On April 29, 2020 Fennec Pharmaceuticals Inc. (NASDAQ:FENC) (TSX:FRX), a specialty pharmaceutical company focused on the development of PEDMARKTM (a unique formulation of sodium thiosulfate) for the prevention of platinum-induced ototoxicity from cisplatin in pediatric cancer patients, reported that it intends to offer its common shares in an underwritten public offering (Press release, Fennec Pharmaceuticals, APR 29, 2020, View Source [SID1234556935]). In addition, Fennec intends to grant the underwriters a 30-day option to purchase up to an additional 15% of its common shares offered in the public offering.

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Cantor Fitzgerald & Co. is acting as the sole book-running manager for the proposed offering. Wedbush PacGrow is acting as the co-manager.

The common shares are being offered by the Company pursuant to a registration statement previously filed with and declared effective by the Securities and Exchange Commission (the "SEC"). The offering will be made only by means of a prospectus. A preliminary prospectus supplement and an accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website located at View Source Copies of the preliminary prospectus supplement and the accompanying prospectus, when filed with the SEC, may also be obtained from Cantor Fitzgerald & Co., 499 Park Avenue, 6th Floor, New York, NY 10022, Attn: Capital Markets Department, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities, in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. The securities will not be offered or sold, directly or indirectly, in Canada or to any resident of Canada.

On April 29, 2020 Seed investor CincyTech reported the formation of Kurome Therapeutics ("Kurome"), a preclinical stage company developing novel therapies targeting cancer cells’ adaptive resistance mechanisms beginning with hematopoietic, or blood cell, cancers (Press release, Kurome Therapeutics, APR 29, 2020, View Source [SID1234556932]). Kurome secured the license to develop the therapies from Cincinnati Children’s Hospital Medical Center ("Cincinnati Children’s"), a top ranked pediatric medical center and research institution.

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Kurome is developing combined IRAK1/4 and panFLT3 inhibitors to target cancer cells that evade the effects of chemotherapy drugs by adaptive resistance, having co-opted immune signaling pathways to survive. Drug resistant cancers can be deadly for many patients, and Kurome’s approach may offer a novel strategy that keeps patients in remission longer and extends overall survival. Kurome’s pipeline of IRAK 1/4, panFLT3 inhibitors have demonstrated in preclinical studies to:

Induce rapid and irrecoverable cytotoxicity in cell line models and increase overall survival in patient-derived xenograft models, well beyond that of existing clinical FLT3 inhibitors.
Synergize with and improve potency of Venclexta (Venetoclax).
Maintain complete efficacy even in settings of adaptive resistance to FLT3 inhibitors.
Kurome’s initial focus is on improving health in poor prognosis acute myeloid leukemia (AML), a deadly blood and bone marrow cancer with a high mortality rate. Kurome may potentially expand its focus to work across a range of hematopoietic cancers, including pre-leukemic conditions such as myelodysplastic syndromes (MDS). Collectively, more than 30,000 new cases of MDS and AML are diagnosed in the United States each year. The median survival time for MDS is only 2.5 years after diagnosis, and the 5-year survival rate for AML is only 27 percent.

Kurome is founded on research at Cincinnati Children’s in collaboration with the National Institutes of Health’s (NIH) National Center for Advancing Translational Sciences (NCATS).

Principal investigator and Co-Leader, Hematologic Malignancies Program at Cincinnati Children’s Cancer and Blood Diseases Institute, Daniel Starczynowski, PhD, commented, "It is a personal honor and privilege to have an impact on translating this strategy for cancer drug resistance into a therapy option against AML and cancers that act in similar ways."

CincyTech led the company’s seed investment round. "Kurome was created to accelerate the development of novel technology from world class cancer scientists at Cincinnati Children’s and NCATS. This pathway approach has the potential to add to a growing arsenal of genetically targeted cancer therapies," said John Rice, PhD, managing director of life sciences at CincyTech.

