January 2020 – Page 59 – 1stOncology™: Cancer Intelligence Service

Chi-Med Announces Proposed Public Offering of ADSs

On January 21, 2020 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) reported that it intends to offer US$110 million of American Depositary Shares ("ADSs"), each representing five ordinary shares, par value US$0.10 each of Chi-Med, on the Nasdaq Global Select Market ("Offering") (Press release, Hutchison China MediTech, JAN 21, 2020, https://www.chi-med.com/chi-med-announces-proposed-public-offering-of-adss/ [SID1234553364]). Chi-Med intends to grant the underwriters a 30-day option to purchase up to an aggregate of US$16.5 million of additional ADSs at the public offering price, less underwriting discounts and commissions. The Offering is subject to market and other conditions, and there can be no assurance as to whether or when the Offering may be completed, or as to the actual size or final terms of the Offering. The price for the Offering has not yet been determined.

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Chi-Med will receive all of the net proceeds from the sale of ADSs in the Offering, if completed, which it intends to use primarily to fund its ongoing research and clinical development efforts and expand its commercialization capabilities.

Details of the final terms of the Offering will be determined following the bookbuilding process.

BofA Securities, Inc., Goldman Sachs (Asia) L.L.C. and Morgan Stanley & Co. LLC (in alphabetical order) are acting as joint global coordinators and joint bookrunners for the Offering.

Chi-Med’s directors intend that the Offering would be effected within existing allotment authorities and pre-emption disapplications granted pursuant to shareholder resolutions passed at Chi-Med’s annual general meeting held on April 24, 2019. The Offering would therefore not be conditional upon shareholder approval.

Shareholders and potential investors should note that the proposed Offering may or may not proceed and are accordingly advised to exercise caution when dealing in the securities of Chi-Med.

Heat Biologics, Inc. Announces Closing of $7,000,000 Public Offering

On January 21, 2020 Heat Biologics, Inc. ("Heat") (NASDAQ:HTBX), a clinical-stage biopharmaceutical company specializing in the development of therapeutics designed to activate patients’ immune systems against cancer, reported the closing of its previously announced underwritten public offering consisting of 20,000,000 shares of Common Stock together with Warrants to purchase 10,000,000 shares of Common Stock at a combined price to the public of $0.35 (Press release, Heat Biologics, JAN 21, 2020, View Source [SID1234553363]). The gross proceeds to the Company from this offering are approximately $7,000,000, before deducting underwriting discounts, commissions and other offering expenses. The Warrants have an exercise price of $0.385, are exercisable upon issuance and expire 14 months from the date of issuance. Heat Biologics, Inc. has granted the underwriters a 45-day option to purchase up to 3,000,000 additional shares of Common Stock and/or additional Warrants to purchase up to 1,500,000 shares of Common Stock to cover over-allotments, if any.

A.G.P./Alliance Global Partners is acting as the sole book-running manager for the offering.

Brookline Capital Markets, a division of Arcadia Securities, LLC and Maxim Group LLC are acting as co-managers for the offering.

A registration statement on Form S-1 (File No. 333-234105) relating to these securities has been filed with the U.S. Securities and Exchange Commission ("SEC") and became effective on January 16, 2020 and is available on the SEC’s website located at View Source This offering is being made only by means of a prospectus. Electronic copies of the final prospectus may be obtained from A.G.P./Alliance Global Partners, 590 Madison Avenue, 36th Floor, New York, NY 10022 or via telephone at 212-624-2060 or email: [email protected].

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

US Food and Drug Administration (FDA) grants priority review of belantamab mafodotin for patients with relapsed or refractory multiple myeloma

On January 21, 2020 GlaxoSmithKline plc (LSE/NYSE: GSK) reported the US Food and Drug Administration (FDA) granted a priority review for the company’s Biologics License Application (BLA) seeking approval of belantamab mafodotin (GSK2857916) for the treatment of patients with relapsed or refractory multiple myeloma whose prior therapy included an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody (Press release, GlaxoSmithKline, JAN 21, 2020, View Source [SID1234553362]).

