On June 9, 2020 NFlection Therapeutics, Inc., a biopharma therapeutics developer dedicated to targeting disease pathways to uncover new approaches to fighting rare disease, reported the closing of a $20 million Series A financing round with investment from venBio Partners and F-Prime Capital (Press release, NFlection Therapeutics, JUN 9, 2020, View Source [SID1234560956]). The company also announced the initiation of the first clinical trial of its lead product, NFX-179 Gel, a topically applied therapy.

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The Phase 2a study, on the heels of the successful submission of their Investigational New Drug Application with the U.S. Food and Drug Administration, will be a safety, tolerability and pharmacokinetic/pharmacodynamic study of NFX-179 Gel in adult patients with cutaneous neurofibromatosis type-1 (NF-1). This study will evaluate three concentrations of NFX-179 Gel compared with its vehicle (placebo) in a randomized, double-blind, placebo-controlled, clinical trial of 48 patients with cutaneous neurofibromatosis type-1. The study will be conducted at five investigational centers across the United States.

"This study allows us to determine the drug’s ability to suppress key biomarkers involved in the progression of neurofibromas and will aid in the selection of doses for a larger Phase 2b study," said Christopher Powala, president & chief executive officer of NFlection. "There are no FDA-approved products for this condition, and NFX-179 Gel has the potential to address this unmet medical need."

"Almost all adults with neurofibromatosis type-1 develop cutaneous nerve tumors during their lifetime. The tumors form under the skin and manifest as nodules that can be stigmatizing and even painful," said Annette Bakker, Ph.D., President, Children’s Tumor Foundation. "We are pleased that NFlection has recognized the unmet need posed by cutaneous neurofibromas, and we are encouraged that topical NFX-179 may hopefully soon provide a life-changing solution for thousands of NF-1 patients."

About Cutaneous Neurofibromatosis Type-1
Cutaneous neurofibromas are tumors that grow from small nerves in the skin or just under the skin and appear as small or larger bumps, typically beginning around the time of puberty. It is less common to see this type of neurofibroma in young children with NF1. Individuals with NF1 commonly develop more cutaneous neurofibromas as they get older. They do not become malignant, but they may be disfiguring, itchy or painful when bumped. Despite their benign nature, cutaneous neurofibromas may cause significant problems, such as depression and a sense of isolation, and may require surgical removal.

On June 9, 2020 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) ("Jazz Pharmaceuticals") reported the pricing of $850 million aggregate principal amount of 2.000% exchangeable senior notes due 2026 in a private offering (the "offering") by Jazz Investments I Limited, its wholly-owned subsidiary (the "Issuer"), to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Jazz Pharmaceuticals, JUN 9, 2020, View Source;301072646.html [SID1234560955]). The Issuer also granted the initial purchasers of the notes a 13-day option to purchase up to an additional $150 million aggregate principal amount of notes. The sale of the notes is expected to close on June 11, 2020, subject to customary closing conditions.

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The notes will be general unsecured obligations of the Issuer and will accrue interest payable semiannually in arrears on June 15 and December 15 of each year, beginning on December 15, 2020, at a rate of 2.000% per year. The notes will mature on June 15, 2026, unless earlier exchanged, repurchased or redeemed. Prior to March 15, 2026, the notes will be exchangeable only upon satisfaction of certain conditions and during certain periods, and thereafter, at any time until the close of business on the second scheduled trading day immediately preceding the maturity date. The notes will be exchangeable for cash, ordinary shares ("ordinary shares") of Jazz Pharmaceuticals or a combination thereof, at the Issuer’s election. The initial exchange rate will be 6.4182 ordinary shares per $1,000 principal amount of notes (equivalent to an initial exchange price of approximately $155.81 per ordinary share, which represents approximately a 40.0% premium over the closing price per ordinary share on the Nasdaq Global Select Market on June 8, 2020), subject to adjustment in some events but not for any accrued and unpaid interest. The Issuer’s obligations under the notes will be fully and unconditionally guaranteed on a senior unsecured basis by Jazz Pharmaceuticals and will rank pari passu in right of payment with the Issuer’s existing 1.875% exchangeable senior notes due 2021 (the "2021 notes") and 1.500% exchangeable senior notes due 2024.

The Issuer may redeem the notes at its option, prior to June 15, 2026, in whole but not in part, in connection with certain tax-related events. The Issuer also may redeem the notes at its option on or after June 20, 2023 and prior to March 15, 2026, in whole or in part, if the last reported sale price of ordinary shares has been at least 130% of the exchange price then in effect for at least 20 trading days (whether or not consecutive) during any 30 consecutive trading day period ending within the three trading days immediately preceding the date on which the Issuer provides notice of redemption at a redemption price equal to 100% of the principal amount of the notes to be redeemed, plus accrued and unpaid interest to, but excluding, the redemption date.

