On May 17, 2018 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology, and its research collaborator, Ospedale San Raffaele (OSR), presented at the 21st Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) the first update on their joint discovery and development efforts of Wilms’ Tumor 1 (WT1)-specific transgenic T cells (Press release, Intellia Therapeutics, MAY 17, 2018, View Source [SID1234526747]). In conjunction with this presentation, Intellia reported that its first cell therapy target is WT1 for the treatment of acute myeloid leukemia and other potential hematological malignancies, as well as for solid tumors.

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!

"As Intellia expands its wholly owned T cell therapy ex vivo efforts, we are pleased to present our first set of data in this cell therapy area," said Intellia President and Chief Executive Officer John Leonard, M.D. "WT1 is over-expressed in many tumor types, including both leukemias and solid tumors, and is an ideal target for immuno-oncological therapies seeking to treat these malignancies. This early data being presented is part of Intellia’s broader strategy to develop next-generation solutions for immuno-oncology and autoimmune disorders, with novel, modular platforms based on genome editing."

Intellia and OSR are collaborating to develop best-in-class CRISPR-edited T cells directed to WT1, a tumor-associated antigen expressed across a wide range of different tumor types and a known driver of leukocyte blasts in hematological cancers. At this year’s ASGCT (Free ASGCT Whitepaper) Annual Meeting, OSR researchers, led by Chiara Bonini, M.D., Ph.D., shared findings showing the generation, characterization and advancement of WT1-specific, transgenic T cells against multiple WT1 epitopes presented on HLA-A*02:01 and other Class I alleles. Initial data demonstrating both recognition and killing of acute myeloid leukemia cells also was presented.

OSR researchers and Intellia presented the poster, entitled "Hunting WT1-Specific T Cell Receptors for TCR Gene Editing for Acute Myeloid Leukemia." The abstract is available on the ASGCT (Free ASGCT Whitepaper) website here.

"Our collaboration with Intellia represents our shared belief that the characteristics of T cell receptors as a targeting moiety may be an excellent approach to broadening the field of oncology cell therapy, opening the door to many more potential antigen targets in liquid and solid tumors," added Bonini, full professor at Università Vita-Salute San Raffaele; deputy director, Division of Immunology, Transplantation and Infectious Diseases; and head, Experimental Hematology Unit, Ospedale San Raffaele, Italy.

This ex vivo research effort is part of an integrated strategy to develop CRISPR-edited T cell therapies to address hard-to-treat cancers and overcome certain limitations of current-generation cell therapies, includin

On May 17, 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 multiple cohorts of the ongoing Phase 2 ENCORE 601 trial of entinostat in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 (programmed death receptor-1) therapy (Press release, Syndax, MAY 17, 2018, View Source [SID1234526765]). This data will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held June 1-5, 2018 in Chicago, Illinois.

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!

ENCORE 601 is a Phase 1b/2 trial evaluating the efficacy and safety of entinostat in combination with pembrolizumab across multiple cohorts of PD-(L)1 treatment-naïve and pretreated cancers, including non-small cell lung cancer (NSCLC), melanoma and microsatellite stable colorectal cancer (MSS-CRC). Confirmed objective responses with the combination regimen have been observed across all cohorts. 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. The ENCORE 601 study also incorporates an extensive biomarker assessment of pre- and on-treatment blood and tumor samples from all patient cohorts with the goal of identifying a patient enrichment strategy that may predict enhanced clinical benefit across various cohorts and, therefore, potentially inform the design of future registration-directed studies.

"The additional data from the ENCORE 601 program continue to support the potential for the entinosta pembrolizumab combination to serve as an effective therapeutic option across a variety of indications," said Briggs Morrison, M.D., Chief Executive Officer of Syndax. "We are especially pleased to be able to share preliminary findings from our efforts to identify biomarkers that could aid in predicting which patients may derive a clinical benefit from this combination therapy. We have now identified a potential registration pathway in NSCLC and look forward to providing further updates as our plans come together."