The company is being led by Jan Rosenbaum, PhD, a drug development professional, chief scientific officer and innovator with more than 25 years of pharma and biotech technical management experience. Rosenbaum is the former chief scientific officer of Airway Therapeutics, a 2011 spin-out of Cincinnati Children’s that is also a CincyTech portfolio company. She also serves as a business development advisor on the Therapeutics Development Team of the Harrington Discovery Institute.

On April 29, 2020 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biotechnology company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that clinical data on its BTK inhibitor BRUKINSA (zanubrutinib) and its anti-PD-1 antibody tislelizumab will be presented in an oral presentation and three posters at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place on May 29-31, 2020 (Press release, BeiGene, APR 29, 2020, View Source [SID1234556852]).

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Oral Presentation:

Title:

ASPEN: Results of a Phase III Randomized Trial of Zanubrutinib Versus Ibrutinib for Patients with Waldenström Macroglobulinemia (WM)

Abstract #: 8007

Session Title:
Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Lead Author:

Constantine S. Tam, MBBS, M.D., St. Vincent’s Hospital, Australia

Poster Presentations:

Title:
Three-Year Follow-up of Treatment-Naïve and Previously Treated Patients with Waldenström Macroglobulinemia (WM) Receiving Single-Agent Zanubrutinib

Abstract #: 8051

Poster #: 384

Session Title:
Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Lead Author:
Constantine S. Tam, MBBS, M.D., St. Vincent’s Hospital, Australia

Title:

Phase 3 Study of Tislelizumab Plus Chemotherapy vs Chemotherapy Alone as First line (1L) Treatment for Advanced Squamous Non-Small Cell Lung Cancer (sq NSCLC)

Abstract #: 9554

Poster #: 320

Session Title:

Lung Cancer—Non-Small Cell Metastatic Poster Session

Lead Author:

Jie Wang, M.D., Cancer Hospital Chinese Academy of Medical Sciences, China

Title:

Association Between Immune and Tumor Gene Signatures with Response or Resistance to Tislelizumab Monotherapy or in Combination with Chemotherapy in Gastroesophageal Adenocarcinoma

Abstract #: 3115

Poster #: 179

Session Title:

Developmental Therapeutics—Immunotherapy Poster Session

Lead Author
Jianming Xu, M.D., General Hospital of Chinese People’s Liberation Army, China

On April 29, 2020 Provectus (OTCQB: PVCT) reported that abstracts about and data from our clinical trials of investigational autolytic cancer immunotherapy PV-10 (rose bengal disodium) as a single-agent for the treatment of neuroendocrine tumors metastatic to the liver (NCT02693067) and in combination with immune checkpoint blockade for the treatment of uveal melanoma metastatic to the liver (NCT00986661) were accepted for the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Virtual Scientific Program, to be held May 29-31, 2020 online (Press release, Provectus Pharmaceuticals, APR 29, 2020, View Source [SID1234556851]).

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Small molecule-based PV-10 is administered by percutaneous intratumoral injection to primary or metastatic tumors of the liver, such as hepatocellular carcinoma, metastatic colorectal cancer, metastatic neuroendocrine tumors, and metastatic uveal melanoma. By targeting tumor cell lysosomes, PV-10 treatment may yield immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells.1-4

Abstract #1:

Title: Percutaneous hepatic injection of rose bengal disodium (PV-10) in metastatic uveal melanoma
Poster session: Developmental Therapeutics – Immunotherapy
Abstract number for publication: 3143
Abstract #2:

Title: Cohort 1 results of a phase I study of autolytic immunotherapy of metastatic neuroendocrine neoplasms using intralesional rose bengal disodium
Abstract number for publication: e16694
About PV-10

PV-10 is an investigational new drug 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).5,6

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.7 Cancer progression and metastasis are associated with lysosomal compartment changes8,9, which are closely correlated with (among other things) invasive growth, angiogenesis, and drug resistance10.

