On December 11, 2017 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported the presentation of preclinical data from research led by The University of Texas MD Anderson Cancer Center demonstrating that CG’806, a highly potent pan-FLT3/pan-BTK inhibitor, exerts a profound anti-leukemia effect in human and murine leukemia cell lines harboring FLT-3 ITD mutations, mutations that are usually associated with very poor prognoses in leukemia patients. In addition, CG’806 demonstrates apoptosis, or programmed cell death, in AML patient samples by several mechanisms and is able to overcome resistance that is seen with other FLT3 inhibitors (Press release, Aptose Biosciences, DEC 11, 2017, View Source [SID1234522545]). The data were highlighted in poster presentations on Sunday and Monday, December 10 and 11, 2017 at the American Society of Hematology (ASH) (Free ASH Whitepaper) 59th Annual Meeting & Exposition, being held December 9-12 in Atlanta, GA.

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The poster The Pan-FLT3/BTK Multi-Kinase Inhibitor CG’806 Induces AML Killing in FLT-Mutant and Wild Type Cells, and Exerts Synergistic Pro-Apoptotic Effects with Concomitant Targeting of Anti-Apoptotic Bcl-2 and/or Mcl-1 demonstrated pronounced anti-leukemia activity of CG’806 against a broad array of AML cells, including those with FLT3-wild type, FLT3 with single mutations, or with FLT3 harboring dual ITD plus D835 or ITD plus F691 mutations, and it demonstrated synergistic effects in combination with Bcl-2 or Mcl-1 inhibitors even in FLT3 mutated AML cells. CG’806 elicited its broad spectrum killing of AML cells through its ability to suppress the FLT3 pathway as well the BTK, AURK, AKT and ERK signaling pathways that are differentially operative in different AML cells. Notably, CG’806 maintained cytotoxic activity against AML cells in the presence of FLT3 ligand and bone marrow stromal cells, and CG’806 demonstrated dose-dependent in vivo antitumor activity in a circulating AML murine model.

The poster CG’806, a Novel Pan-FLT3/BTK Multi-Kinase Inhibitor, Induces Cell Cycle Arrest, Apoptosis or Autophagy in AML Cells Depending on FLT3 Mutation Status further elucidated the anti-leukemia effect of CG’806. CG’806 exerted profound suppression of cell proliferation through G1 cell cycle arrest and induction of apoptosis in FLT3-mutant AML cells, which is associated with inhibition of mutant FLT3 signaling and the downstream p-AKT/p-mTOR/cyclin D1/p-Rb signaling axis. In contrast, CG’806 exerted a G2/M arrest in FLT3-wildtype (WT) cells through inhibition of aurora (AURK) and BTK kinases and induction of non-apoptotic cell death (autophagy or polyploidy). CG’806 sensitized AML cells to standard chemotherapeutic agents cytarabine and idarubicin and significantly enhanced pro-apoptotic effects. Taken together, these data support the development of CG’806 for a diverse set of AML patients with FLT3-ITD, FLT3-ITD plus additional TKD/gatekeeper mutations, as well as FLT3-WT.

Data were presented by members of the research team led by Michael Andreeff, M.D., Ph.D., Professor of Medicine, Haas Chair in Genetics, Department of Leukemia, at The University of Texas MD Anderson Cancer Center.

The poster presentations can be accessed on the Events & Presentations section of the Aptose website at the following link.

"As our mechanistic understanding of CG’806 grows, we are beginning to construct a framework of how a single molecule can inhibit specific clusters of kinases and kill a heterogeneous group of AML cells without observed toxicity to normal cells," commented William G. Rice, Ph.D., Chairman and Chief Executive Officer of Aptose. "As a pan-FLT3/pan-BTK multi-kinase inhibitor, CG’806 has the ability to kill a broad range of AML cells through inhibition of multiple oncogenic pathways that are differentially expressed in subgroups of cells. It appears to overcome the limitations of competitive FLT3 inhibitory agents, to enhance the AML cell killing effects of certain other chemotherapies, and to exhibit a robust therapeutic index. We look forward to initiating clinical trials of CG’806 in 2018."

Separately, Aptose and Oregon Health & Science University Knight Cancer Center researchers also announced new data on CG’806 presented at ASH (Free ASH Whitepaper) (see press release here).

In addition to the abstracts that were presented at ASH (Free ASH Whitepaper), two additional abstracts on CG’806 and two abstracts on APTO-253, Aptose’s small molecule c-Myc Inhibitor, have been published on the ASH (Free ASH Whitepaper) abstracts site. All abstracts will become part of the permanent ASH (Free ASH Whitepaper) and Blood abstracts archive.

