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Moffitt Cancer Center and Aptose Biosciences to Present Data on a Novel Class of Dual-Targeting Bromodomain / Kinase Inhibitors at 57th Annual American Society of Hematology (ASH) Meeting

On December 3, 2015 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported that its collaborator, Moffitt Cancer Center, will present preclinical data for its dual-targeting bromodomain (BRD) / kinase inhibitor, MA2-014, at the 57th Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting and Exposition being held December 5-8, 2015, in Orlando, FL (Press release, Aptose Biosciences, DEC 3, 2015, View Source;p=RssLanding&cat=news&id=2119892 [SID:1234508437]).

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The dual-targeting inhibitor MA2-014 is a representative candidate from a new family of small molecule, dual-targeting BRD / kinase inhibitors licensed to Aptose from Moffitt Cancer Center. The MA2-014 program was developed to inhibit both the bromodomain 4 (BRD4) protein and the Janus kinase 2 (JAK2) for the potential treatment of various hematologic and solid tumor cancers. The data being presented by Moffitt researchers reflect in vitro activity of MA2-014 in myeloproliferative neoplasm (MPN) cell lines. MPNs are rare blood cancers including polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF).

Clinically, JAK2 inhibitors alone have demonstrated the ability to improve symptoms of MPNs, but have not been shown to induce remission. Further, combining a bromodomain inhibitor and a JAK2 inhibitor has been shown to be more effective against MPN cells than JAK2 inhibition alone. This provided rationale to develop a single molecule with potent activity against both the bromodomain family proteins and JAK2. Moffitt researchers will present data for MA2-014, a single molecule that exhibits similar anti-JAK2 activity as a known JAK2 inhibitor, TG101209, with an approximate ten-fold improvement in anti-BRD activity. Moffitt researchers also demonstrated a ten-fold improvement in the ability of MA2-014 to inhibit JAK2-V617F signaling over TG101209, and comparable to ruxolitinib. Ruxolitinib is the only FDA approved JAK inhibitor for MPNs. However, MA2-014 retained its potency against ruxolitinib-resistant cells. Moffitt researchers also determined in long-term culture assays that JAK2-V617F driven MPN Uke1 cells do not experience resistance to MA2-014 as readily as they do to TG101209 or ruxolitinib.

"We are excited to continue development of MA2-014 and other candidates in our collaboration with Moffitt and to advance highly differentiated dual-targeting BRD / kinase inhibitors for the treatment of rare blood cancers into the clinic," said William G. Rice, Ph.D., Chairman, President and CEO. "We share Moffitt’s optimism about the potential for dual-targeting BRD / kinase inhibitors as high-value epigenetic drug candidates to provide the benefits of combination therapy for hematologic cancers."

"The development and optimization of a single drug designed to simultaneously inhibit JAK2 kinase and bromodomains of the bromodomain and extraterminal proteins may improve therapy for myeloproliferative neoplasms (MPN), by delivering a potentially effective combination therapy with a single agent," said Gary Reuther, Associate Member of the Cancer Biology and Evolution Program at Moffitt. "Such dual inhibition of these targets and their respective pathways may provide a new effective MPN therapy and reduce the development of drug resistance seen with JAK2 inhibitors."

Abstract Details

Title: "Single Molecule Dual JAK2-BET Inhibition as an MPN Therapeutic"
* Date/Time: Sunday, December 6, 2015, 6:00 – 8:00 p.m.
* Location: Orange County Convention Center, Hall A, Level 2
* Abstract #: 2826
* Session: 635. Myeloproliferative Syndromes: Basic Science: Poster II

The abstract is available in the online edition of Blood, the official Journal of the American Society of Hematology (ASH) (Free ASH Whitepaper) and on the ASH (Free ASH Whitepaper) conference website.

