On March 15, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reportred that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for erdafitinib in the treatment of urothelial cancer (Press release, Johnson & Johnson, MAR 15, 2018, View Source [SID1234524811]). Urothelial cancer, most frequently in the bladder, is the sixth most common type of cancer in the U.S.1 A Breakthrough Therapy Designation is granted to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition.2 The criteria for Breakthrough Therapy Designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.

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"For patients diagnosed with urothelial cancer, outcomes are unfortunately disheartening due to the aggressiveness of the disease," said Peter Lebowitz, MD, PhD, Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. "Through the continued development of erdafitinib, and working closely with the FDA, we look forward to bringing a potential new treatment option to patients."

The Breakthrough Therapy Designation is based on data from a multicenter, open-label Phase 2 clinical trial evaluating the efficacy and safety of erdafitinib in the treatment of adult patients with locally advanced or metastatic urothelial cancer, whose tumors have certain fibroblast growth factor receptor (FGFR) genetic alterations. The Phase 2 study BLC2001 presented at the 2018 ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium showed an overall response rate of 42 percent in 59 patients with relapsed/refractory metastatic urothelial cancer whose tumors harbored actionable FGFR mutations (ASCO-GU abstract #411).3
About Urothelial Cancer
Urothelial cancer, also known as transitional cell cancer, is the sixth most common type of cancer in the U.S.1 These cancers start in the urothelial cells that line the inside of the bladder.4 In 2018, an estimated 81,190 new cases of bladder cancer are expected, resulting in 17,240 deaths.4 For patients with metastatic disease, outcomes can be dire due to the often rapid progression of the tumor and the lack of efficacious treatments, especially in relapsed or refractory disease. The relative five-year survival rate for patients with metastatic disease is five percent.

About Erdafitinib
Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor being evaluated by Janssen in Phase 2 and 3 clinical trials in patients with advanced urothelial cancer. FGFRs are a family of receptor tyrosine kinases which may be upregulated in various tumor cell types and may be involved in tumor cell differentiation and proliferation, tumor angiogenesis, and tumor cell survival.5 In 2008, Janssen entered into an exclusive worldwide license and collaboration agreement with Astex Therapeutics Ltd. to develop and commercialize erdafitinib.

On March 15, 2018 ArQule, Inc. (Nasdaq: ARQL) reported that pre-clinical and clinical data on the company’s pipeline of drug candidates will be presented at the 2018 AACR (Free AACR Whitepaper) Annual Meeting taking place in Chicago from April 14-April 18 (Press release, ArQule, MAR 15, 2018, View Source [SID1234524791]). Data will be presented in one oral and nine poster sessions on trials conducted by ArQule and its collaborators for BTK inhibitor, ARQ 531, AKT inhibitors, miransertib and ARQ 751, as well as FGFR inhibitor, derazantinib.

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The oral presentation will highlight data from a phase 1b trial for miransertib in combination with anastrozole in PIK3CA or AKT1-mutant endometrial and ovarian cancers conducted by Dr. David M. Hyman and colleagues at Memorial Sloan Kettering.

Oral Presentation Details

April 15, 2018

Title:A phase 1b study of Miransertib (ARQ 092) in combination with anastrozole in patients with PIK3CA or AKT1-mutant ER+ endometrial and ovarian cancer
Time: 3:00 – 5:00 p.m. CT
Location:Room N427 – McCormick Place North, Level 4
Sponsor: Memorial Sloan Kettering, New York, NY

Poster Presentation Details

April 15, 2018

Title:ARQ 531, a Novel and Reversible Inhibitor of Bruton’s Tyrosine Kinase, Displays Favorable Oral Bioavailability and Exposure in patients with B-cell malignancies
Time: 1:00 – 5:00 p.m. CT
Location: Exhibit Hall A, Poster Section 43, Poster Board 18
Sponsor:ArQule, Inc.

