On September 17, 2018 G1 Therapeutics, Inc. (Nasdaq: GTHX), a clinical-stage oncology company, reported that it is expediting analyses of myelopreservation data from its randomized Phase 2 trial of trilaciclib in combination with chemotherapy and Tecentriq (atezolizumab) in first-line small cell lung cancer (SCLC) (Press release, G1 Therapeutics, SEP 17, 2018, View Source [SID1234529790]). Myelopreservation results from the trial will be reported in the fourth quarter of 2018.

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"We elected to make myelopreservation the primary outcome of the randomized trilaciclib/chemotherapy/Tecentriq trial based on the strength of the first-line small cell lung cancer myelopreservation results from our randomized Phase 2 trilaciclib/chemotherapy trial, which we reported in March," said Raj Malik, M.D., Chief Medical Officer and Senior Vice President, Research and Development. "This protocol amendment, which we have discussed with U.S. and European regulatory authorities, enables us to accelerate analyses of mature myelopreservation data collected from the trilaciclib/chemotherapy/Tecentriq trial. The trial will remain blinded to investigators and participants, with no impact on our timeline to report overall survival data."

This randomized, double-blind Phase 2 trial enrolled 107 patients to receive trilaciclib or placebo in combination with chemotherapy (carboplatin + etoposide) and Tecentriq as first-line treatment for SCLC. The trial is evaluating the myelopreservation potential of trilaciclib. Myelopreservation is the ability to preserve hematopoietic stem and progenitor cell function, as well as immune system function, during chemotherapy. Anti-tumor efficacy measures including overall response rate, progression-free survival and overall survival are also being evaluated. Under the revised protocol, myelopreservation results are now the primary outcome and overall survival is being assessed as a secondary outcome. The trial completed enrollment in February 2018.

"Data from the trilaciclib/chemotherapy/Tecentriq trial have the potential to confirm the myelopreservation results observed in our randomized Phase 2 trial of trilaciclib in combination with chemotherapy. Both trials evaluated trilaciclib in first-line small cell lung cancer using the same chemotherapy backbone," said Mark Velleca, M.D., Ph.D., Chief Executive Officer. "By the end of the year we will have myelopreservation data from all four randomized Phase 2 trials of trilaciclib, including three in small cell lung cancer and one in triple negative breast cancer. In these trials, trilaciclib was used in first-, second- and third-line settings in combination with a variety of chemotherapy regimens. We plan to discuss the totality of the data, which includes approximately three hundred participants who received trilaciclib, with U.S. and European regulatory authorities in the first half of 2019."

Webcast and Conference Call

The G1 management team will host a webcast and conference call at 8:30 a.m. ET today to discuss the trilaciclib clinical development program. The live call may be accessed by dialing 866-763-6020

About Trilaciclib

Trilaciclib is a first-in-class myelopreservation therapy designed to preserve hematopoietic stem and progenitor cell function, as well as immune system function, during chemotherapy. Trilaciclib is a short-acting intravenous CDK4/6 inhibitor administered prior to chemotherapy and has the potential to significantly improve treatment outcomes.

Trilaciclib is being evaluated in four randomized Phase 2 clinical trials. In March 2018, G1 announced positive Phase 2 data showing myelopreservation benefits in newly diagnosed, treatment-naive small cell lung cancer (SCLC) patients (NCT02499770). Additional results from this trial will be reported at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress being held October 19-23. The company plans to report data from three other randomized Phase 2 trials in 2018: a trial in combination with chemotherapy and Tecentriq in first-line SCLC, (NCT03041311), a trial in combination with chemotherapy in previously treated SCLC (NCT02514447), and a trial in combination with chemotherapy in triple-negative breast cancer (NCT02978716).

On September 17, 2018 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported that it has entered into a collaboration with ONO Pharmaceutical Co., Ltd. for the joint development and commercialization of two off-the-shelf CAR-T cell product candidates (Press release, Fate Therapeutics, SEP 17, 2018, View Source [SID1234529463]). Using Fate Therapeutics’ proprietary induced pluripotent stem cell (iPSC) product platform, the two CAR T-cell collaboration candidates will each be derived from a clonal master iPSC line engineered to completely eliminate endogenous TCR expression, insert a chimeric antigen receptor (CAR) into the TRAC locus and incorporate other anti-tumor functionality. This transformative approach enables the cost-effective production of cell-based cancer immunotherapies that are uniformly engineered, extensively characterized and homogeneous in composition, and can be consistently and repeatedly mass produced and delivered to patients in an off-the-shelf manner.