About CG’806

CG‘806 is an oral, first-in-class pan-FLT3/pan-BTK inhibitor. This small molecule demonstrates potent inhibition of all wild type and mutant forms of FLT3 tested (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven 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 kinases operative in B cell malignancies, suggesting CG’806 may be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.

On December 11, 2017 MacroGenics, Inc. (NASDAQ:MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as autoimmune disorders and infectious diseases, reported the presentation of clinical data from its ongoing Phase 1 study of flotetuzumab in an oral session at the 59th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Atlanta, Georgia (Press release, MacroGenics, DEC 11, 2017, View Source [SID1234522556]). John E. Godwin, M.D., Program Leader, Hematologic Malignancies at Earle A. Chiles Research Institute at Providence Cancer Center in Portland, Oregon presented "Preliminary Results of a Phase 1 Study of Flotetuzumab, a CD123 x CD3 Bispecific DART Protein, in Patients with Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome."

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The ongoing Phase 1, first-in-human study of flotetuzumab was designed to determine safety, tolerability, maximum tolerated dose and initial anti-leukemic activity in patients with relapsed or refractory acute myeloid leukemia (AML) or intermediate-2/high risk myelodysplastic syndrome (MDS). To date, a total of 57 patients have been enrolled, including 11 AML patients in the dose expansion cohort.

Consistent with the dose escalation data that was previously presented at ESMO (Free ESMO Whitepaper) Congress 2017 in September, flotetuzumab has continued to demonstrate acceptable tolerability in patients treated to date in the dose expansion cohort. Infusion-related reaction and cytokine release syndrome (CRS) were the most common adverse events observed, with Grade 3 CRS occurring in 9 of 57 patients (15.8%). Implementation of a two-step, lead-in dose as well as early intervention with anti-cytokine therapy has helped to limit the severity and incidence of CRS.

As of the data cut-off date, of the eight evaluable patients in the dose expansion cohort who received a lead-in dose followed by 500 ng/kg/day of flotetuzumab via continuous IV infusion, six patients (75%) have evidence of anti-leukemic activity, with three of these patients experiencing an objective response. This included two patients who experienced CR/CRi and one patient who achieved MLF (morphologic leukemia-free state).

The duration of response for the eight patients who have achieved a MLF, CRi or CR in the dose escalation and dose expansion cohorts ranged from 1.0 to 5.8 months, with five of these responses still ongoing as of the November 30, 2017 data cut-off.

Further, in a translational data poster presentation, MacroGenics also described studies that support a rationale for using checkpoint blockade as an approach to potentially enhance the anti-leukemic activity of flotetuzumab. Among these findings, modulation of the PD-1/PD-L1 pathway was observed in patients treated with flotetuzumab, and the combination of flotetuzumab and PD-1/PD-L1 inhibitors was shown to synergistically enhance T-cell mediated cytotoxicity against AML cell lines in vitro.

"We continue to be encouraged by the tolerability and anti-leukemic activity of flotetuzumab as well as by the early data regarding the durability of responses observed in patients from our ongoing Phase 1 study of flotetuzumab," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "In addition, given the data-supported rationale for combining flotetuzumab with anti-PD-1, we intend to initiate a combination study with the anti-PD-1 mAb, MGA012, in the coming months, while we continue to enroll the AML and MDS dose expansion cohorts. We look forward to sharing additional flotetuzumab clinical data in 2018."

The presentation at the 59th Annual ASH (Free ASH Whitepaper) meeting is available for download from the Events & Presentations page on MacroGenics’ website at View Source

About Flotetuzumab

Flotetuzumab (also known as MGD006 and S80880) is a clinical-stage molecule that recognizes both CD123 and CD3. CD123, the Interleukin-3 receptor alpha chain, has been reported to be over-expressed on cancer cells in a wide range of hematological malignancies, including AML and MDS. The primary mechanism of action of flotetuzumab is believed to be its ability to redirect T lymphocytes to kill CD123-expressing cells. To achieve this, the DART molecule combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123 on the target cancer cells.

Flotetuzumab is currently being evaluated at 13 clinical sites in the U.S. and Europe in a Phase 1 study designed to assess the safety, tolerability, maximum tolerated dose and initial anti-leukemic activity of the molecule in patients with relapsed/refractory AML or intermediate-2/high risk MDS. MacroGenics retains full development and commercialization rights to flotetuzumab in the U.S., Canada, Mexico, Japan, South Korea and India. Servier participates in the development of flotetuzumab and has exclusive rights to this molecule in all other countries. The U.S. Food and Drug Administration has granted orphan drug designation to flotetuzumab for the treatment of AML.

