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Aptose Prioritizes Development of CG’806 First-in Class FLT3/BTK Inhi

On January 23, 2017 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS), a clinical-stage company developing new therapeutics and molecular diagnostics that target the underlying mechanisms of cancer, reported it will prioritize its resources toward the development of CG’806, an oral preclinical compound being developed for patients with FLT3-driven acute myeloid leukemia (AML) and certain BTK-driven B-cell malignancies (Press release, Aptose Biosciences, JAN 23, 2017, View Source [SID1234539165]). Aptose will temporarily delay clinical activities with APTO-253, a phase 1 stage compound for AML, in order to elucidate the cause of recent manufacturing setbacks related to the intravenous formulation of APTO-253, with the intention of restoring the molecule to a state supporting clinical development and partnering.

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Although Aptose has two compelling cancer drugs, current resources can support the full development activities of only one at this time. Recent advances with CG’806 have elevated this agent as having the best risk-reward profile to pursue with those resources. Such data established CG’806 as a well-differentiated pan-FLT3 inhibitor that demonstrates tumor eradication in the absence of toxicity in AML xenograft models, and it is on track for development as a therapy for certain AML patients. In addition, CG’806 is a potent non-covalent inhibitor of proliferation among certain BTK-driven B-cell derived cancer cells. The encouraging properties of CG’806, including its potency against well-established targets in diseases of severe medical need, warrant expeditious advancement and prioritization of resources toward this molecule.

"Concurrent evidence of a unique activity profile with CG’806 along with manufacturing delays for APTO-253 have led us to reprioritize our corporate strategy," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "While we remain confident in the viability of APTO-253 as a potential treatment for AML, we believe the greater value proposition to shareholders and patients is to focus our available resources on CG’806."

In November 2015, Aptose’s phase 1b trial of APTO-253 in patients with AML was placed on clinical hold. Since that time, the company has actively evaluated multiple formulation and production methodologies with the goal of developing a superior IV formulation. After successfully manufacturing multiple non-cGMP batches of a new drug product formulation for APTO-253, including a batch that has been stable and soluble for over six months, the company recently encountered an additional manufacturing setback which further delayed the return of APTO-253 to the clinic. While Aptose has made significant advances in understanding the novel c-Myc inhibitory mechanism of APTO-253, additional time will be required to define the cause of the cGMP manufacturing delay and to potentially restore APTO-253 to a state it can be developed clinically and partnered.

Based on information currently available, Aptose expects to report total cash and cash equivalents to be at a similar level as at September 30, 2016. As a result of activities to reprioritize its resources towards the development of CG’806, the cash on hand, which includes additional cash raised through its At-The-Market facility, is expected to provide sufficient resources to fund research and development and operations into Q4, 2017. Information reported above with respect to the financial year ended December 31, 2016 are preliminary and are subject to change and adjustment as the company’s 2016 financial results are finalized. Accordingly, investors are cautioned not to place undue reliance on the foregoing guidance. The company does not intend to continue to provide preliminary results in the future. Aptose expects to report its financial results for the financial year ended December 31, 2016 on or around March 14, 2016.

About CG’806

CG ‘806 is a once daily, oral, first-in-class FLT3/BTK inhibitor. This small molecule demonstrates potent inhibition of mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain), eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the Cys481Ser mutant of the BTK enzyme, suggesting the agent may be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.

Conference Call and Webcast

Aptose will host a conference call this morning, Monday, January 23, 2017 at 8:30 AM ET. Participants can access the conference call by dialing toll-free (844) 882-7834 (North America toll-free number) or (574) 990-9707 (international dial-in number), using the conference call passcode 58646784. The conference call can also be accessed here and will be available through a link on the Investor Relations section of Aptose’s website at ir.aptose.com. An archived version of the webcast will be available on the company’s website for 30 days.

PRIMA BIOMED TO PRESENT AT 2ND ANNUAL CANCER IMMUNOTHERAPY CONFERENC

On January 23, 2017 Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD) ("Prima" or the "Company") reported that the submission titled "TACTI-mel, Two ACTive Immunotherapies in Melanoma: Combination of IMP321 (LAG-3Ig) with an Anti-PD-1 Antagonist in a Phase I Trial" has been accepted for a presentation at the 2nd Annual Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper), part of 24th International Molecular Medicine Tri-Conference, in San Francisco, California, between February 20 – 22, 2017 (Press release, Prima Biomed, JAN 23, 2017, View Source [SID1234517536]).

Prima’s Chief Medical & Scientific Officer, Dr Frédéric Triebel, will deliver the presentation between 12:00pm – 12:30pm on Monday, February 20, which will be based on the pre-clinical results for the anti-PD-1/IMP321 combination and TACTI-mel trial design. A copy of these presentation slides will be made available on the Prima BioMed website at this time.