NSCLC Update
The PD-(L)1 pretreated NSCLC cohort, which enrolled patients who have received prior chemotherapy and anti-PD-(L)1 treatment, provides the most mature dataset from the Company’s ongoing biomarker analyses. At the time of data cut-off, there were 6 confirmed partial responses (PRs) among the first 57 patients enrolled, for an 11% objective response rate (ORR) (95% CI: 4-21%) among patients treated with the entinostat-pembrolizumab
combination regimen. A total of 4 of the 6 responders were negative for PD-(L)1 expression at study entry. Among the 57 patients enrolled, 22 were refractory to prior PD-(L)1 therapy, and only 4 had a documented prior response to PD-(L)1 therapy. Median duration of prior PD- (L)1 therapy was < 6 months and the median time between last dose of prior PD-(L)1 therapy and first dose with the entinostat-pembrolizumab combination was 65 days. The median duration of response (DOR) to the entinostat-pembrolizumab combination was 4.6 months,
with the longest observed response over 14 months. At the time of the data cut-off, 7 patients remain on study.
Blood samples were collected and analyzed for 51 of the 57 NSCLC patients enrolled. By measuring pre-treatment baseline levels of classical peripheral blood monocytes (CD14+CD16-HLA-DRhi), the Company has been able to identify a subset of patients that appears to exhibit enhanced clinical benefit to the entinostat-pembrolizumab combination
regimen. Preliminary results from this assessment indicate that patients characterized by elevated baseline levels of monocytes ("high monocyte" subset, n=14) had a confirmed ORR of 29% (4 PRs/14 patients) and a Progression Free Survival (PFS) of 5.4 months, which compares favorably to the 2.8 month benefit recently demonstrated in NSCLC patients treated with third-line chemotherapy following progression after platinum doublet and PD-(L)1
treatment¹. In contrast, the subgroup of patients characterized by lower baseline levels of monocytes ("low monocyte" subset, n=37) had a confirmed ORR of 5% (2 PRs/37 patients) and a PFS of 2.5 months. The overall patient population (n=57) achieved a PFS of 2.7 months. Based upon these findings, the Company has identified a potential registration path in patients with NSCLC who have progressed on a PD(L)1 inhibitor. The trial is anticipated to commence by the end of 2018.

"Monocyte levels may reflect the ability of the immune system to respond after elimination of immune suppression," said Dmitry I. Gabrilovich, M.D., Ph.D., Christopher M. Davis Professor and Program Leader, Immunology, Microenvironment and Metastasis Program at The Wistar Institute. "The data from this PD-1 pre-treated population suggest that monocytes are associated with positive clinical outcome from entinostat combined with pembrolizumab, and if confirmed, can potentially be used for patient selection in future studies."

"NSCLC patients whose disease has progressed on PD-(L)1 and chemotherapy are in need of options that offer meaningful clinical benefits. Initial findings from this cohort of NSCLC patients receiving the entinostat-pembrolizumab combination provide encouraging benefit in ORR and PFS," said Leena Gandhi, M.D., Ph.D., Director of Thoracic Medicine Oncology Program at NYU Langone’s Perlmutter Cancer Center. "Although more data is needed, promising results for a population of patients with high monocyte counts further highlight that a selection strategy may
lead to enhanced benefits for patients."

Melanoma and MSS-CRC Update Within the anti-PD-1 pretreated melanoma cohort, a total of 6 confirmed PRs (ORR 18%; 95% CI: 6.8-34.5%) and 3 unconfirmed PRs were observed in the 34 evaluable patients at the time
of the data cut-off. Among these patients, 16 were PD-1 refractory, and only 2 had a documented response to prior anti-PD-1 therapy. The majority of these evaluable patients, 22 of 34, previously received the anti-CTLA-4 antibody YERVOY (ipilimumab) in addition to an anti-PD-1 regimen. Two of the 3 patients with unconfirmed responses had progressive disease within 6 weeks of the scan, while the third patient discontinued due to an adverse event. The median duration of prior anti-PD-1 therapy was < 6 months, and the median time between last dose of prior anti-PD-1 therapy and first dose with the entinostat-pembrolizumab combination was 64 days. The median DOR to the entinostat-pembrolizumab combination was 9.1 months. Four of the 34 patients remain on therapy as of the data cut-off date, while 3 of the 34 evaluable patients received therapy for over a year.

Enrollment in this cohort was recently completed (n=55), and further efficacy analyses and biomarker assessments from the recently enrolled patients will be utilized to supplement and strengthen the Company’s development strategy for melanoma.

