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Astex to Showcase Its Next-Generation Hypomethylating Agents Being Developed for Treatment
of AML/MDS at the 2016 Annual Meeting of the American Society of Hematology

On November 29, 2016 Astex Pharmaceuticals, a member of the Otsuka group, reported that investigators collaborating with Astex will present results from several studies evaluating guadecitabine, its subcutaneous, next-generation hypomethylating agent; and ASTX727, its novel, oral hypomethylating agent at the 2016 Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, California, December 3 to 6 (Press release, Astex Pharmaceuticals, NOV 29, 2016, View Source [SID1234516839]).

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The oral presentations are as follows:

Initial results of a Phase 2 Study of Guadecitabine (SGI-110), A Novel Subcutaneous (sc) Hypomethylating Agent, for Patients with Previously Untreated Intermediate-2 or High Risk Myelodysplastic Syndromes (MDS) or Chronic Myelomonocytic Leukemia (CMML) (Abstract #346). Dr. Guillermo Montalban-Bravo et al. Sunday, December 4, 10:15 am; Manchester Grand Hyatt, Grand Hall C.
Results of a Phase II study of Guadecitabine (SGI-110) in higher risk MDS, CMML or low-blast- count AML patients refractory to or relapsing after Azacitidine (AZA) treatment (Abstract #347). Dr. Marie Sebert et al. Sunday, December 4, 10:30 am; Manchester Grand Hyatt, Grand Hall C.
Long Term Survival and Clinical Complete Responses of Various Prognostic Subgroups in 103 Relapsed/Refractory Acute Myeloid Leukemia (r/r AML) Patients Treated with Guadecitabine (SGI-110) in Phase 2 Studies (Abstract #904). Dr. Naval Daver et al. Monday, December 5, 3:30 pm; Marriott Marquis San Diego Marina, San Diego Ballroom AB.
Successful Emulation of IV Decitabine Pharmacokinetics with an Oral Fixed-Dose Combination of the Oral Cytidine Deaminase Inhibitor (CDAi) E7727 with Oral Decitabine, in Subjects with Myelodysplastic Syndromes (MDS): Final Data of Phase 1 Study (Abstract #114). Dr. Guillermo Garcia-Manero et al. Saturday December 3, 10:45 am; Manchester Grand Hyatt, Grand Hall C.
In addition, a poster presentation entitled: Genetic determinants of response to guadecitabine (SGI-110) in AML (Abstract #1680), Dr. Patricia L. Kropf et al., will be made on Saturday, December 3, 9:30 am to 11 am in the San Diego Convention Center, Hall GH.

Data from the guadecitabine Phase 2 study (www.clinicaltrials.gov, NCT01261312) has helped to inform the design of the 800-patient, global Phase 3 study of guadecitabine in adults with previously untreated AML who are not considered candidates for intensive induction chemotherapy (ASTRAL-1, www.clinicaltrials.gov, NCT02348489), and the newly announced global Phase 3 studies in relapsed / refractory AML (ASTRAL-2, www.clinicaltrials.gov, NCT02920008), and relapsed / refractory MDS or CMML (ASTRAL-3, www.clinicaltrials.gov, NCT02907359). Astex also announced today that enrollment into the ASTRAL-1 study is now complete. The data on ASTX727 being reported at ASH (Free ASH Whitepaper) also informed the design of a Phase 2 randomized, cross-over study comparing ASTX727 to decitabine IV in higher risk MDS, which is ongoing.

"The data from these clinical studies helps to validate the development of these agents for the treatment of AML and MDS, potentially providing new treatment options for patients with these aggressive hematological malignancies," said Mohammad Azab, President and Chief Medical Officer of Astex. "We are delighted to be working with some of the world’s leading experts in the treatment of hematological malignancies in bringing these next-generation therapies to patients."

About Guadecitabine (SGI-110)

Guadecitabine is a novel next-generation, small-molecule DNA hypomethylating agent formulated as a single, small-volume, subcutaneous injection. The product was designed to deliver longer exposure to the active metabolite, decitabine, compared to IV decitabine, and more efficient delivery into key tissues, including the bone marrow. Guadecitabine demonstrated activity in restoring silenced tumor suppressor gene expression in cancer cells by reversal of DNA methylation and inducing responses in previously treated MDS and AML patients. Guadecitabine is currently being investigated in multiple clinical trials, including the ASTRAL series of studies and an extensive program of investigational studies in combination with immunotherapy and other anti-neoplastic agents, for the treatment or a range of hematological malignancies and solid tumors.

