On April 16, 2020 Foundation Medicine, Inc. reported that the U.S. Food and Drug Administration (FDA) approved FoundationOneCDx as the registrational companion diagnostic for Incyte’s Pemazyre (pemigatinib), a selective fibroblast growth factor receptor (FGFR) inhibitor approved for adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test (Press release, Foundation Medicine, APR 16, 2020, View Source [SID1234556420]). FoundationOne CDx is the first and only FDA-approved companion diagnostic test for this indication.

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Cholangiocarcinoma is a rare cancer, diagnosed in approximately 8,000 patients annually, according to the American Cancer Society. It is classified based on its origin: intrahepatic cholangiocarcinoma (iCCA) occurs in the bile duct inside the liver and extrahepatic cholangiocarcinoma occurs in the bile duct outside the liver. FGFR2 fusions or select rearrangements occur in 10-16 percent of iCCA patients.1, 2, 3 Because this cancer is difficult to detect, patients with cholangiocarcinoma are often diagnosed at a late or advanced stage when the prognosis is poor and treatment options are limited.4 The approval of this novel therapy and companion diagnostic means healthcare professionals will be able to use Foundation Medicine’s comprehensive genomic profiling (CGP) assay, FoundationOne CDx, to identify patients with FGFR2 fusions and select rearrangements who may benefit from treatment with Pemazyre in accordance with the approved therapeutic product labeling.

"The approval of this therapy and companion diagnostic is an important step forward in advancing care for patients with cholangiocarcinoma for whom there are limited treatment options," said Brian Alexander, M.D., M.P.H., chief medical officer at Foundation Medicine. "The breadth and depth of our sequencing allows for identification of patients with this rare fusion who may benefit from Pemazyre, underscoring the importance of comprehensive genomic profiling in cholangiocarcinoma. We continue to work toward broadening patient access to biomarker-driven therapies, illustrated by this recent milestone. We are proud to add another important FDA-approved companion diagnostic to FoundationOne CDx."

FoundationOne CDx is the first FDA-approved broad companion diagnostic that is clinically and analytically validated for solid tumors. It is currently approved as the companion diagnostic test for 20 unique therapies across multiple cancer types.

"Patients with rare cancers like cholangiocarcinoma often face additional challenges when it comes to available research and treatment options for their condition," said Jim Palma, Executive Director at Target Cancer Foundation. "The approval of this therapy and companion diagnostic is a turning point for these patients and the rare cancer community as a whole. Not only could it be lifechanging for cholangiocarcinoma patients with FGFR2 fusions and select rearrangements, but it reinforces the critical need for comprehensive genomic profiling and the power of collaboration among scientists, clinicians, patients and advocacy organizations."

Incyte announced earlier today the U.S. FDA approval of Pemazyre as the first selective FGFR inhibitor for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement as detected by an FDA-approved test. Pemazyre is a potent, selective, oral inhibitor of FGFR isoforms 1, 2 and 3 which, in preclinical studies, has demonstrated selective pharmacologic activity against cancer cells with FGFR alterations. More information about Pemazyre can be found at www.pemazyre.com.

About FoundationOne CDx

FoundationOne CDx is a next-generation sequencing based in vitro diagnostic device for detection of substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed paraffin embedded (FFPE) tumor tissue specimens. FoundationOne CDx is intended as a companion diagnostic to identify patients who may benefit from treatment with certain targeted therapies in accordance with their approved therapeutic product labeling. Additionally, FoundationOne CDx is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology for patients with solid malignant neoplasms. For a full list of targeted therapies for which FoundationOne CDx is indicated as a companion diagnostic, please visit View Source

About FGFR

Fibroblast growth factor receptors (FGFRs) play an important role in tumor cell proliferation and survival, migration and angiogenesis (the formation of new blood vessels). Activating fusions, rearrangements, translocations and gene amplifications in FGFRs are closely correlated with the development of various cancers.

On April 16, 2020 Provectus (OTCQB: PVCT) reported that data from its clinical trial of autolytic cancer immunotherapy PV-10 (rose bengal disodium) as a single-agent and in combination with immune checkpoint blockade for the treatment of primary or metastatic tumors of the liver (NCT00986661) was uploaded to the SIR 2020 ePoster Gallery of the canceled Society of Interventional Radiology (SIR) 2020 Annual Scientific Meeting, which was originally scheduled to be held March 28-April 2, 2020 in Seattle, Washington (Press release, Provectus Pharmaceuticals, APR 16, 2020, View Source [SID1234556419]).

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SARS-CoV-21 note: Provectus’ ongoing clinical trials continue to enroll new patients, and patients who have been enrolled and treated on these trials still receive care.