The BLA is based on data from the pivotal DREAMM-2 (DRiving Excellence in Approaches to Multiple Myeloma) study, recently published in The Lancet Oncology, which enrolled heavily pre-treated patients who had actively progressing multiple myeloma that had worsened despite current standard of care.[1]

In 2017, belantamab mafodotin was granted Breakthrough Therapy designation by the FDA, which is intended to facilitate the development of investigational medicines that have shown clinical promise for conditions where there is significant unmet need.

About B-cell maturation antigen (BCMA)
The normal function of BCMA is to promote plasma cell survival by transduction of signals from two known ligands, BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand). This pathway has been shown to be important for myeloma cell growth and survival. BCMA expression is limited to B cells at later stages of development. BCMA is expressed at varying levels in myeloma patients and BCMA membrane expression is universally detected in myeloma cell lines.[2]

About multiple myeloma
Multiple myeloma is the second most common blood cancer and is generally considered treatable, but not curable.[3] In the US, more than 32,000 people were diagnosed with multiple myeloma last year and nearly 13,000 people died from the disease.[4] Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.[5]

About the DREAMM clinical trial programme for belantamab mafodotin (GSK2857916)
Belantamab mafodotin is an investigational immunoconjugate comprising a humanised anti-B cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent auristatin F via non-cleavable linker. The drug linker technology is licensed from Seattle Genetics; monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa.

Belantamab mafodotin is not currently approved for use anywhere in the world.

Trial Name

GSK ID/NCT ID

Status

Design

DREAMM-1

117159/ NCT02064387

Completed

A Phase I Open-label Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of Belantamab Mafodotin (GSK2857916) in Subjects with Relapsed/Refractory Multiple Myeloma and Other Advanced Hematologic Malignancies Expressing BCMA

DREAMM-2

205678/ NCT03525678

Active, not recruiting

A Phase II Study to Investigate the Efficacy and Safety of Two Doses of Belantamab Mafodotin (GSK2857916) in Subjects with Relapsed/Refractory Multiple Myeloma Who are Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed Prior Treatment with an Anti-CD38 Antibody

DREAMM-3

207495/ NCT04162210

Planned

A Phase III Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin (GSK2857916) Compared to Pomalidomide plus low-dose Dexamethasone (Pom/Dex) in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-4

205207/ NCT03848845

Recruiting

A Phase I/II Single Arm Open-Label Study to Explore Safety and Clinical Activity of Belantamab Mafodotin (GSK2857916) Administered in Combination with Pembrolizumab in Subjects with Relapsed/Refractory Multiple Myeloma

DREAMM-5

208887/

NCT04126200

Recruiting

A Phase I/II, Randomized, Open-label Platform Study of Belantamab Mafodotin (GSK2857916) with Innovative Combination Anti-Cancer Treatments in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-6

207497/ NCT03544281

Recruiting

A Phase I/II Randomized Study to Evaluate Safety, Tolerability and Clinical Activity of Belantamab Mafodotin (GSK2857916) Administered in Combination with Lenalidomide plus Dexamethasone (Arm A), or in Combination with Bortezomib plus Dexamethasone (Arm B) in Subjects with Relapsed/Refractory Multiple Myeloma

DREAMM-7

207503

Planned

A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Bortezomib plus Dexamethasone versus Daratumumab, Bortezomib, and Dexamethasone in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-8

207499

Planned

A Phase III, Multicentre, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin (GSK2857916) in Combination with Pomalidomide plus Low-Dose Dexamethasone (BPd) versus Pomalidomide plus Bortezomib and Low-Dose Dexamethasone (PVd) in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-9

209664/ NCT04091126

Recruiting

A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Bortezomib plus Lenalidomide and Low-Dose Dexamethasone (VRd) vs. VRd in Participants with Newly Diagnosed Multiple Myeloma who are Ineligible for Transplant