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"We are delighted to collaborate with ONO, a global leader in oncology with a long history of developing innovative breakthrough cancer drugs," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "This partnership with ONO enables Fate to further enhance its expertise in targeting solid tumors and to accelerate the global development of our pipeline of off-the-shelf, iPSC-derived CAR-T cell product candidates."

Under the terms of the strategic option agreement, Fate Therapeutics and ONO will jointly advance each iPSC-derived CAR-T cell collaboration candidate to a pre-defined preclinical milestone. The first iPSC-derived CAR T-cell candidate targets an antigen expressed on certain lymphoblastic leukemias, and Fate Therapeutics retains global responsibility for development and commercialization with ONO having an option to assume responsibilities in Asia. The second candidate targets a novel antigen identified by ONO expressed on certain solid tumors, with ONO having an option to assume global responsibility for further development and commercialization and Fate Therapeutics retaining the right to co-develop and co-commercialize the candidate in the United States and Europe. For both collaboration candidates, Fate Therapeutics retains manufacturing responsibilities on a global basis.

"ONO identified Fate Therapeutics as the partner of choice for the generation of off-the-shelf CAR T-cell cancer immunotherapies in our portfolio," said Hiromu Habashita, Corporate Officer, and Executive Director of Discovery & Research of ONO. "We are excited to work with Fate Therapeutics and apply its industry-leading iPSC product platform to develop and deliver the next-generation of CAR T-cell therapies for cancer patients."

Fate Therapeutics will receive an upfront payment and committed research funding during the preclinical option period, and is eligible to receive a preclinical option exercise fee, clinical, regulatory and commercialization milestone payments and tiered royalties on net sales by ONO in connection with the development and commercialization of each collaboration product by ONO in the ONO territory

On September 17, 2018 Unum Therapeutics Inc. (NASDAQ: UMRX), a clinical-stage biopharmaceutical company focused on the development of cellular immunotherapies based on its novel, universal Antibody-Coupled T cell Receptor (ACTR) technology platform, reported that the Company will be presenting data on the first dose level (40×106 ACTR+ T cells) of its ATTCK-20-03 clinical trial evaluating ACTR707 in combination with rituximab in patients with relapsed or refractory CD20-positive B cell non-Hodgkin Lymphoma (r/r NHL) (Press release, Unum Therapeutics, SEP 17, 2018, View Sourcenews-releases/news-release-details/unum-therapeutics-announces-abstract-accepted-presentation" target="_blank" title="View Sourcenews-releases/news-release-details/unum-therapeutics-announces-abstract-accepted-presentation" rel="nofollow">View Source [SID1234529485]). Three of the six patients treated at the first dose level achieved a complete response, two of which remained ongoing at the time of the most recent data cut off. No dose-limiting toxicities (DLTs) were observed in any of the four DLT-evaluable patients, and no serious or severe adverse events of cytokine release syndrome or neurotoxicity were observed in any patients. These data will be presented at the Fourth Annual CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) on September 30 in New York, New York.

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"These preliminary clinical data suggest that complete responses may be achieved without cytokine release syndrome, further validating the potential of our proprietary ACTR technology platform," said Chuck Wilson, Chief Executive Officer of Unum. "The ATTCK-20-03 trial is a key element of our strategy to develop novel therapeutics for patients with no available treatment options."

"Complete responses observed in this heavily pre-treated patient population at the first dose level of the ATTCK-20-03 trial support the potential potency of ACTR T cells for these patients," said Michael Vasconcelles, Chief Medical Officer of Unum. "Based upon this encouraging preliminary profile, we look forward to continuing the dose escalation phase of this study. We expect these and future data to support selection of an ACTR product candidate to progress into potential registration trials in patients with r/r NHL."

Enrollment and ACTR707 dosing in the second dose cohort (60×106 ACTR+ T cells) of the ATTCK-20-03 trial has been completed and dose escalation is proceeding. The Company expects to present additional data from this study later this year.