PV-10 selectively accumulates in the lysosomes of cancer cells upon contact, disrupting the lysosomes and causing the cells to die. Provectus1,11, external collaborators6, and other researchers13,14,16 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-10.5

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) cleavage5 and, now, stimulator of interferon genes (STING), which plays an important role in innate immunity15. 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 29, 2020, PTC Therapeutics, Inc. (the "Company"), reported that certain of the former equityholders of Agilis Biotherapeutics, Inc. ("Agilis"), and, for the limited purposes set forth in the agreement, Shareholder Representative Services LLC, entered into a Rights Exchange Agreement (the "Rights Exchange Agreement"), pursuant to which the Company agreed to issue 2,821,176 shares of its common stock (the "Common Stock Consideration") and paid $36,881,009 (the "Cash Consideration"), in the aggregate, to such former equityholders of Agilis (the "Participating Rightholders") in exchange for the cancellation and forfeiture by the Participating Rightholders of their rights to receive certain milestone-based contingent payments under the Agreement and Plan of Merger (the "Merger Agreement") by and among the Company, Agility Merger Sub, Inc., Agilis, and, solely in its capacity as the representative, agent and attorney-in-fact of the equityholders of Agilis, Shareholder Representative Services LLC, dated as of July 19, 2018, pursuant to which the Company acquired Agilis in 2018 (the "Acquisition") (Filing, 8-K, PTC Therapeutics, APR 29, 2020, View Source [SID1234556842]). Also on April 29, 2020, the Company issued 2,723,826 shares of the Common Stock Consideration to certain of the Participating Rightholders pursuant to the Rights Exchange Agreement, with the issuance of the remaining 97,350 shares of the Common Stock Consideration to certain of the Participating Rightholders who are former employees of Agilis or current or former employees of the Company to be deferred until the earlier of (i) December 15, 2020 or (ii) the date on which the Company files a registration statement on Form S-3 with respect to the resale of the shares of the Common Stock Consideration pursuant to the terms of the Rights Exchange Agreement, as further described below.
Pursuant to the terms of the Rights Exchange Agreement, the Participating Rightholders have canceled and forfeited their rights under the Merger Agreement to receive (i) $174.0 million, in the aggregate, of potential milestone payments based on the achievement of certain regulatory milestones and (ii) $37.6 million, in the aggregate, of $40.0 million in development milestone payments due upon the passing of the second anniversary of the closing of the Acquisition, regardless of whether the milestones are achieved.
The Rights Exchange Agreement has no effect on the Merger Agreement other than to provide for the cancellation and forfeiture of the Participating Rightholders’ rights to receive $211.6 million, in the aggregate, of the milestone payments described above. As a result, all other rights and obligations under the Merger Agreement remain in effect pursuant to their terms, including the Company’s obligation to pay up to an aggregate maximum amount of $22.4 million upon the achievement of certain development milestones (representing the remaining portion of potential development milestone payments after deducting the $37.6 million for which rights were canceled and forfeited pursuant to the Rights Exchange Agreement from the $40.0 million in development milestone payments that are due upon the passing of the second anniversary of the closing of the Acquisition), up to an aggregate maximum amount of $361.0 million upon the achievement of certain regulatory milestones (representing the remaining portion of potential regulatory milestone payments for which rights were not canceled and forfeited pursuant to the Rights Exchange Agreement), up to a maximum aggregate amount of $150.0 million upon the achievement of certain net sales milestones and a percentage of annual net sales for Friedreich ataxia and Angelman syndrome during specified terms, ranging from 2% to 6%, pursuant to the terms of the Merger Agreement.
Pursuant to the Rights Exchange Agreement, the Company has agreed to use commercially reasonable efforts to file as promptly as practicable after the date of the Rights Exchange Agreement, but in no event earlier than the date on which the Company files a Quarterly Report on Form 10-Q following the date of the Rights Exchange Agreement, a registration statement on Form S-3 with respect to the resale of the shares of the Common Stock Consideration issued to the Participating Rightholders pursuant to the Rights Exchange Agreement and to maintain the effectiveness of such registration statement until the six-month anniversary date of the Rights Exchange Agreement or such earlier time as all shares of the Common Stock Consideration covered by the registration statement have been sold, subject to certain exceptions and the provision of certain information by the Participating Rightholders. The Rights Exchange Agreement contains customary indemnification obligations of the Company and the former Agilis equityholders with respect to the registration statement.

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