent HER2 mutant-selective TKI tested, and in our initial clinical cohort we found that poziotinib was highly active in NSCLC patients with HER2 exon 20 mutations. Our findings indicate that poziotinib may be well-suited to target HER2 mutations with a constricted binding pocket. Furthermore, we have determined from pre-clinical data that poziotinib is synergistic with a HER2-targeting antibody-drug conjugate, providing a rationale for combinations to move forward into the clinic."

Spectrum is studying poziotinib in ZENITH20, a company-sponsored, open-label, single-arm, multi-center, global Phase 2 study of non-small cell lung cancer (NSCLC) patients.

"The publication of these latest research findings from MD Anderson on poziotinib in the journal Cancer Cell continues to strengthen the evidence of the potential benefit of poziotinib in the treatment of lung cancer," said Joe Turgeon, President and CEO, Spectrum Pharmaceuticals. "This quarter, we plan to disclose topline data from the first cohort of the company-sponsored ZENITH20 study, which is analyzing previously-treated NSCLC patients with exon 20 mutations in EGFR. By mid-2020 we also expect topline data from cohort 2, which is studying previously treated NSCLC patients with exon 20 mutations in HER2. We look forward to the top line data from the ZENITH20 study this quarter and continue to expand the poziotinib program, based on emerging science, to other areas of opportunity."

About Poziotinib

Poziotinib is a novel, oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that inhibits the tyrosine kinase activity of EGFR (HER1) as well as HER2 and HER4. Importantly this leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer.

Spectrum received exclusive license from Hanmi Pharmaceuticals to develop, manufacture, and commercialize poziotinib worldwide, excluding Korea and China. Poziotinib is currently being investigated by Spectrum and Hanmi in several trials in multiple solid tumors.

About ZENITH20

The ZENITH20 study consists of seven cohorts of NSCLC patients. Cohorts 1 (EGFR) and 2 (HER2) have completed enrollment of previously-treated NSCLC patients with exon 20 mutations. Cohort 3 (EGFR) and 4 (HER2) are currently enrolling first-line NSCLC patients with exon 20 mutations. Cohorts 1- 4 are each independently powered for a pre-specified statistical hypothesis and the primary endpoint is objective response rate (ORR). In July 2019, three new cohorts were added to the ZENITH20 study that are all currently enrolling patients. Cohort 5 includes previously treated or treatment-naïve NSCLC patients with EGFR or HER2 exon 20 insertion mutations. Cohort 6 includes NSCLC patients with classical EGFR mutations who progressed while on treatment with first-line osimertinib and developed an additional EGFR mutation. Cohort 7 includes NSCLC patients with a variety of less common mutations in EGFR or HER2 exons 18-21 or the extracellular or transmembrane domains.