Safety and Preliminary Efficacy of ACTR707, Autologous T Lymphocytes Expressing an Antibody-Coupled T Cell Receptor, in Combination with Rituximab in Subjects with Relapsed or Refractory CD20-Positive B-cell Lymphoma (Abstract #A003)

Presenter: Dr. Veronika Bachanova, University of Minnesota

Date: Sunday, September 30, 2018, 11:45am – 2:15pm

Location: New York Marriott Marquis, Westside Ballroom

ATTCK-20-03 is a Phase I, multi-center, open label, single arm clinical trial evaluating ACTR707 in combination with rituximab in patients with r/r NHL. Eligible patients for enrollment must have, among other criteria, received adequate prior anti-lymphoma therapy, including rituximab and chemotherapy, for their CD20-positive r/r NHL. Key eligibility criteria include: pre-specified eligible NHL subtypes, including DLBCL, disease progression following immediate prior therapy, adequate organ function and performance status, and measurable disease. The trial design includes a dose escalation phase using an adaptive design, followed by a cohort expansion phase. Primary study objectives are to characterize the safety of ACTR707 in combination with rituximab and to determine the maximum tolerated dose and proposed recommended Phase 2 dose. Secondary study objectives include: assessment of the anti-lymphoma activity of the combination, ACTR707 persistence, rituximab pharmacokinetics, and inflammatory markers and cytokine levels. Following leukapheresis, each patient receives lymphodepletion followed by the first infusion of rituximab and then a single infusion of ACTR707. Rituximab infusions continue on a regular, pre-specified schedule.

Data in the first cohort of the trial demonstrate complete responses at the first response assessment in 3/6 patients treated with ACTR707 in combination with rituximab, two of which remained ongoing at the time of the most recent data cut off. There were no serious or severe adverse events of cytokine release syndrome, neurotoxicity, or autoimmune events. Grade 3 or higher adverse events were mostly hematologic including neutropenia (n=2), febrile neutropenia (n=2), and thrombocytopenia (n=1). ACTR+ T cells were detectable in all subjects and ACTR+ T cells persisted in the presence of continued rituximab administration. These results support the continued dose escalation of ACTR707 in combination with rituximab.

Conference Call and Webcast
Unum will host a conference call and webcast at 8:30 a.m. EDT today to discuss the data. To participate in the conference call, please dial (866) 300-3411 (domestic) or (636) 812-6658 (international) and enter the conference code: 2958105. To join the live webcast, please visit the investor relations section of the Unum Therapeutics website at View Source at least 10 minutes before the event begins. A webcast replay will be available at the same location on the Unum Therapeutics website beginning approximately two hours after the event and will be archived for 90 days.

About ACTR707

ACTR707 is an investigational drug that may represent an important construct not only for adult patients with CD20+ r/r NHL, when used in combination with rituximab, but also for patients with other cancer types when used in combination with other antibodies. ACTR707 was identified through a comprehensive high-throughput screening effort aimed at identifying receptors with improved functional characteristics across several dimensions. In preclinical testing, ACTR707 demonstrated potent activity against a wide range of hematologic and solid tumor cancers. Given the challenges of the immunosuppressive solid tumor microenvironment, Unum believes that ACTR707’s increased activity may be particularly important in addressing solid tumor cancers. ACTR707 is currently being tested in combination with rituximab in patients with r/r NHL in a Phase I multi-center open label clinical trial, ATTCK-20-03. Testing is expected to be initiated later in 2018 in ATTCK-34-01, a Phase I multi-center open label clinical trial exploring the combination of ACTR707 with trastuzumab in patients with HER2+ advanced cancers.

On September 17, 2018 Cytori Therapeutics (NASDAQ: CYTX) ("Cytori" or the "Company") reported that it received FDA orphan drug designation for its ATI-1123 chemotherapy drug product candidate, an albumin-stabilized pegylated liposomal docetaxel, for the treatment of small cell lung cancer (Press release, Cytori Therapeutics, SEP 17, 2018, View Source [SID1234529464]).

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The FDA’s Orphan Drug Designation Program provides orphan status to drugs, such as ATI-1123, which are intended for the safe and effective treatment of rare diseases/disorders that affect fewer than 200,000 people in the U.S. Sponsors of a drug receiving orphan designation qualify for various incentives including tax credits for clinical testing, 7 years of marketing exclusivity following FDA approval, and a waiver of prescription drug user fees.

Small cell lung cancer (SCLC), which accounts for approximately 15% of bronchogenic carcinomas with 33,375 new cases and 23,380 deaths estimated for 2017, has been identified by Cytori as a compelling target for ATI-1123. While SCLC is responsive to chemotherapy and radiation therapy, cure occurs only in ~20% of patients, generally restricted to those with limited stage disease. The remaining 80% of patients, including all patients with extensive disease, relapse within months of completing their initial therapy. Availability of 2nd line therapy options are limited, toxic, and provide little benefit in terms of extending survival. Topotecan is the only FDA-approved agent for 2nd line treatment of SCLC and is associated with an overall response rate of 24%, median response duration or time to progression of 14 weeks, and median overall survival of 25 weeks. Treatment usually involves a consecutive 5 day regimen of either IV or oral administration of drug, both which have black box warnings for severe myelosuppression as their use is associated with substantial morbidity including bone marrow suppression leading to neutropenia, thrombocytopenia and anemia requiring interventions of transfusion and growth factor support.

