On September 24, 2018 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported updated results from the ongoing ENCORE 601 cohort enrolling non-small cell lung cancer (NSCLC) patients previously treated with both chemotherapy and PD-(L)1 therapy (Press release, Syndax, SEP 24, 2018, View Source [SID1234529562]). The oral presentation titled, "Efficacy/Safety of Entinostat (ENT) and Pembrolizumab (PEMBRO) in NSCLC Patients Previously Treated with Anti-PD-(L)1 Therapy," was presented by Matthew D. Hellman, M.D., study investigator and medical oncologist at Memorial Sloan Kettering Cancer Center, at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer (WCLC) in Toronto, Canada. A copy of the presentation is available via the Syndax website at View Source

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 observation of durable responses seen with the entinostat-pembrolizumab combination in NSCLC patients previously treated with both chemotherapy and PD-(L)1 therapy is an important result, and we look forward to more fully characterizing patient selection tools to identify those who are most likely to respond," said Peter Ordentlich, Ph.D., Syndax co-founder and Chief Scientific Officer. "The exploratory finding that baseline peripheral classical monocytes may predict clinical benefit to the combination provides an opportunity to potentially correlate a readily measurable circulating biomarker with the state of the tumor microenvironment and supports the use of this approach for patient selection in future studies."

The Company previously presented a subset of data from the first 57 patients in the Phase 2 ENCORE 601 NSCLC cohort, which enrolled patients whose disease had progressed after prior chemotherapy and anti-PD-(L)1 treatment, at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting this past June. The updated data set presented today includes data from all 76 patients who enrolled in this cohort prior to the close of enrollment in December 2017, and highlights the durability of the observed responses independent of prior treatment history or PD-(L)1 status. At the time of data cut-off, there were 7 confirmed partial responses (PRs) among the overall population of 72 efficacy-evaluable patients, for a 10% objective response rate (ORR) (95% CI: 4-19%), a median duration of response of 5.3 months, and a median progression free survival (PFS) of 2.8 months. The results did not meet the prespecified ORR endpoint. Six of the 7 responders had low or negative PD-(L)1 expression at study entry. At the time of data cut-off, 6 patients remain on study. Updated data continue to demonstrate a manageable toxicity profile for the entinostat-pembrolizumab combination, with treatment emergent adverse events observed consistent with those previously reported.

Exploratory analysis of baseline biomarkers in the fully enrolled cohort supports the previous observation from the first 57 patients that elevated pre-treatment baseline levels of peripheral classical blood monocytes (CD14+CD16-HLA-DRhi) are associated with enhanced clinical benefit to the entinostat-pembrolizumab combination. Baseline peripheral classical monocyte data were available for 65 of the 72 NSCLC patients evaluable for efficacy and were divided into a group of high baseline monocytes ("monocyte high" n = 19) and low baseline monocytes ("monocyte low" n = 46). The monocyte high subset showed an improved median PFS (5.3 months vs 2.7 months), and an enhanced ORR (21% vs 7%), with 5 of 19 (26%) patients remaining on study compared to only 1 of 46 (2%) in the monocyte low group.

"We continue to remain encouraged by the consistent observation of enhanced clinical benefit in the subgroup of patients who failed prior PD-1 treatment and had high baseline levels of classical peripheral monocytes, a population for whom novel therapies are needed," said Briggs Morrison, M.D., Chief Executive Officer of Syndax. "We recognize the importance of identifying patients more likely to respond to treatment and believe that our updated classical monocyte dataset strengthens the rationale for further validation of this patient selection biomarker. We look forward to communicating our plans for entinostat in this indication in the fourth quarter."

E2112 Update

Syndax also announced today that ECOG-ACRIN Cancer Research Group has informed the Company that enrollment in the ongoing E2112 Phase 3 registration trial of entinostat plus exemestane in advanced hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+, HER2-) breast cancer is now scheduled to close in late October. The Company will release the results of the PFS analysis following its review, and anticipates communicating this in the fourth quarter. The trial remains ongoing, with interim overall survival (OS) analyses scheduled to occur every May and November until either the appropriate number of events are achieved or definitive interim results are obtained.