If Jazz Pharmaceuticals undergoes a "fundamental change," subject to certain conditions and limited exceptions, holders of the notes may require the Issuer to repurchase for cash all or part of their notes at a repurchase price equal to 100% of the principal amount of the notes to be repurchased, plus accrued and unpaid interest to, but excluding, the fundamental change repurchase date. In addition, following certain corporate events that occur prior to the maturity date of the notes or upon the Issuer’s issuance of a notice of redemption, the Issuer will, in certain circumstances, increase the exchange rate for holders of the notes who elect to exchange their notes in connection with such a corporate event or exchange their notes called for redemption during the related redemption period, as the case may be. Jazz Pharmaceuticals estimates that the net proceeds from the offering will be approximately $833.6 million (or approximately $981.0 million if the initial purchasers exercise their option to purchase additional notes in full), after deducting the initial purchasers’ discount and commissions and estimated offering expenses payable by the Issuer. The Issuer intends to use approximately $332.9 million of the net proceeds from the offering to repurchase for cash up to approximately $332.9 million aggregate principal amount of the 2021 notes through individual privately negotiated transactions concurrently with the offering of notes. The remaining net proceeds will be used for general corporate purposes, which may include additional repurchases of 2021 notes from time to time following the offering. Note repurchases occurring concurrently with the offering of the notes, and the potential related market activities by selling holders of the 2021 notes, could increase (or reduce the size of any decrease in) the market price of the ordinary shares concurrently with the pricing of the notes, resulting in a higher effective exchange price for the notes. Note repurchases that may occur from time to time following the offering of the notes could increase (or reduce the size of any decrease in) the market price of the ordinary shares or the trading price of the notes.

None of the notes, the guarantee or the ordinary shares issuable upon exchange of the notes, if any, have been registered under the Securities Act or the securities laws of any other jurisdiction, and, unless so registered may not be offered or sold in the United States absent registration or an applicable exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and other applicable securities laws.

On June 9, 2020 Thermo Fisher Scientific reported that it has expanded its strategic partnership with Agios Pharmaceuticals by adding the co-development of a second companion diagnostic (CDx) for oncology to their existing agreement (Press release, Thermo Fisher Scientific, JUN 9, 2020, View Source [SID1234560954]). The CDx will leverage the Oncomine Precision Assay, which runs on the new Ion Torrent Genexus System, and will be used globally to identify low-grade glioma (LGG) patients with isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) mutations who may be eligible for vorasidenib (AG-881). Vorasidenib is an investigational, oral, brain-penetrant inhibitor of IDH1 and IDH2 mutations that is being developed by Agios and is currently under evaluation in the Phase 3 INDIGO study.

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Gliomas represent a broad range of primary brain tumors, ranging from highly aggressive glioblastomas to slow-growing LGG. About 11,000 new LGG patients are diagnosed in the U.S. and Europe each year, and about 80 percent have an IDH1 gene mutation. Patient symptoms range from seizures and neurologic deficits to sensory impairment and changes in behavior, with a five-year survival rate of 33 percent.

"The speed of the Genexus System in combination with the Oncomine Precision Assay has the potential to change the pace in which those diagnosed with LGG can be stratified and directed to a potentially more effective treatment in the future," said Garret Hampton, president of clinical next-generation sequencing and oncology at Thermo Fisher Scientific. "We are committed to collaborating with leading pharmaceutical partners to make precision medicine accessible to more patients everywhere."

Under the terms of the agreement, the companies will collaboratively validate the biomarkers for a test that will be based on Thermo Fisher’s Oncomine Precision Assay and used to identify variant-positive patients. Thermo Fisher will retain the rights to commercialize the test globally and will lead filings to seek clearance from the appropriate regulatory agencies.

The new agreement follows a 2017 partnership between the companies to develop and commercialize a CDx to identify patients with IDH1 mutant cholangiocarcinoma who may be eligible for TIBSOVO (ivosidenib or AG-120) as part of the ClarIDHy Phase 3 clinical study. Data from that clinical trial were presented at the 2019 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress.

The Oncomine Precision Assay is a next-generation sequencing (NGS) assay that is used to detect key biomarkers from formalin-fixed paraffin-embedded (FFPE) tissue or liquid biopsy specimen. The assay contains more than 50 cancer-related biomarkers and, when run on the Genexus System, features an automated workflow with a one-day turnaround time and the lowest sample requirements on the market for detection of both DNA and RNA variants. The latest CDx agreement is the first that leverages the Oncomine Precision Assay and the Genexus System, which were introduced to the market in November 2019.

On June 9, 2020 Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation oncology therapeutics, reported that the company will present new preclinical data for its folate receptor alpha targeting antibody-drug conjugate, STRO-002, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II being held June 22-24, 2020 (Press release, Sutro Biopharma, JUN 9, 2020, View Source [SID1234560953]).