Small molecule-based PV-10 is administered by percutaneous intratumoral injection to primary or metastatic tumors of the liver, such as hepatocellular carcinoma (HCC), metastatic colorectal cancer (mCRC), metastatic neuroendocrine tumors, and metastatic uveal melanoma (mUM). Intratumoral injection with lysosomal-targeting PV-10 yields immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells.2-5

This multicenter, open-label, Phase 1 basket study is evaluating PV-10’s safety, tolerability, and preliminary efficacy in unresectable cancers of the liver. PV-10 is administered under image guidance to one to three tumors of 1.0 to 4.9 cm in diameter. Response assessments (Computed Tomography [CT], Magnetic Resonance Imaging [MRI], and/or Positron Emission Tomography [PET]) are performed at day 28, and then every 12 weeks. Patients with additional injectable disease may receive further PV-10 injection after day 28. Modified Response Evaluation Criteria in Solid Tumors (mRECIST) and European Association of the Study of the Liver (2D-EASL) criteria were used to evaluate response of injected tumors; 2D-EASL response assessment measures only viable tumor tissue. PV-10 is radiopaque, which facilitates disease treatment and response follow-up.

Updated Hepatic Tumor Results from the Presentation at SIR 2020:

Baseline characteristics (N=32): 44% male; median age of 66 years (range 32-89).
Disease characteristics: HCC (7 patients), mCRC (6), mUM (13); other metastases included lung carcinoma (2), cutaneous melanoma (1), breast carcinoma (1), ovarian adenocarcinoma (1), and pancreatobiliary adenocarcinoma (1)
Safety summary: Treatment-emergent serious adverse events attributed to PV-10 were observed in 6 patients (5 patients experienced transient CTCAE Grade 3 events that resolved with sequalae; 1 patient experienced Grade 5 thrombus)
Treatment summary: 49 injected tumors (46 interventional procedures); 1 tumor injected twice
Tumor treatment patterns, response characteristics, and patient status:
HCC: 10 evaluable injected lesions by mRECIST, 30% object response rate (ORR), 90% disease control rate (DRR); 8 evaluable by 2D-EASL, 75% ORR, 100% DCR; 4 of 7 patients alive (range 0-112 months)
mCRC: 6 evaluable injected lesions by mRECIST, 67% DCR; ; 5 evaluable by 2D-EASL, 60% ORR, 60% DCR; 2 of 6 patients alive (3-97+ months)
mUM: 10 of 13 patients alive (4.6-22.7 months)
Patient survival characteristics:
HCC: median overall survival (OS) and disease-specific survival (DSS) not reached
mCRC: median 26.8 months OS and DSS (range 3-97+)
mUM: median OS and DSS not reached; initial follow-up <24 months
Dominic Rodrigues, Vice Chair of the Company’s Board of Directors, said, "These single-agent PV-10 and combination therapy data further support our drug development strategy and specific plans of developing a registrational study of the combination of PV-10, ipilimumab, and nivolumab for the treatment of uveal melanoma metastatic to the liver as well as a Phase 2 study of the combination of PV-10 and an anti-PD-(L)1 agent for first- and/or second-line treatment of hepatocellular carcinoma."

A copy of our poster presentation is available on Provectus’ website at View Source

On March 4th, SIR and SIR Foundation leadership cancelled the SIR 2020 Annual Scientific Meeting. SIR asked all presenters to upload their presentations to the SIR 2020 ePoster Portal.

About PV-10

PV-10 is undergoing clinical study for adult solid tumor cancers, like melanoma and cancers of the liver (including metastatic neuroendocrine tumors and metastatic uveal melanoma). PV-10 is also undergoing preclinical study for pediatric solid tumor cancers (like neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma) and pediatric blood cancers (like leukemia).6,7

Tumor Cell Lysosomes as the Seminal Drug Target

Lysosomes are the central organelles for intracellular degradation of biological materials, and nearly all types of eukaryotic cells have them. Discovered by Christian de Duve, MD in 1955, lysosomes are linked to several biological processes, including cell death and immune response. In 1959, de Duve described them as ‘suicide bags’ because their rupture causes cell death and tissue autolysis. He was awarded the Nobel Prize in 1974 for discovering and characterizing lysosomes, which are also linked to each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Building on the Discovery, Exploration, and Characterization of Lysosomes

Cancer cells, particularly advanced cancer cells, are very dependent on effective lysosomal functioning.8 Cancer progression and metastasis are associated with lysosomal compartment changes9,10, which are closely correlated with (among other things) invasive growth, angiogenesis, and drug resistance11.