Further information on the conference can be found at View Source

About IMP321
IMP321, a first-in-class Antigen Presenting Cell (APC) activator based on the immune checkpoint LAG-3, represents one of the first proposed active immunotherapy drugs in which the patient’s own immune system is harnessed to respond to tumour antigenic debris created by chemotherapy. As an APC activator IMP321 boosts the network of dendritic cells in the body that can respond to tumour antigens for a better anti-tumour CD8 T cell response.

Combination data of TLR9 agonist lefitolimod with checkpoint inhibitors in preclinical tumor models

On January 23, 2017 MOLOGEN AG (ISIN DE0006637200; Frankfurt Stock Exchange Prime Standard: MGN) reported first combination data of its TLR9 agonist lefitolimod with checkpoint inhibitors (Press release, Mologen, JAN 23, 2017, View Source [SID1234517532]).
The data show that lefitolimod, a so-called Immune Surveillance Reactivator (ISR), can significantly improve the anti-tumor effect of checkpoint inhibitors, particularly anti-PD-1 and anti-PD-L1 antibodies, and thus prolong survival in murine tumor models. The beneficial effect of the combination of lefitolimod with anti-PD-1 compared to each monotherapeutic approach was confirmed in in-vitro experiments. All these results constitute a first preclinical confirmation of the combination approach of lefitolimod with checkpoint inhibitors in the treatment of cancer.

"We believe that patients can benefit from the combination of these immunotherapies due to their modes of action complementing each other. The new results are an important proof-of-concept for the combination approach of lefitolimod with checkpoint inhibitors. Consequently, the data open further application possibilities for our lead product, and support our ongoing phase I combination study of lefitolimod with the checkpoint inhibitor Yervoy ", said Dr. Mariola Söhngen, CEO of MOLOGEN AG.

The clinical combination study titled "A Phase I Trial of Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist) in Patients with Advanced Solid Malignancies" is conducted by MD Anderson Cancer Center (MD Anderson). MOLOGEN provides the Immune Surveillance Reactivator (ISR) lefitolimod and funds the study. Around 50-60 patients will participate in the MD Anderson Cancer Center study in Houston, Texas, U.S.. Patient recruitment began in July 2016 and is expected to be completed at the beginning of 2018.

The primary aim of the study is to determine the best tolerable dose for lefitolimod in combination with Yervoy. The safety of this combination therapy will also be investigated and an expansion phase is planned to evaluate the efficacy of this combination therapy.

Results of the combination of lefitolimod with checkpoint inhibitors in preclinical tumor models have been presented at the Annual 2017 Gastrointestinal Cancers Symposium in San Francisco, USA (January 19-21, 2017).

Landmark First-In-Human Clinical Study Launch Using a Genetically Engineered Natural Killer Cell for the Treatment of Cancer

On January 23, 2017 NantKwest Inc. (Nasdaq:NK), a pioneering, next-generation, clinical-stage immunotherapy company focused on harnessing the unique power of the immune system using natural killer (NK) cells to treat cancer, infectious diseases, and inflammatory diseases, reported that the U.S. Food and Drug Administration (FDA) has authorized the company’s Investigational New Drug Application (IND) for its first-in-human, high-affinity natural killer (haNK) cell therapy Phase I clinical study (Press release, NantKwest, JAN 23, 2017, http://ir.nantkwest.com/phoenix.zhtml?c=254059&p=RssLanding&cat=news&id=2239055 [SID1234517523]).

The company plans to promptly initiate this trial, which is believed to be the first ever clinical evaluation of a genetically engineered, allogenic, off-the-shelf, natural killer cell for the treatment of patients with cancer.

"We are thrilled to have received notification from the FDA that our first haNK cell therapy program has been authorized to proceed into Phase I clinical trials and are focused on moving swiftly to begin this study," said Patrick Soon-Shiong, MD, Chairman and CEO of NantKwest. "The FDA’s authorization to initiate this clinical trial achieves a significant milestone for NantKwest as we begin clinical investigation of the use of haNK cell therapy for the treatment of cancer in a wide range of cancer types."

haNK Cell Therapy Platform

NantKwest’s haNK cell therapy platform, developed to be an allogeneic, off-the-shelf therapy, is focused on optimizing the key role that natural killer cells play in mediating innate immunity, enhancing adaptive immune responses, and, specifically in the case of haNK, improving anti-tumor responses via antibody-dependent cell-mediated cytotoxicity (ADCC).

To achieve this objective, haNK cells have been engineered to express IL-2 and the high-affinity variant of the CD16 receptor (V158 FcγRIIIa). In preclinical studies, the addition of haNK to a variety of therapeutic antibodies has led to increased tumor cell killing when compared to the antibody alone. Thus, this first-in-human clinical study is designed to provide the necessary safety data to rapidly transition to haNK-antibody combination trials.