About ASTX727

ASTX727 is a unique fixed-dose combination of the hypomethylating agent decitabine, the active ingredient in Dacogen, and the novel cytidine deaminase inhibitor, E7727. ASTX727 was designed to deliver decitabine by oral administration. By inhibiting cytidine deaminase, E7727 inhibits the major mechanism by which decitabine is degraded in the gut, and the combination therefore permits the efficient oral delivery of decitabine at a low dose. Astex is completing a Phase 2 clinical study of ASTX727 in the treatment of intermediate and high risk myelodysplastic syndromes (MDS).

Guadecitabine and ASTX727 are investigational agents, and efficacy and safety have not been established. There is no certainty that these agents will become commercially available.

Celldex Therapeutics Completes Acquisition of Kolltan Pharmaceuticals

On November 29, 2016 Celldex Therapeutics, Inc. (Nasdaq:CLDX) reported it has completed its previously announced acquisition of Kolltan Pharmaceuticals, Inc., a privately held company focused on the discovery and development of novel, antibody-based drugs targeting receptor tyrosine kinases (RTKs) (Press release, Celldex Therapeutics, NOV 29, 2016, View Source [SID1234516835]).

"Celldex has added a unique platform of antibodies targeting receptor tyrosine kinases, which are validated targets in oncology, to our pipeline. Clinical and preclinical data suggest these candidates can help overcome tumor resistance mechanisms associated with current tyrosine kinase inhibitors and seen in patients who have failed other cancer therapies," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex. "We believe these programs are highly compatible with our scientific approach and can be developed independently and in combination with Celldex’s existing product candidates. We are finalizing our integrated clinical development strategy and look forward to outlining these plans in the coming weeks."

The following programs have been added to the Celldex pipeline:

CDX-0158 (formerly KTN0158) — a humanized monoclonal antibody that is a potent inhibitor of KIT activation and receptor dimerization in tumor cells and mast cells, which is currently in a Phase 1 dose escalation study in refractory gastrointestinal stromal tumors (GIST).

CDX-3379 (formerly KTN3379) — a human monoclonal antibody designed to block the activity of ErbB3 (HER3), which recently completed a Phase 1b study with combination cohorts where meaningful responses and stable disease were observed in cetuximab (Erbitux) refractory patients in head and neck squamous cell carcinoma and in BRAF-mutant non-small cell lung cancer (NSCLC).

A multi-faceted TAM program — a broad antibody discovery effort underway to generate antibodies that modulate the TAM family of RTKs, comprised of Tyro3, AXL and MerTK, which are expressed on tumor-infiltrating macrophages, dendritic cells and some tumors. Research supports TAMs having broad application and potential across immuno-oncology and inflammatory diseases.

PharmaCyte Biotech Granted FDA Pre-IND Meeting for Pancreatic Cancer Therapy

On November 29, 2016 PharmaCyte Biotech, Inc. (OTCQB:PMCB), a clinical stage biotechnology company focused on developing targeted treatments for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that a Pre-Investigational New Drug (Pre-IND) meeting with the Center for Biologics Evaluation and Research (CBER) of the U.S. Food and Drug Administration (FDA) has been granted by the FDA (Press release, PharmaCyte Biotech, NOV 29, 2016, View Source [SID1234516834]). During the meeting with representatives from CBER, they will respond to PharmaCyte’s previously submitted questions to the FDA as part of a Pre-IND information package related to PharmaCyte’s clinical trial in locally advanced, inoperable pancreatic cancer (LAPC).

PharmaCyte will be submitting a full Pre-IND package of information to the FDA that describes what PharmaCyte intends on submitting in its Investigational New Drug (IND) application. The FDA will review PharmaCyte’s manufacturing, preclinical pharmacology and toxicology and clinical trial plans for the company’s therapy to treat LAPC. After the FDA has responded to the questions and issued comments, PharmaCyte will undertake steps to address them to the FDA’s satisfaction which will lead directly to the preparation of the IND application itself. Once the IND application is found to be acceptable to the FDA, patients can be enrolled in PharmaCyte’s clinical trial.

PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, commented about the Pre-IND meeting saying, "We are pleased that the FDA has granted us a Pre-IND meeting in connection with our planned clinical trial for LAPC patients whose disease has already received maximum response from the gold standard of care – the combination therapy of Abraxane plus gemcitabine. Our Pre-IND meeting is the next step in getting our pancreatic cancer therapy into a clinical trial and approved by the FDA. We believe PharmaCyte is well on its way to accomplishing this goal."

PharmaCyte’s clinical trial in patients with LAPC is designed to meet a clear unmet medical need for those whose cancer no longer responds after 4-6 months of treatment with the combination of Abraxane plus gemcitabine. The trial will be open-label and multi-site in nature, with sites in the U.S. and Europe. Patients with LAPC will be randomized equally into two groups. One group will receive gemcitabine chemotherapy alone, and the other group will receive PharmaCyte’s pancreatic cancer therapy (encapsulated genetically modified live human cells that can activate the cancer prodrug ifosfamide plus low doses of the prodrug to eliminate side effects from the chemotherapy). In addition to comparing the anticancer activity and safety of the two therapies, a major aspect of the trial will be to determine if, and how well, PharmaCyte’s therapy can shrink inoperable tumors so that they may become operable.

Seattle Genetics to Webcast Investor and Analyst Event at American Society of Hematology Annual Meeting

On November 29, 2016 Seattle Genetics, Inc. (NASDAQ:SGEN) reported that the company will webcast an investor and analyst event on Monday, December 5, 2016 during the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, CA (Press release, Seattle Genetics, NOV 29, 2016, View Source;p=RssLanding&cat=news&id=2226084 [SID1234516833]). Members of the Seattle Genetics management team and industry experts will discuss data being presented at the conference, including from the ADCETRIS (brentuximab vedotin) and vadastuximab talirine (SGN-CD33A) programs.

The event will take place from approximately 8:15 p.m. to 9:15 p.m. Pacific Time. The webcast will be available live and for replay from Seattle Genetics’ website at www.seattlegenetics.com in the Investors and News section.

Ignyta to Debut Preclinical Data on RXDX-106 at the 2016 EORTC-NCI-AACR Annual Meeting

On November 29, 2016 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported its first disclosed preclinical data on RXDX-106—its potent, selective, type II pseudo-irreversible inhibitor of TYRO3, AXL and MER (or TAM) and c-MET—will be presented at the 2016 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Molecular Targets and Cancer Therapeutics Symposium in Munich, Germany, highlighting both the immuno-oncology and targeted therapeutic activity of this novel agent (Press release, Ignyta, NOV 29, 2016, View Source [SID1234516832]). Additionally, the company will present data on multiple compounds in clinical development from its robust pipeline of molecularly targeted oncology therapies, including entrectinib—an orally available, CNS-penetrant tyrosine kinase inhibitor targeting tumors that harbor TRK, ROS1 or ALK fusions—and RXDX-105—a VEGFR-sparing, potent RET inhibitor.

"We are pleased to introduce preclinical data on RXDX-106 at ENA alongside our promising clinical data for entrectinib and RXDX-105," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "RXDX-106 is an intriguing, novel agent that may offer a dual mechanism by potentiating the immune system, while also providing selective activity against key molecular targets involved in both primary oncogenesis and resistance."

In the presented preclinical data on RXDX-106, researchers demonstrated that the agent is a potent and selective inhibitor of TAM and c-MET, and inhibited TAM-mediated and c-MET-mediated tumor growth in vivo. Additionally, researchers demonstrated, via in vitro and in vivo studies, that RXDX-106, as a single agent, appears to release the molecular brakes on immune activation in macrophages, NK cells, and T cells, resulting in the repolarization of the immune response to elicit an anti-tumor effect. Furthermore, emerging in vivo combination data suggest that RXDX-106 potentiates the activity of anti-PD-1 and anti-CTLA-4 agents. These data further support the continued evaluation of RXDX-106 in both a preclinical and clinical setting (Abstract number 73, Poster number P044; Abstract number 65, Poster number P036).

Also presented as part of this poster session were preclinical data on RXDX-105 demonstrating significant anti-tumor activity in models harboring RET fusions (Abstract number 85, Poster number P056), as well as preclinical data on entrectinib showing potent anti-tumor activity in multiple different tumor model systems driven by NTRK1/2/3, ROS1 and ALK fusions, regardless of the fusion partners or the tumor tissue of origin (Abstract number 78, Poster number P049). Additional clinical data on RXDX-105 and entrectinib will be presented later in the week at ENA.