Aptose previously announced additional ASH (Free ASH Whitepaper) abstracts on its lead clinical candidate APTO-253:

Title: "Broad Activity of APTO-253 in AML and Other Hematologic Malignancies Correlates with KLF4 Expression Level"
* Date/Time: Saturday, December 5, 2015, 5:30-7:30 p.m.
* Location: Orange County Convention Center, Hall A
* Abstract #: 83676
* Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster I

Title: "Clinical Pharmacokinetics of APTO-253 Support its Use as a Novel Agent for the Treatment of Relapsed or Refractory Hematologic Malignancies"
* Abstract #: 4934
* Location: Publication

Strategic Collaboration with Moffitt Cancer Center

Aptose recently entered into a definitive agreement with Moffitt Cancer Center for exclusive global rights to potent, multi-targeting, single-agent inhibitors for the treatment of hematologic and solid tumor cancers. These small molecule agents are highly differentiated inhibitors of the Bromodomain and Extra-Terminal motif (BET) protein family members, which simultaneously target specific kinase enzymes. The molecules developed by Moffitt exhibit single-digit nanomolar potency against the BET family members and specific oncogenic kinases which, when inhibited, are synergistic with BET inhibition. Under the agreement, Aptose gains access to the drug candidates developed by Moffitt and the underlying intellectual property covering the chemical modifications enabling potent bromodomain (BRD) inhibition on the chemical backbone of a kinase inhibitor. Aptose expects lead clinical candidates to emerge from the collaboration by late 2016.

Trillium to Provide Update on Cd47 Immune Checkpoint Inhibitor Program at the 2015 American Society of Hematology Annual Meeting

On December 3, 2015 Trillium Therapeutics Inc. (Nasdaq:TRIL; TSX: TR) an immuno-oncology company developing innovative therapies for the treatment of cancer, reported it will be providing an update on its SIRPaFc immune checkpoint inhibitor program targeting CD47 at the 57th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, Trillium Therapeutics, DEC 3, 2015, View Source [SID:1234508404]). Details of the poster presentation, entitled "SIRPaFc, a CD47- Blocking Cancer Immunotherapeutic, Sensitizes Malignant B cells to MacrophageMediated Destruction," are listed below:

Date: Sunday December 6, 2015
Time: 6:00 pm – 8:00 pm (EST)
Session: 201. Granulocytes, Monocytes and Macrophages: Poster II
Abstract #: 2191
Presenter: Dr. Natasja Nielsen Viller, Research Scientist
Location: Hall A, Orange County Convention Center

The company will present data demonstrating that its SIRPaFc fusion protein, which targets the CD47 "do not eat" signal, triggers macrophage-mediated phagocytosis of a broad range of human B cell tumors and was effective at controlling the growth of aggressive B lymphoma xenografts in mice. Based on the supportive findings of these and other preclinical studies, Trillium is initiating a phase I dose-escalation study of SIRPaFc in patients with advanced lymphoma and other hematological cancers.

"Patients with cancer clearly benefit from immune checkpoint inhibitors," commented Trillium’s Chief Medical Officer, Dr. Eric Sievers. "We hope to show that interrupting the CD47-SIRPa inhibitory synapse with our decoy receptor will have similarly transformative potential."

Lymphoseek® Reduces Sentinel Lymph Node Biopsy Imaging Time, Facilitating Patient Throughput and Workflow Efficiencies

On December 3, 2015 Navidea Biopharmaceuticals, Inc. (NYSE MKT:NAVB) reported that results from an investigator-initiated imaging study demonstrated Lymphoseek (technetium Tc 99m tilmanocept) injection reduced imaging time by more than 50% in sentinel lymph node biopsy procedures in malignant melanoma compared to Tc99m sulfur colloid (SC) (Press release, Navidea Biopharmaceuticals, DEC 3, 2015, View Source;p=RssLanding&cat=news&id=2120146 [SID:1234508398]). This finding suggests hospitals and oncology treatment teams can achieve greater patient throughput and workflow efficiencies utilizing Lymphoseek. Results of the study, conducted at the Thomas Jefferson University Hospitals and led by Charles M. Intenzo, M.D., Professor of Radiology, Director, Nuclear Medicine and Molecular Imaging in the Department of Radiology were presented today at the Radiological Society of North America Annual Meeting (RSNA 2015) in Chicago, Illinois.