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Additionally, Sutro’s partner Merck KGaA, Darmstadt, Germany, will be presenting preclinical data from the collaboration’s pre-Development Candidate, M1231, a first-in-class bispecific antibody-drug conjugate targeting EGFR and MUC1.

Presentation Details:

Title:

STRO-002, an anti-FolRα ADC, demonstrates immune-modulating properties and potentiates PD-L1 blockade

Abstract Number:

2250

Session Title:

Immune Mechanisms Invoked by Therapies 2

Date/Time:

June 22, 2020, 9:00 a.m. – 6:00 p.m. EDT

Presenter:

Trevor Hallam, Ph.D.

Title:

M1231: A first-in-class bispecific antibody-drug conjugate targeting EGFR and MUC1

Abstract Number:

5686

Session Title:

Emerging Mechanisms of Resistance to Targeted Therapies

Date/Time:

June 24, 2020, 10:05 a.m. – 10:15 a.m. EDT

Presenter:

Jan Anderl, Ph.D.

The abstracts can be found on the AACR (Free AACR Whitepaper) website. The Sutro virtual poster presentation will be on the AACR (Free AACR Whitepaper) website on June 22, 2020, and will be also accessible through the Clinical/Scientific Presentation and Publication Highlights page of the News section of Sutro’s website at www.sutrobio.com on the day of the poster presentation

On June 9, 2020 Menarini Silicon Biosystems, the pioneer of liquid biopsy and single cell technologies, reported that results from a new study presented at the virtual 2020 meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) suggest that circulating tumor cell (CTC) counts may be useful in determining long-term prognosis and guiding treatment selection in patients with metastatic castrate sensitive prostate cancer (mCSPC) (Press release, Menarini Silicon Biosystems, JUN 9, 2020, View Source [SID1234560952]). A second study showed predictive value of CTC counts in metastatic breast cancer. Researchers used Menarini’s CELLSEARCH Circulating Tumor Cell test,* considered the gold standard in liquid biopsy technology, to detect and count CTCs.

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A current challenge in treating mCSPC is the lack of accurate biomarkers that indicate which patients will do well with particular therapies, or how long patients will live, according to lead researcher, Amir Goldkorn, M.D., Associate Professor of Medicine at the University of Southern California’s Keck School of Medicine. With this study, researchers determined CTC counts are a non-invasive way to obtain valuable prognostic information at the start of treatment.

"These findings have important clinical implications, suggesting that patients with high initial CTC counts are less likely to respond and more likely to progress on hormonal therapy," said Dr. Goldkorn. "Though additional analysis is required, these results indicate that CTCs could become a valuable biomarker that can tell us about a patient’s long-term prognosis and help guide therapy."

The study (Abstract #5506) investigated mCSPC patients early in the disease, when participants were first being treated with hormone therapy. Researchers enumerated CTCs in 1200 men at the start of the study, and then looked at two endpoints: the level of prostate-specific antigen (PSA) after seven months, and progression-free survival (PFS) after two years.

The results showed clear prognostic value for the CTC count. The 63% of men who had no circulating tumor cells when the study began were more than six times more likely at seven months to have PSA values below 0.2, which has been shown to be highly correlated with longer survival times than higher PSA values. The men also were 3.7 times more likely to survive, with no cancer progression, after two years.

In addition to Dr. Goldkorn’s oral presentation on the study, the research was included in a live discussion among a panel of experts on the ASCO (Free ASCO Whitepaper) meeting site on Sunday, May 31.

The second study, presented as a poster at ASCO (Free ASCO Whitepaper) (Abstract #1028), examined the role of CTC counts and mutations in circulating tumor DNA (ctDNA) in predicting prognosis, treatment response and disease spread in metastatic breast cancer (MBC). Led by Massimo Cristofanilli, M.D., F.A.C.P., Associate Director for Translational Research at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, the researchers looked at 36 Stage III and 203 Stage IV breast cancer patients.

They found that CTC counts were much higher in the Stage IV patients—an average of 62.2 cells per 7.5 mL of blood compared to 14.5 cells in Stage III patients — and that within each group, high CTC counts predict worse outcomes. In addition, they discovered that mutations in one particular gene in ctDNA — known as PI3KCA — dramatically increased in Stage IV patients compared to Stage III patients, and were also highly predictive of worse prognosis and treatment outcomes.

"These new studies demonstrate the important role our rare cell technologies play in advancing precision medicine research, which could one day translate to better, more personalized treatment options for patients with prostate and breast cancer," said Fabio Piazzalunga, President and CEO of Menarini Silicon Biosystems, Inc.

CELLSEARCH is the first and only clinically validated blood test cleared by the FDA for detecting and counting CTCs to aid physicians in managing patients with metastatic breast, prostate, and colorectal cancers when used in conjunction with other clinical methods of monitoring. The test is also approved by the China Food & Drug Administration for use in monitoring patients with MBC. The CELLSEARCH System is the most extensively studied CTC technology, with research published in more than 650 peer-reviewed publications.