Within the MSS-CRC cohort, 16 patients were initially enrolled, with a median of three lines of prior therapy in the advanced setting. One patient from the initial patient cohort had a confirmed PR and remains on treatment at >6 months. Nine patients experienced stable disease as best response, 2 for at least 4 months. As the Company recently announced, following discussions with investigators and collaborator Merck, the decision was made to expand enrollment of this cohort to include a total of 37 patients in the first stage of the Simon-two stage study. Enrollment is expected to resume into the modified stage 1 cohort by the end of the second quarter, with
at least three responses required to advance to the second stage, at which point an additional 47 patients would be enrolled. A decision on whether to continue to the second stage of this cohort is expected in the first half of 2019. As with the other ENCORE 601 cohorts, peripheral blood and pre- and on-treatment biopsies are being evaluated.

The data announced today will be presented in poster presentations at the upcoming ASCO (Free ASCO Whitepaper) meeting:

Title: Efficacy and safety of entinostat (ENT) and pembrolizumab (PEMBRO) in patients with nonsmall cell lung cancer (NSCLC) previously treated with anti-PD-(L)1 therapy
First Author: Leena Gandhi, MD, PhD, NYU Perlmutter Cancer Center
Abstract Number: 9036
Poster Session: Lung Cancer—Non-Small Cell Metastatic
Poster Board: 359
Date and Time: Sunday, June 3, 2018, 8:00-11:30 AM CT, Hall A

Title: Efficacy and safety of entinostat (ENT) and pembrolizumab (PEMBRO) in patients with melanoma progressing on or after a PD-1/L1 blocking antibody
First Author: Sanjiv S. Agarwala, MD, St. Luke’s Hospital
Abstract Number: 9530
Poster Session: Melanoma/Skin Cancers
Poster Board: 357
Date and Time: Monday, June 4, 2018, 1:15-4:45 PM CT, Hall A

Title: ENCORE 601: A phase 2 study of entinostat in combination with pembrolizumab in patients with microsatellite stable metastatic colorectal cancer
First Author: Nilofer Saba Azad, MD, Sidney Kimmel Cancer Center at Johns Hopkins University
Abstract Number: 3557
Poster Session: Gastrointestinal (Colorectal) Cancer
Poster Board: 50
Date and Time: Sunday, June 3, 2018, 8:00-11:30 AM CT, Hall A

Conference Call and Webcast
In connection with today’s announcement, Syndax’s management team will host a conference call and live audio webcast at 8:30 a.m. ET today, Thursday, May 17, 2018.

The live audio webcast and accompanying slides may be accessed through the Events & Presentations page in the Investors section of the Company’s website at www.syndax.com. Alternatively, the conference call may be accessed as follows:
Conference ID: 5778787
Domestic Dial-in Number: 1-855-251-6663
International Dial-in Number: 281-542-4259

Live webcast: View Source For those unable to participate in the conference call or webcast, a replay will be available for 30 days on the Investors section of the Company’s website, www.syndax.com.

On May 17, 2018 Cellerant Therapeutics, Inc., a clinical-stage company developing innovative immunotherapies for hematologic malignancies and other blood-related disorders, reported that investigators from Cellerant’s recently completed Phase 2 clinical trial of CLT-008 (romyelocel-L, human myeloid progenitor cells) will present key study results at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2018 Annual Meeting in Chicago, June 1-5, 2018, and at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Stockholm, June 14-17, 2018 (Press release, Cellerant Therapeutics, MAY 17, 2018, View Source [SID1234526782]).

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!

"AML patients who undergo induction chemotherapy suffer severe and prolonged neutropenia, and the results from this study show significantly reduced infections in the CLT-008 group relative to control"

Tweet this
Cellerant is developing CLT-008, a universal, off-the-shelf cell therapy intended to prevent infections during neutropenia. Neutropenia is a serious side effect of myelosuppressive chemotherapy that leaves patients at high risk of serious, potentially life-threatening infections, leading to prolonged hospitalization and often reduced or delayed treatment doses. The Company conducted a randomized, controlled Phase 2 study of CLT-008 in patients newly diagnosed with acute myeloid leukemia (AML) who received induction chemotherapy.

"AML patients who undergo induction chemotherapy suffer severe and prolonged neutropenia, and the results from this study show significantly reduced infections in the CLT-008 group relative to control," said Ram Mandalam, Ph.D., CEO of Cellerant Therapeutics. "This product addresses a serious unmet need in AML patients. We are excited to present the study results at these two important medical meetings, and look forward to advancing CLT-008 to a Phase 3 study."

