On January 5, 2017 Trethera Corporation and Nanotherapeutics, Inc. reported the signing of an exclusive worldwide agreement whereby Nanotherapeutics has granted Trethera an exclusive license for the global development, manufacturing and marketing of Triapine (3-AP) and all formulations, for the treatment of hematological malignancies (Press release, Nanotherapeutics, JAN 5, 2017, View Source [SID1234517286]). Triapine is a clinical-stage, small molecule inhibitor of ribonucleotide reductase (RNR), a key enzyme in the de novo pathway of nucleotide biosynthesis.

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Trethera has advanced preclinical development of proprietary, small molecule inhibitors of deoxycytidine kinase (dCK), the rate-limiting enzyme in the salvage pathway of nucleotide biosynthesis. Results of its preclinical studies indicate robust and durable anti-leukemic activity of its dCK inhibitors when combined with inhibitors of RNR, and these combinations have demonstrated superior activity over single agent treatments. Trethera aims to commence a Phase I clinical trial for its orally administered, lead dCK inhibitor, TRE-515, in H2 2017.

"This license agreement marks an important step in addressing the needs of patients and physicians combating acute leukemia as well as other blood cancers," said Johanna Holldack, MD, Chief Executive Officer and President of Trethera Corporation. "Our recent non-clinical studies indicate how powerful the combination of Triapine and TRE-515 could be. Securing this partnership accelerates our development pathway and ensures that the potential of this pioneering combination therapy will be fully realized."

Prasad Raje, Ph.D., President and Chief Executive Officer of Nanotherapeutics, commented, "We are delighted to be able to license Triapine to Trethera for the treatment of hematological malignancies. Trethera’s scientific team is pursuing critically important research which may unlock this compound’s ability to yield new blood cancer therapies in the future and we look forward to watching their progress."

On January 5, 2017 Stemline Therapeutics, Inc. (Nasdaq:STML) reported an agreement with the U.S. Food and Drug Administration (FDA) on the registration pathway for SL-401 in blastic plasmacytoid dendritic cell neoplasm (BPDCN) (Press release, Stemline Therapeutics, JAN 5, 2017, View Source [SID1234517283]). To support the filing of a Biologics License Application (BLA) for full approval in first-line BPDCN, Stemline is currently enrolling an additional small cohort, planned for 8-12 first-line BPDCN patients, into its ongoing Phase 2 trial. To date, approximately half of these new patients are enrolled into the study, with full enrollment expected this quarter. Stemline intends to file a BLA in 2H17, which is anticipated to undergo an expedited review given SL-401’s Breakthrough Therapy Designation. If successful, Stemline projects a commercial launch of SL-401 in 2018.

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Ivan Bergstein, M.D., Stemline’s Chief Executive Officer, commented, "We are extremely pleased with the outcome of our meeting with the FDA and the Agency’s continued guidance regarding SL-401, which was granted Breakthrough Therapy Designation this past August. The Agency has now provided us with a clear and potentially rapid pathway to obtain full approval of SL-401 in first-line BPDCN, as well as the possibility for review in the relapsed/refractory setting. We are actively enrolling patients who are to be included in the final cohort of the trial and are targeting completion of enrollment this quarter." Dr. Bergstein continued, "In parallel, our operations and regulatory teams are working hard to ensure a timely and comprehensive BLA filing, including addressing additional data requests from the Agency, while our commercial team is setting the stage, if approved, for a successful launch of SL-401. Additionally, we continue to advance SL-401 into other indications in an effort to provide benefit to patients who are battling aggressive cancers."

Conference Call and Webcast
Stemline Therapeutics will host a conference call and audio webcast Friday, January 6, 2017 at 8:00 AM ET. Interested participants and investors may access the conference call by dialing 888-778-9052 (U.S./Canada) or 913-312-0850 (International) and referencing conference ID: 9093286. An audio webcast can also be accessed via the Investor Relations tab of the Stemline Therapeutics website at View Source

About Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
For more information on BPDCN, please visit Stemline’s patient and physician resource site: www.bpdcninfo.com.