"This study continues to support our belief in the clinical value of Lymphoseek for physicians and patients and also introduces an operational efficiency that strengthens the value to the hospital and the overall patient experience," commented Michael Tomblyn, M.D., Navidea’s Chief Medical Officer. "Based on the ability to rapidly clear from the injection site and transit to tumor-draining lymph nodes, we believe that Lymphoseek may facilitate more efficient resource utilization including predictable scheduling of lymphatic mapping procedures, associated personnel and resources."

A total of 34 consecutive patients with malignant melanoma underwent Sentinel Lymph Node (SLN) mapping with Lymphoseek. Patients received the Lymphoseek dose in 4 intradermal administrations around the tumor site. Images were acquired at intervals up to 40 minutes after injection, which is the department’s standard-of-care protocol used for Tc99m Sulfur Colloid (SC) procedures. This site’s previous experience showed that SC injections required 40 to 45 minutes after injection for visualization of all lymph nodes in patients with malignant melanoma. Using Lymphoseek, the results show that in all 34 patients, all lymph nodes seen in the final 40-minute image were identified in the 20-minute image, providing rapid and stable localization and identification of the sentinel nodes. The study concludes that in malignant melanoma, SLN mapping with Lymphoseek involves a total imaging time of 20 minutes which is one-half of the time required for Tc99m SC. From a clinical perspective, the authors conclude that utilizing Lymphoseek is more time-efficient than SC by facilitating patient throughput and expediting subsequent transport to the operating room.

About Lymphoseek

Lymphoseek (technetium Tc 99m tilmanocept) injection is the first and only FDA-approved receptor-targeted lymphatic mapping agent. It is a novel, receptor-targeted, small-molecule radiopharmaceutical used in the evaluation of lymphatic basins that may have cancer involvement in patients. Lymphoseek is designed for the precise identification of lymph nodes that drain from a primary tumor, which have the highest probability of harboring cancer. Lymphoseek is approved by the U.S. Food and Drug Administration (FDA), with or without scintigraphic imaging, for use in solid tumor cancers where lymphatic mapping is a component of surgical management and for guiding sentinel lymph node biopsy in patients with clinically node negative breast cancer, melanoma or squamous cell carcinoma of the oral cavity. Lymphoseek has also received European approval in imaging and intraoperative detection of sentinel lymph nodes in patients with melanoma, breast cancer or localized squamous cell carcinoma of the oral cavity.

Accurate diagnostic evaluation of cancer is critical, as it guides therapy decisions and determines patient prognosis and risk of recurrence. Overall in the U.S., solid tumor cancers may represent up to 1.2 million cases per year. The sentinel node label in the U.S. and Europe may address approximately 235,000 new cases of breast cancer, 76,000 new cases of melanoma and 45,000 new cases of head and neck/oral cancer in the U.S., and approximately 367,000 new cases of breast cancer, 83,000 new cases of melanoma and 55,000 new cases of head and neck/oral cancer diagnosed in Europe annually.

Lymphoseek Indication and Important Safety Information

Lymphoseek is a radioactive diagnostic agent indicated with or without scintigraphic imaging for:

Lymphatic mapping using a handheld gamma counter to locate lymph nodes draining a primary tumor site in patients with solid tumors for which this procedure is a component of intraoperative management.
Guiding sentinel lymph node biopsy using a handheld gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity, breast cancer or melanoma.
Important Safety Information

In clinical trials with Lymphoseek, no serious hypersensitivity reactions were reported, however Lymphoseek may pose a risk of such reactions due to its chemical similarity to dextran. Serious hypersensitivity reactions have been associated with dextran and modified forms of dextran (such as iron dextran drugs).

Prior to the administration of Lymphoseek, patients should be asked about previous hypersensitivity reactions to drugs, in particular dextran and modified forms of dextran. Resuscitation equipment and trained personnel should be available at the time of Lymphoseek administration, and patients observed for signs or symptoms of hypersensitivity following injection.

Any radiation-emitting product may increase the risk for cancer. Adhere to dose recommendations and ensure safe handling to minimize the risk for excessive radiation exposure to patients or health care workers. In clinical trials, no patients experienced serious adverse reactions and the most common adverse reactions were injection site irritation and/or pain (<1%).