Title:The novel Bruton’s tyrosine kinase inhibitor ARQ 531 disrupts survival signaling and triggers apoptosis in AML cells
Time: 1:00 – 5:00 p.m. CT
Location: Exhibit Hall A, Poster Section 37, Poster Board 3
Sponsor:University of Genoa, Genova, Italy

Title:Results of A Phase 1 Dose Escalation Study of ARQ 751 in Adult Subjects with Advanced Solid Tumors with AKT1, 2, 3 Genetic Alterations, Activating PI3K Mutations, PTEN-null, or other known actionable PTEN mutations
Time: 1:00 – 5:00 p.m. CT
Location: Exhibit Hall A, Poster Section 42, Poster Board 17
Sponsor:MD Anderson Cancer Center, Houston, TX

April 16, 2018

Title:ARQ 531, a potent reversible BTK inhibitor exhibits potent antitumor activity in ibrutinib resistant diffuse large B-cell lymphoma
Time:8:00 a.m. – 12:00 p.m. CT
Location: Exhibit Hall A, Poster Section 41, Poster Board 8
Sponsor:ArQule, Inc.

Title:Preclinical Evaluation of the Tyrosine Kinase Inhibitor ARQ531 in AML
Time:8:00 a.m. – 12:00 p.m. CT
Location: Exhibit Hall A, Poster Section 38, Poster Board 13
Sponsor: The Ohio State University, Columbus OH

Title: In vivo combination of Miransertib (ARQ 092) with anti-PD-1 antibody, Trametinib, Lapatinib, Trastuzumab and Paclitaxel
Time:1:00 p.m. – 5:00 p.m. CT
Location: Exhibit Hall A, Poster Section 41, Poster Board 23
Sponsor:ArQule, Inc.

April 17, 2018

Title:Derazantinib (ARQ 087) Pharmacodynamics: Alterations in FGF19/21/23 and phosphate in Patients with Cholangiocarcinoma
Time:8:00 a.m. – 12:00 p.m. CT
Location: Exhibit Hall A, Poster Section 43, Poster Board 22
Sponsor:ArQule, Inc.

Title:In vitro and in vivo effect of ARQ 531 on Trk family kinases
Time:1:00 p.m. – 5:00 p.m. CT
Location: Exhibit Hall A, Poster Section 36, Poster Board 26
Sponsor:ArQule, Inc.

Title:Combinations of imatinib mesylate with AKT inhibitor (Miransertib, ARQ 751) or FGFR inhibitor (Derazantinib) show synergy in GIST cell lines and pre-clinical models
Time:1:00 p.m. – 5:00 p.m. CT
Location: Exhibit Hall A, Poster Section 37, Poster Board 7
Sponsor:Fox Chase Cancer Center, Philadelphia, PA

About Miransertib and ARQ 751

Miransertib (ARQ 092) and ARQ 751 are orally bioavailable, selective small molecule inhibitors of the AKT serine/threonine kinase. The AKT pathway when abnormally activated is implicated in multiple oncogenic processes such as cell proliferation and apoptosis. This pathway has emerged as a target of potential therapeutic relevance for compounds that inhibit its activity, which has been linked to a variety of cancers as well as to select non-oncology indications.

Miransertib, the lead compound in ArQule’s AKT program, has completed phase 1a clinical testing and has advanced into phase 1b expansion testing in cohorts of patients with endometrial cancer, lymphomas and tumors harboring either AKT or PI3K mutations. A company sponsored phase 1/2 trial is being conducted in the U.S. and E.U. for Overgrowth Diseases, including PROS and Proteus syndrome. Miransertib is also in a phase 1 trial being conducted by the NIH for Proteus syndrome.

About ARQ 531

ARQ 531 is an investigational, orally bioavailable, potent and reversible Bruton’s tyrosine kinase (BTK) inhibitor. Biochemical and cellular studies have shown that ARQ 531 inhibits both the wild type and C481S-mutant forms of BTK. The C481S mutation is a known emerging resistance mechanism for first generation irreversible BTK inhibitors. In preclinical studies ARQ 531 has demonstrated high oral bioavailability as well as good ADME, pharmacokinetic and metabolic properties. The Company initiated a phase 1 trial in the third quarter of 2017. BTK is a therapeutic target that has been clinically proven to inhibit B-cell receptor signaling in blood cancers.