On January 5, 2017 Mirati Therapeutics, Inc. (Mirati or the Company) (NASDAQ: MRTX) reported data from two ongoing clinical programs, including the Phase 1b and Phase 2 trials of glesatinib, a spectrum selective kinase inhibitor for the treatment of non-small cell lung cancer (NSCLC) patients with genetic alterations of MET, and the Phase 1b trial of sitravatinib, a receptor tyrosine kinase inhibitor for the treatment of genetically-selected NSCLC and other solid tumors (Press release, Mirati, JAN 5, 2017, View Source [SID1234517282]).

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"The transition to the new spray dried dispersion (SDD) formulation of glesatinib has succeeded in improving tolerability, resulting in significantly fewer formulation-specific side effects in patients with NSCLC. Early results with the SDD formulation have demonstrated promising activity in NSCLC patients with MET mutations," said Charles M. Baum, M.D., Ph.D., President and CEO of Mirati.

"We are similarly encouraged by data from our Phase 1b trial of sitravatinib, which indicate its potency in RET inhibition. Early results from the trial show clear evidence of tumor responses in NSCLC patients exhibiting RET fusion mutations."

Glesatinib Program Update
The SDD formulation of glesatinib was introduced into the Phase 1b trial and Phase 2 AMETHYST trial in May of 2016. This formulation has thus far demonstrated improved tolerability versus the prior miglyol soft gel formulation.

Patients from both Phase 1b and Phase 2 trials were assessed as of December 2, 2016 to evaluate the impact of the new SDD formulation (n=41) as compared to the prior soft gel formulation (n=50). Adverse event-related (AE-related) dose reductions occurred in 17% (7/41) of patients treated with the new SDD formulation, versus 46% (23/50) of patients treated with the prior soft gel formulation. In patients who were transitioned to the SDD formulation during their therapy (n=12), AE-related dose reductions took place in 8% (1/12) of patients versus 33% (4/12) of patients treated with the soft gel formulation.

In an initial evaluation of 24 genetically-selected patients treated with the SDD formulation of glesatinib:
11 patients were in the Phase 2 MET Exon 14 deletion mutation cohort, of whom eight were evaluable.

Eight patients were in the Phase 2 MET amplification cohort, all of whom were evaluable.

Five patients were in the Phase 1b trial with MET Exon 14 deletion mutations, who had clinical characteristics and genetic driver alterations identical to the entry criteria in the ongoing Phase 2 trial, all of whom were evaluable.

In MET Exon 14 deletion patients treated with the SDD formulation across both the Phase 1b and Phase 2 trials, glesatinib demonstrated promising activity:

In the Phase 2 trial, one confirmed partial response (PR) and two unconfirmed PRs out of the eight evaluable patients were observed. One unconfirmed PR remains on study awaiting a confirmatory scan. Tumor reduction was observed in six of eight evaluable patients.

In the Phase 1b trial, three confirmed PRs out of five evaluable patients were observed. Tumor reduction was observed in all five patients.

Overall, data in these 13 patients reflect an objective response rate (ORR) of 46% across the Phase 1b and Phase 2 patient populations, including confirmed and unconfirmed responses. Tumor reduction was observed in 11 of 13 patients.
The longest duration on study is more than 55 weeks and the patient remains on study.

In MET amplification patients treated with the SDD formulation, glesatinib also demonstrated clinical benefit:
In the Phase 2 trial, two unconfirmed PRs out of eight evaluable patients were observed. Neither of the unconfirmed responses remains on study. Tumor reduction was observed in six of eight evaluable patients.
The longest duration on study is more than 24 weeks and the patient remains on study.
The Company expects to provide an additional update on the glesatinib program in the second half of 2017.

Sitravatinib Program Update
Sitravatinib is being evaluated in a Phase 1b expansion trial designed to evaluate its safety and efficacy in multiple pre-specified cohorts of cancer patients with genetic mutations involving sitravatinib targets, including a cohort of NSCLC patients with RET fusion mutations.