No major treatment advances for SCLC have occurred over the past 30 years. Hence, there remains a significant unmet need for novel agents with better safety profiles both for patients who cannot tolerate the adverse effects of 1st line chemo-radiotherapy and for relapsed/refractory patients who receive Topotecan. Cytori’s ATI-1123 has been designed to fill this need. ATI-1123’s combination of improved liposome stability, reduced toxicity, and superior delivery are expected to provide a therapeutic for SCLC that offers comparable or better efficacy to currently-available standards while having a less intensive administration routine and improved side effect profile.

Cytori is also exploring the development of ATI-1123 to address the shortcomings of docetaxel, a workhorse chemotherapy drug which generated $2.7B in worldwide sales at its peak. Compared to docetaxel, ATI-1123 may have potential to improve safety by removing the need for unwanted solvents, reduce morbidity by eliminating the requirement for standard pretreatment medications, provide better patient convenience and comfort via less time spent in the treatment center, decrease the cost of therapy, and enhance systemic docetaxel exposure.

A U.S. Phase 1 clinical study of ATI-1123 has been completed and published. Of the 29 patients in the study with cervical, gastric, melanoma, non-small cell lung, ovarian, pancreatic, prostate, thyroid, urachal and uterine cancers, 82% demonstrated a clinical benefit with ATI-1123. ATI-1123 exhibited an improved safety profile versus the Taxotere label with a 31% reduction in neutropenia and anemia. Further, ATI-1123 showed a 20% increase in maximum tolerated dose versus standard docetaxel and signs of efficacy with 1 partial responder.

On September 16, 2018 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported four oral clinical data presentations on two of its late-stage investigational therapies, tislelizumab and zanubrutinib, at the 21st Annual Meeting of the Chinese Society of Clinical Oncology (CSCO) (Press release, BeiGene, SEP 16, 2018, View Source [SID1234529451]). The meeting will take place September 19 – 23 in Xiamen, China. Tislelizumab is an investigational anti-PD-1 antibody, and zanubrutinib is an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK).

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Oral Presentations:

Title: Clinical Profile of Tislelizumab in Chinese Patients with Microsatellite Instability High (MSI-H) or Mismatch Repair-Deficient (MMRd) Solid Tumors: Preliminary Results from an Indication-Expansion Cohort
Abstract ID: 449
Location: Second Floor, Straits Hall
Date: Thursday, September 20, 2018
Time: 16:45 – 16:55 (CST)
Presenter: Lin Shen, M.D.


Title: Tislelizumab Combined with Chemotherapy as First-Line Treatment in Chinese Patients (Pts) with Advanced Lung Cancer
Abstract ID: 450
Location: First Floor, Concert Hall
Date: Friday, September 21, 2018
Time: 11:30 – 11:38 (CST)
Presenter: Jie Wang, M.D., Ph.D.


Title: Preliminary Results with Tislelizumab in Chinese Patients with Non-Small Cell Lung Cancer (NSCLC)
Abstract ID: 448
Location: First Floor, Concert Hall
Date: Friday, September 21, 2018
Time: 11:38 – 11:45 (CST)
Presenter: Qing Zhou, M.D.


Title: A Phase 1 Clinical Study to Investigate the Safety, Tolerability and Pharmacokinetics/Pharmacodynamics of BTK Inhibitor BGB-3111 in Chinese Patients with B-Cell Lymphoma
Abstract ID: N/A
Location: First Floor, G Hall
Date: Saturday, September 22, 2018
Time: 08:30 – 08:45 (CST)
Presenter: Jun Zhu, M.D.

About Tislelizumab
Tislelizumab (BGB-A317) is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. Discovered by BeiGene scientists in Beijing, tislelizumab is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. Tislelizumab has demonstrated high affinity and specificity for PD-1. It is potentially differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells, based on preclinical data. Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumor cancers outside of Asia (except Japan). Tislelizumab’s new drug submission for the treatment of patients with relapsed/refractory classical Hodgkin’s lymphoma (R/R cHL) has been accepted and is under review by the National Medical Products Administration of China (NMPA, formerly known as CFDA or CDA).

About Zanubrutinib
Zanubrutinib (BGB-3111) is an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK) that was discovered in BeiGene’s research facilities in Beijing, China. It is currently being evaluated in a broad pivotal clinical program globally and in China as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Zanubrutinib is under review as a Category 1 new drug submission for the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL) by the NMPA of China.