Presentation details are as follows:

ASCO Abstract #7043: Abboud, et al., A randomized controlled open label exploratory trial of CLT-008 myeloid progenitor cells (MPC) to decrease infections during induction for AML. Poster discussion on June 4, 2018, 8:00-11:30am CDT. Presenting author: Farhad Ravandi, M.D., Janiece and Stephen A. Lasher Professor of Medicine, University of Texas MD Anderson Cancer Center.

EHA Abstract #1405: Desai, et al., Decreased incidence of infection, use of antibacterials and days in hospital after administration of CLT-008 myeloid progenitor cells to subjects receiving AML induction therapy: Phase 2 Study Results. Oral presentation on June 16, 2018, 4:45-5:00pm CEST. Presenting author: Pinkal Desai, M.D., M.P.H., Assistant Professor of Medicine, Weill Cornell Medicine, New York.

On May 17, 2018 Veru Inc. (NASDAQ: VERU), a urology and oncology biopharmaceutical company, reported the publication of data from preclinical studies of VERU-111, a novel oral alpha and beta tubulin inhibitor, showing potent activity in a highly resistant model of human prostate cancer (Press release, Veru, MAY 17, 2018, View Source [SID1234529113]). An abstract of the data was published as part of the upcoming 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago.

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!

Oral VERU-111 was evaluated in the 22Rv1 prostate cancer model, which represents a highly resistant and aggressive form of the disease possessing androgen receptor splice variants that are commonly found in prostate cancer resistant to hormonal approaches like abiraterone and enzalutamide. In the same model, docetaxel administered by injection did not have significant effect on tumor growth. Animals receiving docetaxel lost weight on the study, a surrogate for toxicity, whereas those on VERU-111 either maintained or gained weight while receiving the drug.

"The findings in this clinically relevant model of prostate cancer provide us with additional support and enthusiasm for evaluating VERU-111 in a Phase 1/2 clinical trial, which is scheduled to commence later this year. This is an animal model in which few drugs have been shown to be active. In addition, VERU 111 may be effective against other tumor types known to be sensitive to taxanes that are already FDA approved," said Mario Eisenberger, MD, the Dale Hughes Professor of Oncology at The Johns Hopkins University.

"Oral VERU-111 has shown positive and encouraging signs to become an important therapeutic option for a particularly challenging form of prostate cancer. We are studying VERU-111 in multiple other cancers, the data of which is also being published at ASCO (Free ASCO Whitepaper) this year. We have begun performing the required toxicity studies and our IND submission and first clinical studies are planned for later this year," said Mitchell Steiner, M.D., Chairman, President and Chief Executive Officer of Veru.

About VERU-111
VERU-111 is a novel oral therapy targeting alpha and beta tubulin for the treatment of metastatic prostate, breast, endometrial, ovarian, and other cancers. In 2017, there were approximately 161,000 new cases of prostate cancer in the U.S. and about 25% of these men will die from the disease. In the U.S., 5% of men with prostate cancer will have metastatic cancer and up to 30% of men with high-risk, localized prostate cancer will develop metastatic cancer following initial therapy. The median survival of patients with metastatic prostate cancer ranges from 3.2 to 4.5 years. For these men, the 1st line therapy is androgen deprivation therapy, or medical castration. Although most will initially respond, nearly all these patients will progress to metastatic castration resistant prostate and have a poor prognosis with an average survival of 1.5 years. New 2nd line hormonal agents, like XTANDI (enzalutamide) and ZYTIGA (abiraterone/prednisone) have resulted in an additional four to five months of average survival, but nearly all men on these agents will develop progressive metastatic prostate cancer.

Drugs like VERU-111 that target tubulin, the subunits of microtubules, have been shown to be the most effective targeted cytotoxic chemotherapy for the treatment of metastatic prostate cancer. Microtubules are critical for cancer cell replication to stimulate genes for cancer cell proliferation. Docetaxel and cabazitaxel are examples of FDA-approved chemotherapy drugs that are given intravenously (IV) that target tubulin to treat metastatic prostate cancer. Although effective, the challenges for this class of chemotherapy drugs, also known as taxanes, include that they must be given intravenously (IV) and that the cancer cells develop resistance to taxanes. There are also serious safety concerns with IV taxanes which include serious hypersensitivity reactions, myelosuppression and neurotoxicity such as peripheral neuropathy and muscle weakness.