As of a data cut-off of December 9, 2016, a total of six NSCLC patients with RET fusion mutations had been enrolled, four of whom were evaluable:
Of the four evaluable patients, one patient with a KIF5-B RET fusion demonstrated a confirmed PR and one patient with a DSP RET fusion has achieved an unconfirmed PR on initial scan, representing a 50% ORR, including confirmed and unconfirmed responses. Both patients remain on study. A third patient with RET fusion demonstrated tumor reduction of 29%, representing stable disease. Tumor reduction was observed in in all four patients.

The longest duration on study is more than 46 weeks and the patient remains on study.
The Phase 1b trial is also enrolling NSCLC patients with CBL mutations, CHR4q12 amplification, and AXL alterations. As of the data
cut-off date, no patients with these genetic mutations were evaluable.

Sitravatinib is also being evaluated in combination with nivolumab, a checkpoint inhibitor approved for the treatment of patients with a variety of solid tumors including NSCLC and metastatic renal cell carcinoma. Pre-clinical data indicate sitravatinib is an exceptionally potent inhibitor of the TAM (Tyro, Axl, Mer) and split (KDR, KIT) family tyrosine kinases which regulate multiple stages in the cancer immunity cycle and are thought to enhance anti-tumor immunity by improving the efficacy of checkpoint inhibitors (anti PD-1/PDL-1). The multicenter Phase 2 NSCLC trial enrolled its first patient in November 2016.
The Company expects to provide an additional update on the sitravatinib program in Q3 2017.

Mocetinostat Program Update
A Phase 1b/2 trial combining mocetinostat, an orally administered spectrum-selective Class 1 HDAC inhibitor, and durvalumab, MedImmune’s monoclonal antibody inhibiting PD-L1, continues to enroll patients with advanced solid tumors and NSCLC. The Company expects to provide an additional update on the mocetinostat program mid-year 2017.

Pre-Clinical Program Update
Two internally developed candidates are in pre-clinical development. The first is a highly-potent and potentially best-in-class LSD1 inhibitor with potential for rapid clinical proof-of-concept in small cell lung cancer or acute myeloid leukemia. An investigational new drug (IND) submission is planned for this compound in late 2017. Additionally, a mutant-selective KRAS inhibitor program is advancing to the candidate selection phase and prototype inhibitors have demonstrated marked tumor regression in KRAS mutant tumor models. An IND candidate selection is anticipated by the end of 2017.

About the glesatinib Phase 2 Trial ("AMETHYST")
AMETHYST is a multicenter, global Phase 2 trial designed to evaluate the safety and efficacy of glesatinib in NSCLC patients with MET genetic alterations who were previously treated with platinum-based chemotherapy and/or a checkpoint inhibitor.

AMETHYST pre-specified patient cohorts include NSCLC with MET Exon 14 deletion and MET amplification. Enrollment rates in the AMETHYST trial have been supported by the Company’s partnerships with molecular diagnostics companies providing commercially-available genetic testing, which have accelerated patient identification and enrollment.

On January 5, 2016 MacroGenics, Inc. (Nasdaq: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as autoimmune disorders and infectious diseases, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to MGD006 (also known as S80880), a DART molecule that recognizes both CD123 and CD3, for the investigational treatment of acute myeloid leukemia (AML) (Press release, MacroGenics, JAN 5, 2017, View Source [SID1234517281]).

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MGD006 is currently being evaluated in the U.S. and Europe in a Phase 1 dose-escalation study designed to assess the safety and tolerability of the molecule in patients with relapsed/refractory AML or myelodysplastic syndrome (MDS). MacroGenics retains full development and commercialization rights to MGD006 in the U.S., Canada, Mexico, Japan, South Korea and India. Servier participates in the development and has rights to MGD006 in all other countries.

The FDA orphan drug designation provides certain incentives for medications intended for the treatment, diagnosis or prevention of rare diseases. At present, these incentives include seven years of marketing exclusivity for the orphan indication, certain federal grants, tax credits and waiver of certain FDA fees.