Dr. Soon-Shiong added, "As only about 10% of patients are born with the high affinity CD16 receptor, we believe the potential for haNK cell therapy to improve patient outcomes for the other 90% of the patient population and become part of the standard-of-care for cancer patients is very compelling."

Study Background

The primary objective of the study is to determine the safety of haNK cell monotherapy administered intravenously once per week in up to 16 patients with metastatic or locally advanced solid tumors. Other objectives include determination of objective response rate, progression-free survival, overall survival, and any correlations between tumor molecular profiles (based on genomics, transcriptomics, and quantitative proteomics) and patient outcomes.

For additional information, including exclusion and inclusion criteria, contact information and other details, please visit www.clinicaltrials,gov, QUILT trial #3.028.

Sunesis Pharmaceuticals Announces Clinical and Regulatory Updates to SNS-062 and Vosaroxin Programs

On January 23, 2017 Sunesis Pharmaceuticals, Inc. (Nasdaq:SNSS) reported clinical and regulatory updates to its two lead programs, SNS-062, a second-generation reversible and non-covalent BTK inhibitor, and vosaroxin, an anti-cancer quinolone derivative currently under review for marketing authorization as a treatment for relapsed/refractory acute myeloid leukemia (AML) in Europe (Press release, Sunesis, JAN 23, 2017, View Source;p=RssLanding&cat=news&id=2238918 [SID1234517515]).

For SNS-062, the company announced that its Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) is now active, supporting the initiation of a Phase 1B/2 study to assess the candidate’s safety and efficacy in patients with advanced B-cell malignancies after prior ibrutinib exposure, including in patients with C481S mutations.

"With a now active IND for SNS-062, another important milestone in the rapid development of this next generation product candidate, we will work toward site activation at our U.S. clinical centers and dosing of the first patients within the first half of 2017," said Daniel Swisher, President and Chief Executive Officer of Sunesis. "The data presented at ASH (Free ASH Whitepaper) from our Phase 1A Healthy Volunteer study were encouraging, and we look forward to understanding the potential for SNS-062 to address the growing unmet needs of patients with B-cell malignancies."

The company also announced today continued progress with its Marketing Authorization Application (MAA) for vosaroxin. Sunesis recently received the Day 180 List of Outstanding Issues, issued by the Committee for Medicinal Products for Human Use (CHMP) as part of the centralized review process.

Mr. Swisher continued, "We are working diligently to complete a comprehensive and detailed response to the Day 180 List of Outstanding Issues, which we expect to submit by the end of the first quarter. As we enter the final phase of the European approval process for vosaroxin, we are preparing to go before the Scientific Advisory Group’s Oncology Division (SAG-O) in April, which will assist the CHMP in its evaluation of our application. We anticipate a decision from the CHMP by mid-year and continue to advance active dialogues with potential pharma collaborators toward the goal of supporting a market launch of vosaroxin in 2017."

About SNS-062

SNS-062 is a novel, second-generation BTK inhibitor, a class of kinase inhibitors that selectively inhibits the enzyme Bruton’s tyrosine kinase (BTK). This target mediates signaling through the B-cell receptor, which is critical for adhesion, migration, proliferation and survival of normal and malignant B-lineage lymphoid cells. Unlike other drugs in its class, SNS-062 binds non-covalently and reversibly to the BTK enzyme. Its binding profile along with improved PK/PD properties potentially provide SNS-062 an opportunity to address the leading acquired resistance to ibrutinib, a mutation in the enzyme’s binding site required for covalent binding. In preclinical studies, SNS-062 demonstrated potent activity against C481S mutated B-cell malignancies, and has been studied in healthy subjects in a completed Phase 1A, randomized, double-blind, placebo-controlled dose-ranging study to investigate the drug’s safety, pharmacokinetics, and pharmacodynamics. With the reported successful study outcome, SNS-062 is proceeding to a Phase 1B/2 study in patients with B-cell malignancies.

About QINPREZO (vosaroxin)

QINPREZO (vosaroxin) is an anti-cancer quinolone derivative (AQD), a class of compounds that has not been used previously for the treatment of cancer. Preclinical data demonstrate that vosaroxin both intercalates DNA and inhibits topoisomerase II, resulting in replication-dependent, site-selective DNA damage, G2 arrest and apoptosis. Both the U.S. Food and Drug Administration (FDA) and European Commission have granted orphan drug designation to vosaroxin for the treatment of AML. Vosaroxin is an investigational drug that has not been approved for use in any jurisdiction.

Vosaroxin’s Marketing Authorization Application for relapsed refractory AML is currently under review by the European Medicines Agency, and a regulatory decision regarding approval is expected in 2017.

The trademark name QINPREZO is conditionally accepted by the FDA and the EMA as the proprietary name for the vosaroxin drug product candidate.