PV-10 selectively accumulates in the lysosomes of cancer cells upon contact, disrupting the lysosomes and causing the cell to die. Provectus2,12, external collaborators6, and other researchers13-15 have independently shown that PV-10 (RB) triggers each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Cancer Cell Autolytic Death via PV-10: PV-10 induced autolytic cell death, or death by self-digestion, in Hepa1-6 murine HCC cells can be viewed in this Provectus video of the event (ethidium homodimer 1 [ED-1] stains DNA, but is excluded from intact nuclei; lysosensor green [LSG] stains intact lysosomes; the video is provided in 30-second frames; the event has a duration of approximately one hour). Exposure to PV-10 triggers the disruption of lysosomes, followed by nucleus failure and autolytic cell death. Identical responses have been shown by the Company in HTB-133 human breast carcinoma (which can be viewed in this Provectus video; this event has a duration of approximately two hours) and H69Ar human multidrug-resistant small cell lung carcinoma. Cancer cell autolytic cell death was reproduced by research collaborators from POETIC using relapsed and refractory human pediatric neuroblastoma cells to show that lysosomes are disrupted upon exposure to PV-10.6

Immune Signaling Pathways: PV-10 causes acute autolytic destruction of injected tumors (i.e., cell death), mediating several identified immune signaling pathways studied to date, such as the release of danger-associated molecular pattern molecules (DAMPs) and tumor antigens that initiate an immunologic cascade where local response by the innate immune system facilitates systemic anti-tumor immunity by the adaptive immune system. The DAMP release-mediated adaptive immune response activates lymphocytes, including CD8+ T cells, CD4+ T cells, and NKT cells, based on clinical and preclinical experience in multiple tumor types. Other mediated immune signaling pathways that have been identified include poly-ADP ribose polymerase (PARP) cleavage and, now, stimulator of interferon genes (STING), which plays an important role in innate immunity. PV-10 is the first cancer drug that may facilitate multiple, complementary, immune system signaling pathways.16

Orphan Drug Designations (ODDs)

ODD status has been granted to PV-10 by the U.S. Food and Drug Administration for the treatments of metastatic melanoma in 2006, hepatocellular carcinoma in 2011, neuroblastoma in 2018, and ocular melanoma (including uveal melanoma) in 2019.

Drug Product

Rose bengal disodium (RB) (4,5,6,7-tetrachloro-2’,4’,5’,7’-tetraiodofluorescein disodium salt) is a small molecule halogenated xanthene and PV-10’s active pharmaceutical ingredient. PV-10 drug product is a formulation of 10% w/v RB in 0.9% saline, supplied in single-use glass vials containing 5 mL (to deliver) of solution, and administered without dilution to solid tumors via intratumoral injection.

Intellectual Property (IP)

Provectus’ IP includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the process by which pharmaceutical grade RB and related halogenated xanthenes are produced, reducing the formation of previously unknown impurities that exist in commercial grade RB in uncontrolled amounts. The requirement to control these impurities is in accordance with International Council on Harmonisation (ICH) guidelines for the manufacturing of an injectable pharmaceutical. US patent numbers are 8,530,675, 9,273,022, and 9,422,260, with expirations ranging from 2030 to 2031.

The Company’s IP also includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the combination of PV-10 and systemic immunomodulatory therapy (e.g., anti-CTLA-4, anti-PD-1, and anti-PD-L1 agents) for the treatment of a range of solid tumor cancers. US patent numbers are 9,107,887, 9,808,524, 9,839,688, and 10,471,144, with expirations ranging from 2032 to 2035.

On April 16, 2020 Gilead Sciences, Inc. (Nasdaq: GILD) reported that its first quarter 2020 financial results will be released on Thursday, April 30, after the market closes (Press release, Gilead Sciences, APR 16, 2020, View Source [SID1234556418]). At 4:30 p.m. Eastern Time, Gilead’s management will host a conference call to discuss the company’s first quarter 2020 financial results and will provide a business update.

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The live webcast of the call can be accessed at the company’s Investors page at View Source Please connect to the company’s website at least 15 minutes prior to the start of the call to ensure adequate time for any software download that may be required to listen to the webcast. Alternatively, please call 877-359-9508 (U.S.) or 224-357-2393 (international) and dial the conference ID 1898512 to access the call. Telephone replay will be available approximately two hours after the call through 11:59 p.m. Eastern Time, May 2, 2020. To access the replay, please call 855-859-2056 (U.S.) or 404-537-3406 (international) and dial the conference ID 1898512. The webcast will be archived on www.gilead.com for one year.