Unlike taxanes which bind to just the beta subunit of tubulin, VERU-111 binds strongly to both the alpha and beta subunits of tubulin. VERU-111 has: high oral bioavailability; less resistance as it does not interact with multiple drug resistance proteins so it cannot be pumped out of the cancer cell; minimal drug to drug interactions and high activity against many tumor types including: prostate cancer resistant to drugs like enzalutamide, AR-V7 positive and taxanes, as well as triple negative breast cancer, ovarian cancer, pancreatic cancer, lung cancer, and melanoma. In preclinical studies, VERU-111 appears to have less toxicity and less suppression of white blood cells compared to taxanes and other chemotherapy agents.

Production of the VERU-111 active pharmaceutical ingredient and preclinical safety toxicology studies required for an IND are expected to be completed in 2018. We anticipate filing an IND in 2018 and Phase 1/2 studies are planned for late 2018. Phase 1 studies of VERU-111 are planned in men who have metastatic prostate cancer that has progressed while taking androgen deprivation therapy and abiraterone or enzalutamide as well as in patients with metastatic breast, endometrial, and ovarian cancers. In the U.S., there is a $5 billion annual market for 2nd line hormone therapies for prostate cancer and a $4.8 billion annual market for IV-given taxanes and vinca alkaloids chemotherapies (docetaxel $1 billion and cabazitaxel $500 million in prostate cancer) per Decision Resources Group and Allied Market Research. Second line hormonal therapies like enzalutamide and abiraterone/prednisone have almost complete cross-resistance and should not be used in sequence for the treatment of metastatic prostate cancer. VERU-111 could be substituted for IV given docetaxel and cabazitaxel antitubulin chemotherapies. VERU-111 could also be developed as an oral dosing alternative to chemotherapies for the treatment of metastatic breast, endometrial and ovarian cancers as these tumors that responded to IV taxane chemotherapies.

On May 17, 2018 Seattle Genetics, Inc. (Nasdaq: SGEN) reported the appointment of Roger D. Dansey, M.D., as Chief Medical Officer (Press release, Seattle Genetics, MAY 17, 2018, View Source;p=RssLanding&cat=news&id=2349629 [SID1234526766]). Dr. Dansey brings extensive experience in cancer drug development, most recently from Merck Inc. where he was Therapeutic Area Head for Late Stage Oncology, responsible for the ongoing registration efforts for KEYTRUDA (pembrolizumab) across multiple tumor types.

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!

"Roger’s appointment reflects the growing importance of late-stage clinical drug development at Seattle Genetics as we transition to a global, multi-product oncology company," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "Roger’s drug development and approval experience at industry leaders, including Merck, Gilead and Amgen, his deep oncology background and proven ability to collaborate and lead teams, make him an ideal fit for Seattle Genetics as we strive to bring transformative therapies to people with cancer."

Dr. Dansey stated, "This is an exciting time at Seattle Genetics with both a growing, approved drug in ADCETRIS as well as a product pipeline with important new opportunities, including three solid tumor programs in ongoing or planned pivotal trials. I look forward to working with the many talented individuals at Seattle Genetics to bring these new therapies to patients."

Roger D. Dansey was Senior Vice President at Merck Inc. from January 2015 to April 2018, where he led the company’s late-stage oncology development efforts including the approved PD-1 inhibitor, KEYTRUDA. Prior to joining Merck, Dr. Dansey was Vice President, Oncology Clinical Research at Gilead Sciences. He initially joined the industry at Amgen working in roles of increasing responsibility in Amgen’s oncology and hematology therapeutic area, including as Global Development Leader for XGEVA. He received his Medical Degrees from the University of Witwatersrand, Johannesburg, South Africa.

Dr. Dansey succeeds Jonathan Drachman, M.D., who will remain with Seattle Genetics as a strategic advisor for innovation. Dr. Siegall added, "Jonathan has been a key contributor and leader at Seattle Genetics since joining the company nearly 14 years ago. He has been instrumental in the development of ADCETRIS, the expansion of Research and Development and advancement of our robust pipeline of both antibody-drug conjugates and novel immuno-oncology programs. I look forward to working with Jonathan on innovation initiatives that can ultimately benefit cancer patients."