About Entinostat

Entinostat is a selective, oral, once-weekly inhibitor of class 1 HDACs, currently being evaluated in a pivotal Phase 3 clinical trial (E2112) in combination with exemestane for advanced hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer, an indication for which it has been granted Breakthrough Therapy Designation by the FDA. Entinostat has also been shown to block the function of immune suppressive cells in the tumor microenvironment, and is being evaluated in combination with several approved PD-1/PD-L1 antagonists, including in ongoing Phase 2 clinical trials combining entinostat with KEYTRUDA from Merck & Co., Inc. for non-small cell lung cancer, melanoma and colorectal cancer (ENCORE 601); with TECENTRIQ from Genentech, Inc. for triple negative breast cancer as well as advanced hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer (ENCORE 602); and with BAVENCIO from Pfizer Inc. and Merck KGaA, Darmstadt, Germany, for ovarian cancer (ENCORE 603).

On September 24, 2018 TP Therapeutics, a privately held, clinical-stage biopharmaceutical company developing oncology therapies with a focus on addressing drug resistance, reported its updated interim data as of July 13, 2018 from its ongoing Phase 1/2 TRIDENT-1 study of Repotrectinib (TPX-0005) in ROS1 fusion-positive non-small-cell lung cancer (NSCLC) patients (Press release, TP Therapeutics, SEP 24, 2018, View Source [SID1234529542]).

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!

"Additional follow-up of patients treated with Repotrectinib continues to demonstrate a meaningful and durable clinical benefit, with potency against difficult mutations that often drive resistance to this class of therapeutics," said Alice Tsang Shaw, MD, PhD, Professor of Medicine, Harvard Medical School; Director of Thoracic Oncology, Massachusetts General Hospital; and an Investigator in the TRIDENT-1 study. "These early data, now supported by Blinded Independent Central Review, are encouraging in both TKI-naïve and TKI-pretreated NSCLC patients with the ROS1 fusion oncogene."

Repotrectinib is an investigational next-generation tyrosine kinase inhibitor (TKI) designed to effectively target ROS1, TRKA-C and ALK kinases, and also clinical resistance kinase domain mutations. ROS1 rearrangement is an oncogenic driver of tumors in up to 2.6 percent of U.S. NSCLC patients.

As of the July 13, 2018 data cut-off, the study findings showed:

A total of 72 patients (31 ALK+; 33 ROS1+; and 8 NTRK+ by local test) with advanced cancers had been treated across 6 dose levels (40 mg QD; 80 mg QD; 160 mg QD; 240 mg QD; 160 mg BID; and 200 mg BID), which comprises the safety population for the current dataset
A total of 30 patients treated across the first 5 dose escalation cohorts with ROS1+ NSCLC were in the efficacy evaluable population, of which 27 were evaluable by Blinded Independent Central Review (BICR)
Within the efficacy evaluable population of ROS1+ NSCLC, the median age was 52 years (range 30 – 75), with 53% of patients having CNS metastases at baseline; the median number of prior TKI therapies (majority of which were crizotinib) was 1 (range 0 to 3).
Preliminary Safety Analysis (n=72)

Repotrectinib was generally well tolerated, with the most frequent treatment-related adverse events (TRAEs >15%) including dizziness (50%); dysgeusia (45.8%); paraesthesia (29.2%); constipation (19.4%); and fatigue (18.1%); the majority of TRAEs are Grade 1-2, and the Grade 3 TRAEs include 2.8% dizziness and 4.2% anemia
The vast majority (31/36 cases, 86%) of dizziness were Grade 1 and there have been no cases of dizziness that have led to treatment discontinuation
As of the data cut-off date, there have been no Grade 4 TRAEs
Four dose-limiting toxicities (DLTs) were observed: Grade 2 or 3 dizziness (n=3: 2 at 160 mg BID; 1 at 240 mg QD) that resolved upon dose reduction; and Grade 3 dyspnea/hypoxia (n=1 at 160 mg BID) that resolved after study drug discontinuation
Neither the maximum tolerated dose (MTD) nor the recommended Phase 2 dose (RP2D) has been reached
Preliminary Efficacy Analysis (n=27)

As of the data cutoff, 27 ROS1+ NSCLC patients were evaluable for tumor response by BICR
Of the 27 patients, 10 were TKI-naïve and 17 were previously treated with at least one ROS1 TKI therapy
Fifteen of 27 patients (56%) remained on treatment
The primary reason for treatment discontinuation was progression (radiologic or clinical, n=9), with 1 patient each discontinuing for withdraw of consent, investigator decision, and adverse event (DLT of Grade 3 dyspnea/hypoxia at 160 mg BID)
TKI-Naïve Efficacy Analysis (n=10)