CTI BioPharma Announces Proposed Public Offering of Convertible Preferred Stock

On December 3, 2015 CTI BioPharma Corp. ("CTI") (NASDAQ and MTA: CTIC) reported that it intends to offer and sell, subject to market and other conditions, shares of its Series N-2 Preferred Stock in an underwritten public offering (the "Offering") (Press release, CTI BioPharma, DEC 3, 2015, View Source;p=RssLanding&cat=news&id=2120113 [SID:1234508395]). Each share of Series N-2 Preferred Stock will have a stated value of $1,000 per share and will be convertible at the option of the holder, at any time after issuance and subject to certain limitations, into shares of common stock.

Subject to the consummation of the Offering, we have agreed to grant to BVF Partners L.P. the right to nominate two members of our board of directors, one of whom must both qualify as an "independent" director, as defined under the applicable rules and regulations of the U.S. Securities and Exchange Commission and The NASDAQ Stock Market LLC, and must not be considered an "affiliate" of BVF Partners.

CTI plans to use the net proceeds from this Offering to support the commercial launch of pacritinib in the U.S. for patients with myelofibrosis, to conduct additional research concerning the possible application of pacritinib in indications outside of myelofibrosis, to advance the commercialization of PIXUVRI and to support the development of tosedostat in registration-directed trials, as well as for general corporate purposes, which may include funding research and development, conducting preclinical and clinical trials, acquiring or in-licensing potential new pipeline candidates, preparing and filing possible new drug applications and general working capital.

Piper Jaffray & Co. is acting as sole book-running manager for the Offering. The securities described above are being offered by CTI pursuant to a shelf registration statement previously filed with the Securities and Exchange Commission (the "SEC"), which the SEC declared effective on December 8, 2014. A preliminary prospectus supplement related 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 relating to the Offering, when available, may be obtained from Piper Jaffray & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, by email to [email protected] or by telephone at (800) 747-3924.

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 other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction. The shares of Series N-2 Preferred Stock (and the shares of common stock into which each share of Series N-2 Preferred Stock will be convertible) will not be offered, sold or distributed, directly or indirectly, in Italy in an offer to the public of financial products under the meaning of Article 1, paragraph 1, letter t) of Legislative Decree No. 58 of February 24, 1998, as amended (the "Financial Services Act"), unless an express exemption from compliance with the restrictions on offers to the public, including, without limitation, as provided under Article 100 of the Financial Services Act and Article 34-ter of CONSOB Regulation No. 11971 of May 14, 1999, as amended, applies.

Cellectis Announces Conference Call to Discuss UCART19 Development Collaboration with Pfizer and Servier

On December 3, 2015 Cellectis (Alternext: ALCLS – Nasdaq: CLLS) reported that it will host a conference call with Pfizer Inc. (PFE) and Servier on Monday, December 7, 2015 at 8:00 a.m. Eastern Time to discuss their previously announced UCART19 development collaboration (Press release, Cellectis, DEC 3, 2015, View Source [SID:1234508394]).

UCART19 is a TALEN gene-edited allogeneic Chimeric Antigen Receptor T-Cell (CAR-T) immunotherapy developed by Cellectis. On November 19, 2015, Servier exercised its worldwide licensing option with Cellectis to UCART19 and entered into a global UCART19 license and collaboration agreement with Pfizer.

Conference Call Information
Cellectis, Pfizer and Servier management will host a conference call on Monday, December 7, 2015 at 8:00 a.m. ET to discuss UCART19 three-party collaboration.

Dial-In Numbers:
Live Participant Dial-In (Toll-Free US & Canada): 877-407-3104
Live Participant Dial-In (International): +1 201-493-6792
Replay Information:
Conference ID #: 13625168
Replay Dial-In (Toll Free US & Canada): 877-660-6853
Replay Dial-In (International): +1 201-612-7415
Expiration Date: 12/21/15
Webcast URL (Archived for 12 months):
http://cellectis.equisolvewebcast.com/12-7-UCART19