About Derazantinib

Derazantinib is a potent, orally administered inhibitor of the fibroblast growth factor receptor (FGFR) family, a key driver of cell proliferation, differentiation, and migration. In a Phase 1/2 study in patients with iCCA harboring FGFR2 gene fusions, treatment with derazantinib resulted in an objective response rate of 21%, nearly 3 times higher than standard-of-care chemotherapy. ArQule is currently conducting a registrational study with derazantinib in patients with FGFR2 fusion-positive second-line iCCA. The open-label single-arm trial is recruiting in both the United States and Europe with objective response rate as the primary endpoint.

On March 15, 2018 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ:APTO) (TSX:APS), a clinical-stage company developing highly differentiated therapeutics targeting the underlying mechanisms of cancer, reported that preclinical data for CG’806, its pan-FLT3/pan-BTK inhibitor, and APTO-253, its c-Myc inhibitor, will be presented in three separate posters at the 2018 AACR (Free AACR Whitepaper) Annual Meeting in Chicago, Il (Press release, Aptose Biosciences, MAR 15, 2018, View Source;p=RssLanding&cat=news&id=2338208 [SID1234524790]).

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CG’806 Poster Presentation Details

CG’806, a first-in-class pan-FLT3/pan-BTK inhibitor, demonstrates superiority to other FLT3 and BTK inhibitors against primary patient samples
Date & Time: Sunday, April 15, 2018, 1:00 p.m. – 5:00 p.m.
Session Category: Experimental and Molecular Therapeutics
Session Title: Experimental Agents and Combinations for Hematologic Malignancies 1
Abstract Number: 4316
Location: McCormick Place South, Exhibit Hall A, Poster Section 37

CG’806, a first-in-class pan-FLT3/pan-BTK inhibitor, targets multiple pathways to kill diverse subtypes of acute myeloid leukemia and Bcell malignancy in vitro
Date & Time: Sunday, April 15, 2018, 1:00 p.m. – 5:00 p.m.
Session Title: Experimental Agents and Combinations for Hematologic Malignancies 1
Abstract Number: 4239
Location: McCormick Place South, Exhibit Hall A, Poster Section 37

APTO-253 Poster Presentation Details

APTO-253 is a new addition to the repertoire of drugs that can exploit DNA BRCA1/2 deficiency
Date & Time: Tuesday, April 17, 2018, 1:00 p.m. – 5:00 p.m.
Session Title: DNA Damage and Cell Cycle Regulation Experimental Therapeutics
Abstract Number: 2138
Location: McCormick Place South, Exhibit Hall A, Poster Section 38

All abstracts will be available on the AACR (Free AACR Whitepaper) website, www.aacr.org, and published in the 2018 Proceedings of the AACR (Free AACR Whitepaper).

About CG’806
CG‘806 is an oral, first-in-class pan-FLT3/pan-BTK multi-kinase inhibitor. This small molecule demonstrates potent inhibition of wild type and mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates acute myeloid leukemia (AML) tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting CG’806 may be developed for various B cell malignancy patients (including CLL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent BTK inhibitors. CG’806 is currently in pre-clinical development in partnership with CrystalGenomics.

About APTO-253
APTO-253 is a clinical-stage small molecule targeted therapeutic agent that inhibits expression of the c-Myc oncogene, leading to cell cycle arrest and programmed cell death (apoptosis) in human-derived solid tumor and hematologic cancer cells, without causing general myelosuppression of the healthy bone marrow. The c-Myc oncogene is overexpressed in hematologic cancers, including acute myeloid leukemia (AML). Aptose researchers have reported the ability of APTO-253 to induce cell death, or apoptosis, in multiple blood cancer cell lines including AML, as well as in vitro synergy with various classes of conventional approved and investigational therapies for AML or myelodysplastic syndromes (MDS).

