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 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported the formation of the Steering Committee for its Phase 3 REGAL clinical trial of galinpepimut-S (GPS) in patients with acute myeloid leukemia (AML) who have achieved complete remission after second-line anti-leukemic therapy (CR2) (Press release, Sellas Life Sciences, APR 16, 2020, View Source [SID1234556380]).

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"We continue to make important progress toward ensuring that our Phase 3 AML trial is a well-executed pivotal study and are working diligently toward its timely execution despite the COVID-19 pandemic," said Dr. Angelos Stergiou, MD, ScD h.c., SELLAS’ President & Chief Executive Officer. "We are pleased that our internal clinical leadership team, which includes individuals with extensive late-stage hematology-oncology development experience, is now supplemented by a Steering Committee with deep and extraordinary international hematology experience."

The Steering Committee will provide scientific oversight and guidance of the practical aspects of the ongoing REGAL study. The Steering Committee will also review the results of the trial as they become available, analyze current clinical practices to identify AML patients most likely to benefit from entry to the study, design and implement the most efficient continued approaches to conducting the study and make recommendations regarding the monitoring of the clinical study in consultation with the independent data monitoring committee.

Dr. M. Yair Levy, MD, Director of Hematologic Malignancies at the Baylor University Medical Center commented, "Over the past several years, new treatment modalities have improved response rates in AML in the second line (salvage) setting, resulting in an increasing number of patients achieving complete remission (CR2). However, patients who successfully enter CR2 represent a clinical population for which there is an enduring unmet medical need, with a median overall survival of around five months. Currently, REGAL is the only Phase 3 study aiming at remission prolongation through maintenance post-CR2 therapy – other than allogeneic stem cell transplantation – that is actively enrolling patients in this setting."

"The REGAL trial is a rigorously designed study which will provide pivotal data assessing the potential contribution of maintenance therapy with galinpepimut-S, an innovatively engineered and promising WT1-targeting immunotherapeutic, in candidate AML patients in CR2. I look forward to reviewing the clinical and safety data as they become available and to serving as a member of its Steering Committee," concluded Dr. Levy.

The Steering Committee currently consists of three members:

Dr. Hagop Kantarjian, MD, Professor and Chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center, and Principal Investigator at MD Anderson for the multi-center Phase 3 REGAL study and Chair of the REGAL Steering Committee*

Dr. Javier Pinilla-Ibarz, MD, PhD, Director of Immunotherapy for Malignant Hematology at the H. Lee Moffitt Cancer Center and member of the SELLAS Scientific Advisory Board

Dr. Moshe Yair Levy, MD, Director of Hematologic Malignancies at the Texas Oncology – Baylor Charles A. Sammons Cancer Center
The Company previously reported initial data from the Phase 2a study of galinpepimut-S in AML patients in CR2 at a median follow-up of 19.3 months, showing median overall survival (OS) in vaccine-treated patients of 16.3 months vs. 5.4 months in a patient cohort contemporaneously treated with best standard therapy (p = 0.0175). The final analysis, at a median follow-up of 30.8 months, showed a median OS of 21 months in the GPS-treated patient cohort. A second previous Phase 2 study of galinpepimut-S in AML patients who achieved first complete remission (CR1) also met its primary endpoint with an OS rate at 3 years from first vaccination of 47%.

The REGAL study is an ongoing 1:1 randomized, open-label study comparing GPS monotherapy in the maintenance setting to investigators’ choice best available treatment in AML patients who have achieved hematologic complete remission, with or without thrombocytopenia (CR2/CR2p), after second-line antileukemic therapy and who are deemed ineligible for or unable to undergo allogeneic stem-cell transplantation. The primary endpoint is OS from the time of study entry. Secondary endpoints include leukemia-free survival, antigen-specific T-cell immune response dynamics, measurable residual disease by multigene array, and assessments of AML clonal evolution and inflammasome molecular signatures in the tumor microenvironment in bone marrow biopsy samples. The Company anticipates interim analysis for safety and futility in the fourth quarter of 2021.