On December 11, 2017 RXi Pharmaceuticals Corporation (NASDAQ: RXII) reported that it has entered into a research collaboration with Medigene AG (MDG1, Frankfurt, Prime Standard, TecDAX) to explore potential synergies of using RXi’s self-delivering RNAi technology (sd-rxRNA) in combination with Medigene’s recombinant TCRs to develop modified T cells with enhanced efficacy and/or safety (Press release, RXi Pharmaceuticals, DEC 11, 2017, View Source [SID1234522533]). The preclinical research program will examine the applicability of RXi’s sd-rxRNA technology to be integrated into Medigene’s process to produce receptor-modified T cells with the ultimate goal to further improve Medigene’s T cell therapies for the treatment of cancer patients.

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Research teams at Medigene will closely work together with the scientists at RXi to explore potential advantages of transient down regulation of certain genes ("knock down") to prevent negative regulation of T cells expressing a recombinant TCR directed against a predefined tumor antigen. The two complementing technologies could lead to synergistic effects that might further sharpen and improve the therapeutic effects of Medigene’s receptor-modified T cells.

Markus Dangl, Senior Vice President Research and Preclinical Development of Medigene AG, comments: "We are very happy that we found a partner that is fully aligned with our vision to further improve our adoptive T cell therapy approach. We are convinced that this technology can help us to develop the next generation of recombinant T cells that are highly efficacious, also in challenging solid tumor environments. These T cells will contain features that have the potential to further enhance the efficacy and safety of our approach to bring highly beneficial cellular therapies to the market."

Dr. Geert Cauwenbergh, President and CEO of RXi Pharmaceuticals, adds: "We are excited to start this new collaboration. Medigene’s adoptive cell therapy, using their TCR platform, is a very attractive and promising development in immuno-oncology; and we are pleased with their decision to use our sd-rxRNA technology in combination with their TCR approach. The use of our immuno-oncology sd-rxRNA compounds with their receptor-modified T cells could potentially create a next generation of very powerful adoptive cell therapies against serious cancers that currently are difficult to target."

About Medigene’s TCR technology: The TCR technology aims at arming the patient’s own T cells with tumor-specific T-cell receptors. The receptor-modified T cells are then able to detect and efficiently kill tumor cells. This immunotherapy approach attempts to overcome the patient’s tolerance towards cancer cells and tumor-induced immunosuppression by activating and modifying the patient’s T cells outside the body (ex vivo).

TCR therapy is developed to utilize a higher number of potential tumor antigens than other T cell-based immunotherapies, such as chimeric antigen receptor T cell (CAR T) therapy. Medigene is preparing the clinical development of its first TCR candidates and is establishing a pipeline of recombinant T-cell receptors, and has established Good Manufacturing Practice (GMP)-compliant processes for their combination with patient-derived T cells.

Medigene AG (FSE: MDG1, ISIN DE000A1X3W00, Prime Standard, TecDAX) is a publicly listed biotechnology company headquartered in Martinsried near Munich, Germany. The company is developing highly innovative immunotherapies to target various forms and stages of cancer. Medigene concentrates on the development of personalized T cell-based therapies, with associated projects currently in pre-clinical and clinical development.

For more information, please visit View Source

On December 11, 2017 Celgene Corporation (NASDAQ: CELG) and bluebird bio, Inc. (Nasdaq: BLUE) reported that updated results from the ongoing CRB-401 Phase 1 clinical study of bb2121, an investigational anti-B-cell maturation antigen (BCMA) CAR T cell therapy, in 21 patients with late-stage relapsed/refractory multiple myeloma will be presented in an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, Georgia (Press release, bluebird bio, DEC 11, 2017, View Source [SID1234522486]).

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The objective of this Phase 1 dose-escalation study is to evaluate safety and efficacy of bb2121 and determine a recommended Phase 2 dose.

"Celgene has a longstanding commitment to patients with multiple myeloma through our extensive research efforts in this deadly blood cancer," said Nadim Ahmed, President, Hematology and Oncology for Celgene. "Looking ahead, we see BCMA as an important target in this disease and we believe bb2121 has the potential to create significant impact on the treatment approach and outcomes for these patients."

"The growing body of bb2121 clinical data are building a compelling story, further supporting the importance of the therapy’s unique features," said Dave Davidson, M.D., chief medical officer, bluebird bio. "The responses achieved in this relapsed and refractory patient population, combined with the generally tolerable safety profile, reinforce the potential role of bb2121 as a groundbreaking CAR T therapy in multiple myeloma."