On March 15, 2018 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer reported three partial responses (two confirmed and one to be confirmed), and one stable disease in the first four patients dosed with NY-ESO SPEAR T-cells in a second solid tumor: myxoid/ round cell liposarcoma (MRCLS) (Press release, Adaptimmune, MAR 15, 2018, View Source;p=RssLanding&cat=news&id=2338212 [SID1234524789]). Patients tolerated treatment well with cytokine release syndrome (CRS) managed following standard treatment guidelines. GlaxoSmithKline plc (LSE:GSK) (NYSE:GSK) exercised its option to exclusively license the right to research, develop, and commercialize NY‑ESO SPEAR T-cell therapy program in September 2017. Transition of this program to GSK is ongoing.

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"We are encouraged by the initial responses seen in the first patients with MRCLS treated with NY-ESO SPEAR T-cells, as it validates the potential of our platform to treat a broad range of tumors, including those that are known to be unresponsive to current immunotherapies," said Rafael Amado, Adaptimmune’s Chief Medical Officer. "Although MRCLS is a soft tissue sarcoma which commonly expresses NY-ESO, there are fundamental differences in its clinical course, natural history, molecular signature, and responsiveness to standard treatments that make it distinct from synovial sarcoma. As we expect data from our other trials with our wholly owned assets throughout 2018, these results in a second solid tumor strengthen our conviction that our pipeline of unique TCRs will be capable of addressing multiple solid tumors."

More about Soft Tissue Sarcomas:
MRCLS and synovial sarcoma are both considered soft tissue sarcomas. MRCLS is a type of liposarcoma, characterized by the proliferation of adipocyte (fat cell) precursors called lipoblasts that have undergone differentiation arrest. This malignancy arises from a translocation between chromosomes 12 and 16 resulting in a fusion protein that blocks adipocyte differentiation and promotes malignant transformation. Synovial sarcoma is characterized by a different chromosomal translocation involving the X chromosome and chromosome 18 and, unlike the known immature fat cell cellular origin of MRCLS, the cell of origin for synovial sarcoma remains unknown.

It is estimated that there are approximately 2000 patients in the United States and Europe with MRCLS each year. MRCLS has a peak incidence of occurrence in patients who are 30 to 50 years of age and it typically follows a more aggressive course than other liposarcomas. MRCLS also exhibits a unique metastatic pattern arising first in the proximal areas of the extremities and typically spreading to the bones (particularly the spine), serosal surfaces, retroperitoneum, abdomen, pelvis, as well as to other soft tissues. This metastatic pattern is different from the characteristic pulmonary spread exhibited by synovial sarcoma.

Conference Call Information:
The company will host a live teleconference and webcast today at 8:00 a.m. EDT (12:00 p.m. GMT) at which time management will provide a business update, including these recent clinical data, and discuss financial results for the Fourth Quarter / Full Year 2017. The press release and the live webcast of the conference call will be available in the investor section of Adaptimmune’s corporate website at www.adaptimmune.com. An archive will be available after the call at the same address.

To participate in the live conference call, if preferred, please dial 1-800-239-9838 (U.S.) or 44(0)330 336 9411 or 0800 279 7204 (United Kingdom). After placing the call, please ask to be joined into the Adaptimmune conference call and provide the confirmation code (5199507).

On March 15, 2018 ArQule, Inc. (Nasdaq: ARQL) reported that pre-clinical and clinical data on the company’s pipeline of drug candidates will be presented at the 2018 AACR (Free AACR Whitepaper) Annual Meeting taking place in Chicago from April 14-April 18 (Press release, , MAR 15, 2018, View Source [SID1234524785]). Data will be presented in one oral and nine poster sessions on trials conducted by ArQule and its collaborators for BTK inhibitor, ARQ 531, AKT inhibitors, miransertib and ARQ 751, as well as FGFR inhibitor, derazantinib.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The oral presentation will highlight data from a phase 1b trial for miransertib in combination with anastrozole in PIK3CA or AKT1-mutant endometrial and ovarian cancers conducted by Dr. David M. Hyman and colleagues at Memorial Sloan Kettering.