DREAMM-10

207500

Planned

A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with a Novel Agent versus SoC

ISS / GSK Co-Sponsored Study

209418/ NCT03715478

Recruiting

A Phase I/II Dose-escalation and Dose-expansion Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Pomalidomide plus Low-dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma Who Have Received Two or More Prior Lines of Therapy That Must Have Included Lenalidomide and a Proteasome Inhibitor

GSK in Oncology
GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics, and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

Scientists study zebrafish in search of melanoma-fighting drugs

On January 21, 2020 Northern Arizona University reported that melanoma is the most lethal type of skin cancer and unusually common in Arizona, where residents are exposed to higher-than-average amounts of ultraviolet radiation (Press release, Northern Arizona University, JAN 21, 2020, View Source [SID1234553361]). However, Northern Arizona University scientists believe the formula for a combination of melanoma-fighting drugs is within reach.

Matthew Salanga, an assistant professor in NAU’s Department of Biological Sciences, is leading an 18-month project funded through a Flinn Foundation grant of $100,000. His team, which includes experts in experimental biology, computational systems biology and translational medicine, will study melanoma tumors on zebrafish, a small minnow-sized fish that has 70 percent of the same genes that are found in humans. Physiologically, zebrafish also have pigment cells in their skin, called melanocytes, which give them their stripes and their name. In humans, these cells are responsible for creating a tan when exposed to the sun, and if dysregulated can give rise to melanoma.

The majority of melanoma skin cancers are the result of a specific mutation in the BRAF gene (BRAF V600E). BRAF is a type of enzyme known as a protein kinase that adds a phosphate group to other proteins in cell signaling pathways. For this project, zebrafish that express the human form of mutated BRAF are employed to test strategies for treating melanoma.

"Fish don’t often get cancer," said Salanga, an expert in cell and developmental biology, "but in the lab, we can engineer fish to contain human genes that we know are associated with cancer. Essentially, it’s a way to use non-human vertebrates as though they were human. We call this humanization."

Currently there are around 30 zebrafish carrying the BRAF V600E human oncogene in Salanga’s lab that have visible melanoma tumors, and that number will grow as the study progresses. Activated BRAF acts to promote cell growth and proliferation. Salanga explains that the V600E mutation of BRAF leaves it stuck in the "on" position. This can result in unrestricted cell growth and proliferation. Drugs have been developed that specifically target and suppress tumor cells that have aberrant BRAF kinase activity. These drugs are in a class of drug called protein kinase inhibitors (PKIs), and are currently used clinically. However, not all patients respond and many relapse after a few months of therapy.

Researchers try to predict best drug combinations for inhibiting kinase activity

Salanga believes that there is a combination and dosage of PKIs recognizing distinct conformations of the BRAF kinase that can shut down the misfiring proteins and kill tumor cells dependent on oncogenic BRAF activity.

"The crux of the project is trying to predict which set of currently available drugs will work the best at inhibiting BRAF’s ability to turn things on inappropriately," he said. "Molecular profiling of tumor cells might be used to guide the drug selection for individual patients."

Critical to the NAU-based pilot project team is Richard Posner, a professor in NAU’s Department of Biological Sciences and William Hlavacek, a scientist at Los Alamos National Laboratory. Posner and Hlavacek are computational systems biologists who have developed mathematical models for predicting optimal strategies to target mutations in BRAF. In recent work, they and their collaborators predicted that two-drug combinations will be able to effectively suppress mutant BRAF (V600E) signaling. These predictions were validated in melanoma cell lines. The researchers are leveraging this computation pipeline to predict therapeutic responses to novel combinations of U.S. Food and Drug Administration-approved drugs in humanized zebrafish harboring melanoma skin cancer.