A confirmed overall response (ORR) by BICR analysis based on RECIST v1.1 was achieved in 8 of 10 patients (80%; CI 44-97), with a median time to response of 1.6 months (1.4-3.3). Confirmed responses were achieved across all 5 doses tested to date within dose escalation
The Intracranial ORR was 100 percent with 3 of 3 patients with measurable CNS disease achieving a confirmed response (CI 29-100). All 3 patients who achieved an intracranial response also achieved an extracranial response
The overall clinical benefit rate was 100 percent, with all 10 patients achieving stable disease for at least two cycles or a confirmed partial response
Of the 8 patients who achieved a confirmed response, 5 continue to maintain their response (3.7+ – 11.1+ months)
TKI-Pretreated Efficacy Analysis (n=17)

Across 5 dose escalation cohorts, a confirmed ORR was achieved in 3 patients (3/17, 18%; CI 4-44), with a median time to response of 1.6 months (1.5-1.8) with 2 of 3 responses occurring at the 160 mg QD dose level
All 3 responses were achieved in patients treated with 1 prior TKI (3/13, 23%) and duration of the responses were 11.1+ months; 7.4 months; and 1 patient who was censored at the time of their last tumor assessment as they withdrew consent while remaining in response
Intracranial ORR was achieved in 1 of 4 patients (25%)
Of importance, the overall clinical benefit rate was 76 percent (95% CI: 56-97) with 13 of 17 patients achieving stable disease for at least 2 cycles or a confirmed partial response
With respect to baseline plasma cell-free DNA (cfDNA), 16 of 17 TKI-pretreated patients had plasma samples evaluated at baseline
Four crizotinib-pretreated patients were identified as having a ROS1 solvent front G2032R mutation at baseline. All 4 patients had tumor regressions on Repotrectinib including 1 confirmed partial response of 7.4 months achieved at the 160 mg QD dose level. This patient remained on treatment for 11+ months at the time of the data cut-off.
"We are very pleased with the updated Phase 1 preliminary data, which continue to demonstrate the strong activity of Repotrectinib in both TKI-naïve and TKI-pretreated patients with ROS1+ NSCLC since our initial data presentation in June," said Athena Countouriotis, M.D., Executive Vice President and Chief Medical Officer of TP Therapeutics. "We continue to enroll patients in additional dosing cohorts, and look forward to determining the recommended Phase 2 dose and discussing our path to registration with health authorities. We plan to begin the Phase 2 portion of the TRIDENT-1 study as soon as a RP2D is identified with the goal of bringing a potential new treatment option to patients in this area of high unmet need."

The data were presented earlier today by Jessica J. Lin, M.D., Massachusetts General Hospital Cancer Center, in an oral presentation at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer in Toronto.

Initial preliminary data from the ongoing Phase 1 portion of the TRIDENT-1 study were presented in June 2018 at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper). In addition, the preclinical and clinical proof-of-concept data for Repotrectinib were recently published in the journal Cancer Discovery (The Cancer Discovery article may be found online at: View Source).

About Repotrectinib (TPX-0005)

Repotrectinib (TPX-0005) is a potent and orally bioavailable investigational small molecule kinase inhibitor for ALK, ROS1, and TRK family. The clinical benefits of targeting ALK, ROS1, or TRK fusion kinase have been demonstrated with multiple kinase inhibitors already approved for the treatment of ALK+ non-small cell lung cancer (NSCLC), in addition to crizotinib for ROS1+ NSCLC, and larotrectinib and entrectinib in clinical studies for TRK+ cancers. The successes of these therapies are overshadowed by the development of acquired resistance. The acquired solvent front mutations including ALK G1202R, ROS1 G2032R, TRKA G595R and TRKC G623R render a common clinical resistance to the current ALK, ROS1, and TRK inhibitors.

Repotrectinib has demonstrated potency against wildtype and mutated ALK, ROS1 and TRK family kinases, especially the clinically significant solvent front mutations, gatekeeper mutations, and emerging compound mutations after multiple line treatments. Repotrectinib may provide a new opportunity to inhibit the abnormal signaling of ALK, ROS1, or TRK family in solid malignancies, and overcome multiple resistance mechanisms seen in refractory patients. Repotrectinib is currently being evaluated in a Phase 1/2, open-label, multi-center, first-in-human study of the safety, tolerability, pharmacokinetics and anti-tumor activity in patients with advanced solid tumors harboring ALK, ROS1, or NTRK1-3 rearrangements TRIDENT-1 study (www.clinicaltrial.gov number NCT03093116). Interested patients and physicians can also contact the TP Therapeutics Oncology Clinical Trial Hotline at 1-858-276-0005 or email [email protected].