Oral Presentation Details

April 15, 2018

Title: A phase 1b study of Miransertib (ARQ 092) in combination with anastrozole in patients with PIK3CA or AKT1-mutant ER+ endometrial and ovarian cancer
Time: 3:00 – 5:00 p.m. CT
Location: Room N427 – McCormick Place North, Level 4
Sponsor: Memorial Sloan Kettering, New York, NY

Poster Presentation Details

April 15, 2018

Title: ARQ 531, a Novel and Reversible Inhibitor of Bruton’s Tyrosine Kinase, Displays Favorable Oral Bioavailability and Exposure in patients with B-cell malignancies
Time: 1:00 – 5:00 p.m. CT
Location: Exhibit Hall A, Poster Section 43, Poster Board 18
Sponsor: ArQule, Inc.

Title: The novel Bruton’s tyrosine kinase inhibitor ARQ 531 disrupts survival signaling and triggers apoptosis in AML cells
Time: 1:00 – 5:00 p.m. CT
Location: Exhibit Hall A, Poster Section 37, Poster Board 3
Sponsor: University of Genoa, Genova, Italy

Title: Results of A Phase 1 Dose Escalation Study of ARQ 751 in Adult Subjects with Advanced Solid Tumors with AKT1, 2, 3 Genetic Alterations, Activating PI3K Mutations, PTEN-null, or other known actionable PTEN mutations
Time: 1:00 – 5:00 p.m. CT
Location: Exhibit Hall A, Poster Section 42, Poster Board 17
Sponsor: MD Anderson Cancer Center, Houston, TX

April 16, 2018

Title: ARQ 531, a potent reversible BTK inhibitor exhibits potent antitumor activity in ibrutinib resistant diffuse large B-cell lymphoma
Time: 8:00 a.m. – 12:00 p.m. CT
Location: Exhibit Hall A, Poster Section 41, Poster Board 8
Sponsor: ArQule, Inc.

Title: Preclinical Evaluation of the Tyrosine Kinase Inhibitor ARQ531 in AML
Time: 8:00 a.m. – 12:00 p.m. CT
Location: Exhibit Hall A, Poster Section 38, Poster Board 13
Sponsor: The Ohio State University, Columbus OH

Title: In vivo combination of Miransertib (ARQ 092) with anti-PD-1 antibody, Trametinib, Lapatinib, Trastuzumab and Paclitaxel
Time: 1:00 p.m. – 5:00 p.m. CT
Location: Exhibit Hall A, Poster Section 41, Poster Board 23
Sponsor: ArQule, Inc.

April 17, 2018

Title: Derazantinib (ARQ 087) Pharmacodynamics: Alterations in FGF19/21/23 and phosphate in Patients with Cholangiocarcinoma
Time: 8:00 a.m. – 12:00 p.m. CT
Location: Exhibit Hall A, Poster Section 43, Poster Board 22
Sponsor: ArQule, Inc.

Title: In vitro and in vivo effect of ARQ 531 on Trk family kinases
Time: 1:00 p.m. – 5:00 p.m. CT
Location: Exhibit Hall A, Poster Section 36, Poster Board 26
Sponsor: ArQule, Inc.

Title: Combinations of imatinib mesylate with AKT inhibitor (Miransertib, ARQ 751) or FGFR inhibitor (Derazantinib) show synergy in GIST cell lines and pre-clinical models
Time: 1:00 p.m. – 5:00 p.m. CT
Location: Exhibit Hall A, Poster Section 37, Poster Board 7
Sponsor: Fox Chase Cancer Center, Philadelphia, PA

About Miransertib and ARQ 751

Miransertib (ARQ 092) and ARQ 751 are orally bioavailable, selective small molecule inhibitors of the AKT serine/threonine kinase. The AKT pathway when abnormally activated is implicated in multiple oncogenic processes such as cell proliferation and apoptosis. This pathway has emerged as a target of potential therapeutic relevance for compounds that inhibit its activity, which has been linked to a variety of cancers as well as to select non-oncology indications.

Miransertib, the lead compound in ArQule’s AKT program, has completed phase 1a clinical testing and has advanced into phase 1b expansion testing in cohorts of patients with endometrial cancer, lymphomas and tumors harboring either AKT or PI3K mutations. A company sponsored phase 1/2 trial is being conducted in the U.S. and E.U. for Overgrowth Diseases, including PROS and Proteus syndrome. Miransertib is also in a phase 1 trial being conducted by the NIH for Proteus syndrome.