For further information on enrolling in the REGAL study, please visit: View Source

*Dr. Kantarjian’s role on the steering committee is under review by MD Anderson’s Conflict of Interest Committee to ensure compliance with institutional policy.

On April 16, 2020 Mallinckrodt plc (NYSE: MNK), a global biopharmaceutical company, reported that it will report first quarter 2020 earnings results for the period ended March 27, 2020 on Tuesday, May 5, 2020 (Press release, Mallinckrodt, APR 16, 2020, View Source [SID1234556397]).

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A conference call for investors will begin at 8:30 a.m. Eastern Time. The call can be accessed in three ways:

At the Mallinckrodt website: http://mallinckrodt.com/investors/events-calendar/.
By telephone: For both listen-only participants and those who wish to take part in the question-and-answer portion of the call, the telephone dial-in number in the U.S. is (877) 359-9508. For participants outside the U.S., the dial-in number is (224) 357-2393. Callers will need to provide the Conference ID of 1572379.
Through an audio replay: A replay of the call will be available beginning at 11:30 a.m. Eastern Time on Tuesday, May 5, 2020, and ending at 11:59 p.m. Eastern Time on Tuesday, May 19, 2020. Dial-in numbers for U.S.-based participants are (855) 859-2056 or (800) 585-8367. Participants outside the U.S. should use the replay dial-in number of (404) 537-3406. All callers will be required to provide the Conference ID of 1572379.

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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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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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, Aeglea BioTherapeutics, Inc. (the "Company") reported that entered into a Capital on DemandTM Sales Agreement (the "Offering Agreement") with JonesTrading Institutional Services LLC, as agent ("JonesTrading"), pursuant to which the Company may offer and sell, from time to time through JonesTrading shares of the Company’s common stock, par value $0.0001 per share (the "Common Stock"), having an aggregate offering price of up to $60.0 million (the "Shares") (Filing, 8-K, Aeglea BioTherapeutics, APR 16, 2020, View Source [SID1234556381]).

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The offer and sale of the Shares will be made pursuant to a shelf registration statement on Form S-3 (File No. 333-228967) and the related base prospectus filed by the Company with the Securities and Exchange Commission (the "SEC") on December 21, 2018 as subsequently amended, and declared effective by the SEC on February 13, 2019, as supplemented by a prospectus supplement (the "Prospectus Supplement") dated April 16, 2020 and filed with the SEC pursuant to Rule 424(b) under the Securities Act of 1933, as amended (the "Securities Act").

Pursuant to the Offering Agreement, JonesTrading may sell the Shares by any method permitted by law deemed to be an "at the market offering" as defined in Rule 415 of the Securities Act (the "Offering"). JonesTrading will use commercially reasonable efforts consistent with its normal trading and sales practices to sell the Shares from time to time, based upon instructions from the Company, including any price or size limits or other customary parameters or conditions the Company may impose.

The Company is not obligated to make any sales of the Shares under the Offering Agreement. The offering of Shares pursuant to the Offering Agreement will terminate upon the earliest of (a) the sale of all the Shares subject to the Offering Agreement or (b) the termination of the Offering Agreement by JonesTrading or the Company, as permitted therein.

The Company will pay JonesTrading a commission rate up to 3.0% of the aggregate gross proceeds from each sale of Shares and have agreed to provide JonesTrading with customary indemnification and contribution rights. The Company will also reimburse JonesTrading for certain specified expenses in connection with entering into the Offering Agreement. The Offering Agreement contains customary representations and warranties and conditions to the placements of the Shares pursuant thereto.

The foregoing description of the Offering Agreement is not complete and is qualified in its entirety by reference to the full text of such agreement, a copy of which is filed herewith as Exhibit 1.1 to this Current Report on Form 8-K and is incorporated herein by reference. The opinion of the Company’s counsel regarding the validity of the Shares that will be issued pursuant to the Offering Agreement is also filed herewith as Exhibit 5.1.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the Common Stock discussed herein, nor shall there be any offer, solicitation, or sale of common stock in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.