Also involved in the project is Haiyong Han, a scientist in the Molecular Medicine Division at the Translational Genomics Research Institute (TGen). His specialty is pancreatic cancer, which could potentially be treated using similar therapeutic strategies that are being proposed for melanoma.

The researchers, including undergraduate and graduate students, will be adding various combinations of inhibitors to see if they can find combinations that are most effective in targeting mutated RAF proteins.

Salanga says taking the melanoma-fighting research from the lab to medical facilities could happen quickly, as 150 PKIs are already in various stages of safety testing, and many are approved by the FDA.

"TGen and its partners can carry out these PKI clinical trials fairly routinely through its patient network and its scientists, who assist in these human studies. We could see humans receiving treatments like this within the next year or two," he said.

Although early detection of melanoma contributes to an 89 percent, five-year survival rate, metastatic melanoma is often lethal, with less than a 20 percent survival rate.

NAU’s grant for the project was awarded by the Flinn Foundation under its Seed Grants to Promote Translational Research initiative.

Blueprint Medicines Announces Proposed Public Offering of Shares of Common Stock

On January 21, 2020 Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported that it has commenced an underwritten public offering of $325,000,000 in shares of its common stock (Press release, Blueprint Medicines, JAN 21, 2020, View Source [SID1234553360]). In addition, Blueprint Medicines expects to grant the underwriters a 30-day option to purchase up to an additional $48,750,000 in shares of its common stock in connection with the public offering. All shares of common stock will be offered by Blueprint Medicines.

Blueprint Medicines expects to use the net proceeds of the offering to further build its global commercial infrastructure to support additional planned regulatory filings and commercial launches for AYVAKIT and pralsetinib, if approved, in the U.S. and Europe; to fund clinical trials for avapritinib in systemic mastocytosis (SM), including its ongoing registration-enabling Phase 2 PIONEER clinical trial for indolent and smoldering SM, as well as future indication expansion clinical trials; to fund clinical trials for pralsetinib in RET-driven cancers, including its Phase 3 AcceleRET Lung clinical trial for pralsetinib in first-line RET-altered NSCLC and its planned Phase 3 clinical trial for pralsetinib in first-line RET-mutant MTC, as well as future indication expansion clinical trials; to fund its planned Phase 1 trial for BLU-263 in healthy volunteers and future clinical trials for BLU-263 and other future drug candidates; to fund manufacturing costs for AYVAKIT and for ongoing and anticipated drug development efforts for its most advanced drug candidates; and the balance, if any, to fund additional discovery research efforts, its other ongoing and planned clinical trials, working capital requirements and other general corporate purposes.

Goldman Sachs & Co. LLC and Cowen and Company, LLC are acting as joint book-running managers for the offering. Canaccord Genuity LLC, JMP Securities LLC, and Raymond James & Associates, Inc. are acting as co-lead managers for the offering. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed or as to the actual size or terms of the offering.

A registration statement on Form S-3 (File No. 333-216573) relating to these securities has been previously filed with the Securities and Exchange Commission (SEC) and has become effective. This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

The offering will be made only by means of a prospectus. A copy of the prospectus supplement relating to the offering will be filed with the SEC and may be obtained, when available, from Goldman Sachs & Co. LLC by mail at Prospectus Department, 200 West Street, New York, NY 10282, by telephone at (866) 471-2526, by fax at (212) 902-9316, or by email at [email protected], or from Cowen and Company, LLC, c/o Broadridge Financial Services, 1155 Long Island Avenue, Edgewood, NY 11717, Attention: Prospectus Department, or by telephone at (833) 297-2926.

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Month: January 2020

Chi-Med Announces Proposed Public Offering of ADSs

Heat Biologics, Inc. Announces Closing of $7,000,000 Public Offering

US Food and Drug Administration (FDA) grants priority review of belantamab mafodotin for patients with relapsed or refractory multiple myeloma

Scientists study zebrafish in search of melanoma-fighting drugs

Blueprint Medicines Announces Proposed Public Offering of Shares of Common Stock