On April 16, 2020 Beijing Mabworks Biotech reported that it raised $160 million in a Series C1/C2 funding to support its biologic drug development efforts (Press release, Mabworks Biotech, APR 16, 2020, View Source [SID1234556410]). Founded in 2011, Mabworks has more than 15 candidates being tested in China and US trials targeting diseases that include lung, breast and colorectal cancers, leukemia and infectious diseases. The company has partnered with InnoCare Pharma to develop a novel therapy for B-cell lymphoma, and it also collaborates with China’s Betta Pharma, an oncology company. The funding was led by CICC Qide Innovative Biopharma Equity Investment Fund, CITIC Securities, Lyzz Capital and Huge Capital.

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On April 16, 2020, INmune Bio Inc. (the "Company") reported that it entered into an At-The-Market Sales Agreement (the "Sales Agreement") with BTIG, LLC ("BTIG"), pursuant to which the Company may offer and sell, from time to time, through BTIG, as sales agent, shares of its common stock, par value $0.001 per share (the "Common Stock"), having an aggregate offering price of up to $10,000,000, subject to certain limitations on the amount of Common Stock that may be offered and sold by the Company set forth in the Sales Agreement (Filing, 8-K, INmune Bio, APR 16, 2020, View Source [SID1234556409]). The Company is not obligated to make any sales of Common Stock under the Sales Agreement and any determination by the Company to do so will be dependent, among other things, on market conditions and the Company’s capital raising needs.

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Offers and sales of Common Stock by the Company under the Sales Agreement, if any, will be made through a prospectus supplement to the prospectus forming a part of the Company’s shelf registration statement on Form S-3 (File No. 333-237638) declared effective by the Securities and Exchange Commission (the "SEC") on April 2, 2020 (the "Registration Statement"). The Company filed with the SEC a prospectus supplement dated April 16, 2020 specifically relating to offers and sales of Common Stock under the Sales Agreement (the "ATM Prospectus Supplement"), together with the prospectus forming a part of the effective registration statement. Due to the offering limitations currently applicable to the Company under General Instruction I.B.6. of Form S-3 and the Company’s public float as of as of April 16, 2020, and in accordance with the terms of the Sales Agreement, the Company may offer and sell shares of Common Stock having an aggregate gross sales price of up to $6,678,000 (the "Shares") under the ATM Prospectus Supplement through BTIG, as sales agent, pursuant to the Sales Agreement. If the Company’s public float increases after the date of the ATM Prospectus Supplement such that the Company may sell additional amounts of Common Stock under the Sales Agreement and the Registration Statement, the Company will file with the SEC another prospectus supplement to the prospectus forming a part of the Registration Statement that will include such additional amount of shares of Common Stock that the Company may sell under the Sales Agreement before any such additional shares are sold under the Sales Agreement.

Shares may be sold through the ATM Prospectus Supplement by any method deemed to be an "at the market offering" as defined in Rule 415(a)(4) under the Securities Act of 1933, as amended. including sales made through The Nasdaq Capital Market or any other trading market for the common stock, sales made to or through a market maker other than on an exchange or through an electronic communications network, or in negotiated transactions pursuant to terms set forth in a placement notice delivered by the Company to BTIG under the Sales Agreement. Upon delivery of a placement notice and subject to the terms and conditions of the Sales Agreement, BTIG will use commercially reasonable efforts, consistent with its normal trading and sales practices, applicable state and federal law, rules and regulations, and the rules of The Nasdaq Capital Market, to sell the Shares from time to time based upon the Company’s instructions, including any price, time or size limits specified by the Company. BTIG is not obligated to purchase any shares of Common Stock on a principal basis pursuant to the Sales Agreement.

The Company will pay BTIG commissions for its services in acting as agent in the sale of shares of Common Stock pursuant to the Sales Agreement. BTIG will be entitled to compensation at a fixed commission rate of 3.0% of the gross proceeds from the sale of shares of Common Stock pursuant to the Sales Agreement. The Company has agreed to provide BTIG with customary indemnification and contribution rights, including for liabilities under the Securities Act. The Company also will reimburse BTIG for certain specified expenses in connection with entering into the Sales Agreement. The Sales Agreement contains customary representations and warranties and conditions to the placements of the Shares pursuant thereto. The Sales Agreement will terminate upon the earlier of (i) the sale of all shares of Common Stock subject to the Sales Agreement and (ii) termination of the Sales Agreement as permitted therein. The Company may terminate the Sales Agreement in its sole discretion at any time by giving 10 days’ prior notice to BTIG. BTIG may terminate the Sales Agreement under the circumstances specified in the Sales Agreement and in its sole discretion at any time by giving 10 days’ prior notice to the Company.