1Note: TPX-0005 had an initial generic name of "ropotrectinib," which was later changed to repotrectinib and is now the accepted name by USAN and WHO INN.

On September 24, 2018 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development and commercialization of innovative therapeutics for the treatment of cancer, reported a change in leadership with the appointment of James E. Dentzer as President and Chief Executive Officer effective immediately Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development and commercialization of innovative therapeutics for the treatment of cancer, reported a change in leadership with the appointment of James E. Dentzer as President and Chief Executive Officer effective immediately. In addition, Mr. Dentzer will become a member of the Curis Board of Directors. He replaces Ali Fattaey, Ph.D., who is leaving the Company.

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!

Mr. Dentzer, who joined Curis in 2016, was promoted earlier this year to Chief Operating Officer to manage all functions outside of research and development, including business development, manufacturing, quality, human resources, finance, legal, IT, and investor and public relations. Mr. Dentzer is also leading the pre-commercial strategic planning for fimepinostat, which received Fast Track designation from the FDA earlier this year for the treatment of patients with Relapsed/Refractory DLBCL.

"The Curis board of directors appreciates the contributions of Dr. Fattaey in transforming Curis into a development-focused company with a pipeline of clinical-stage assets," said Martyn D. Greenacre, the Company’s Chairman. "We wish the best for Ali, who was key in the recruitment of Jim to Curis two years ago. As Chief Operating Officer, Jim has been a driver of the business operations of the Company, while bringing important perspective to the development of Curis’s strategic plan. Looking forward, we believe he is best positioned to lead Curis as we seek to progress our three high-value programs quickly and successfully through the clinic."

Mr. Dentzer brings more than 25 years of experience, including executive leadership roles at Dicerna Pharmaceuticals, Amicus Therapeutics, Valeritas, and Biogen. Mr. Dentzer earned a BA in philosophy from Boston College and MBA from the University of Chicago’s Booth School of Business.

. In addition, Mr. Dentzer will become a member of the Curis Board of Directors. He replaces Ali Fattaey, Ph.D., who is leaving the Company.

Mr. Dentzer, who joined Curis in 2016, was promoted earlier this year to Chief Operating Officer to manage all functions outside of research and development, including business development, manufacturing, quality, human resources, finance, legal, IT, and investor and public relations. Mr. Dentzer is also leading the pre-commercial strategic planning for fimepinostat, which received Fast Track designation from the FDA earlier this year for the treatment of patients with Relapsed/Refractory DLBCL.

"The Curis board of directors appreciates the contributions of Dr. Fattaey in transforming Curis into a development-focused company with a pipeline of clinical-stage assets," said Martyn D. Greenacre, the Company’s Chairman. "We wish the best for Ali, who was key in the recruitment of Jim to Curis two years ago. As Chief Operating Officer, Jim has been a driver of the business operations of the Company, while bringing important perspective to the development of Curis’s strategic plan. Looking forward, we believe he is best positioned to lead Curis as we seek to progress our three high-value programs quickly and successfully through the clinic."

Mr. Dentzer brings more than 25 years of experience, including executive leadership roles at Dicerna Pharmaceuticals, Amicus Therapeutics, Valeritas, and Biogen. Mr. Dentzer earned a BA in philosophy from Boston College and MBA from the University of Chicago’s Booth School of Business.

On September 24, 2018 OncoMed Pharmaceuticals, Inc. (NASDAQ:OMED), a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer therapeutics, reported that John Lewicki, Ph.D., President and Chief Executive Officer of OncoMed, will present a corporate update at the 2018 Cantor Global Healthcare Conference in New York, NY on Monday, October 1, 2018 at 5:15 pm Eastern Time (Press release, OncoMed, SEP 24, 2018, View Source [SID1234529671]).

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!

To access the live webcast and subsequent archived recording of this presentation, or other company presentations, please visit OncoMed’s website at www.oncomed.com/invest/events.cfm. A replay will be available for 30 days following the date of the event.

On September 24, 2018 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that the following presentations by Company management at upcoming investor conferences will be webcast (Press release, ImmunoGen, SEP 24, 2018, View Source [SID1234529543]):

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!

2018 Cantor Global Healthcare Conference
October 2 at 2:50pm ET
Leerink Partners Roundtable Series
October 3 at 9:30am ET
A webcast of each presentation will be accessible live through the "Investors" section of the Company’s website, www.immunogen.com; a replay will be available in the same location for approximately two weeks.