"The FDA’s decision to grant orphan drug designation for MGD006 in AML is an important regulatory milestone for MacroGenics as we continue to develop this bispecific DART molecule in this difficult-to-treat disease," said Scott Koenig, M.D., Ph.D., President and Chief Executive Officer of MacroGenics. "We believe MGD006 has the potential to be a significant advancement in the treatment of AML, and are pleased that the FDA has recognized the potential of MGD006 to benefit patients in need. We expect to select a dose this year to advance MGD006 into its next phase of clinical development."

About MGD006

MGD006 is a clinical-stage molecule that recognizes both CD123 and CD3. CD123, the Interleukin-3 receptor alpha chain, has been reported to be over-expressed on cancer cells in a wide range of hematological malignancies including AML and MDS.

The primary mechanism of action of MGD006 is believed to be its ability to redirect T lymphocytes to kill CD123-expressing cells. To achieve this, the DART molecule combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123 on the target cancer cells.

In December 2016, MacroGenics presented initial clinical experience from the ongoing Phase 1 study of MGD006. Dosing schema and supportive care regimens have been refined to enable therapeutic goals and decrease the effects of cytokine induction by MGD006, an anticipated event resulting from the engagement and activation of T lymphocytes. In addition, the Company continues to characterize the pharmacokinetic properties and clinical activity of MGD006 in AML patients.

On January 5, 2017 RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company primarily focused on the development and commercialization of late clinical-stage, proprietary, orally administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, reported the signing of a new collaboration agreement with the Department of Molecular Biology and Genetics of Denmark-based Aarhus University ("AU") for the evaluation of RedHill’s Phase II-stage oncology drug candidate, MESUPRON (upamostat) (Press release, RedHill Biopharma, JAN 5, 2017, View Source [SID1234517280]).

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MESUPRON, a proprietary, first-in-class, orally administered protease inhibitor with several potential mechanisms of action to inhibit tumor invasion and metastasis, presents a new non-cytotoxic approach to cancer therapy. In 2014 RedHill acquired the exclusive worldwide development and commercialization rights to MESUPRON, excluding China, Hong Kong, Taiwan and Macao, from Germany’s WILEX AG for all indications. Wilex AG completed several clinical studies with MESUPRON for different indications, including two Phase II proof-of-concept studies, one for pancreatic cancer and one for metastatic breast cancer.

Terry Plasse, MD, RedHill’s Medical Director said: "To date, the collaboration with Aarhus University has led to findings with MESUPRON on the structure activity relationships between its active metabolite UK-1 and proteases, an established family of molecular targets with therapeutic potential in oncology indications. Previous non-clinical trials conducted in Denmark with Aarhus University have identified multiple proteases, which may be more sensitive to MESUPRON than the originally proposed target, uPA. We hope that further evaluation of MESUPRON, together with Aarhus University, will enable the optimal selection of appropriate patients toward demonstrating the activity of MESUPRON in forthcoming planned clinical trials."

The Non-clinical studies with MESUPRON are intended to support the clinical data from previous Phase I and Phase II studies, and may allow RedHill to take a precision medicine approach going forward.

About MESUPRON:
MESUPRON is a proprietary, first-in-class, orally administered protease inhibitor. Protease inhibitors, including urokinase-type plasminogen activators (uPa), have been shown to play key roles in tumor invasion and the metastasis process. High levels of certain proteases, including uPA, are associated with poor prognosis in various solid tumor cancers, such as pancreatic, gastric, breast and prostate cancers. MESUPRON presents a promising new non-cytotoxic approach to cancer therapy with several potential mechanisms of action to inhibit both tumor metastasis and growth. MESUPRON has undergone several Phase I studies and two Phase II proof-of-concept studies. The first Phase II study was in locally advanced, unresectable pancreatic cancer and the second study in metastatic breast cancer in combination with first-line chemotherapeutic agents.