Durable clinical responses in heavily pretreated patients with relapsed/refractory multiple myeloma: Updated results from a multicenter study of bb2121 anti-BCMA CAR T cell therapy (Abstract #740)

Presenter: James Kochenderfer, M.D., the Center for Cancer Research at the National Cancer Institute in Bethesda, Maryland

Date: Monday, December 11, 3:00 pm (Oral presentation)
Location: Hall C1 (Georgia World Congress Center)

Session Title: Myeloma: Therapy, excluding Transplantation I

The open-label Phase 1 CRB-401 study (NCT02658929) is evaluating the preliminary safety and efficacy of bb2121 anti-BCMA CAR T cell in patients with relapsed and/or refractory multiple myeloma. The study also evaluated the recommended dose of bb2121 for future studies.

Patients on study were heavily pre-treated, with a median of 7 prior therapies (range: 3 – 14):

100% previously treated with lenalidomide and bortezomib
91% previously treated with pomalidomide and carfilzomib
71% previously treated with daratumumab
29% of patients were penta-refractory (bortezomib, lenalidomide, carfilzomib, pomalidomide, daratumumab)
All patients had at least one prior autologous stem cell transplant (ASCT).
As of the October 2, 2017 data cut-off, 21 patients had been enrolled and dosed in the dose-escalation phase of the study, in four dose cohorts: 50 x 106, 150 x 106, 450 x 106 and 800 x 106 CAR+ T cells. This multi-center study has enrolled patients at nine sites in the U.S with central manufacturing performed at Celgene.
Patients received a conditioning regimen of cyclophosphamide and fludarabine, followed by an infusion of bb2121 anti-BCMA CAR T cells. The CAR T cells were produced from each patient’s own blood cells, which were modified using a proprietary lentiviral vector encoding the anti-BCMA CAR.

Results in the active dose cohorts (150 x 106, 450 x 106 and 800 x 106 CAR+ T cells; N=18) were:

Median follow-up was 40 weeks (range: 6.6-69)
17/18 (94%) patients achieved an objective response
16/18 (89%) patients achieved at least a very good partial response (VGPR)
10/18 (56%) patients achieved a complete response (CR, N = 7), or unconfirmed complete response (N = 3)
9 of 10 patients who were evaluable for MRD status were found to be MRD-negative
Median PFS has not been reached in the active dose cohorts. The PFS at 6 months and 9 months was 81% and 71%, respectively.
Three patients in the dose-escalation who responded to therapy subsequently experienced disease progression.
In the dose-escalation phase, 15/21 (71%) of patients had cytokine release syndrome (CRS), mostly Grade 1 & 2, with 2 patients experiencing Grade 3 CRS (9%). Four patients received tocilizumab, 1 (Grade 2 CRS) received steroids and in each case the CRS resolved within 24 hours. The most common treatment-emergent Grade 3-4 AEs in 21 infused patients were cytopenias commonly associated with lymphodepleting chemotherapy including neutropenia (86%), anemia (57%) and thrombocytopenia (43%). There were two deaths in the active cohorts at 22 and 69 weeks following infusion, respectively. The first was due to cardiac arrest and the second was due to myelodysplastic syndrome; both subjects were in a myeloma CR at their last study assessment prior to death. Based on the findings during dose escalation, a dose expansion phase of 12 subjects has started testing doses between 150-450 x 106 CAR+ T cells. In the dose expansion phase, one patient treated at the 450 x 106 CAR+ T cells dose experienced Grade 4 neurotoxicity including focal cerebral edema and subarachnoid hemorrhage. This patient had a high tumor burden, and a history of subarachnoid hemorrhage. The event was successfully managed, and the patient remains in the response group. No other Grade 3/4 neurotoxicity was observed in the escalation or expansion cohort.

"To see these types of responses after one treatment with bb2121 in a heavily pre-treated patient population is very promising, and we are hopeful that CAR T therapy with bb2121 may become an important therapy in the fight against multiple myeloma, which remains an insidious and incurable disease," said James Kochenderfer, M.D., the Center for Cancer Research at the National Cancer Institute in Bethesda, Maryland and a primary investigator in the study."

bb2121 is an investigational compound that is not approved for any use in any country. bb2121 recently received Breakthrough Therapy Designation from the U.S. FDA and PRIME eligibility from the EMA. Celgene has also sponsored an open-label, single-arm phase 2 study (KarMMa), which is open to recruitment, to evaluate bb2121 further in patients with relapsed/refractory multiple myeloma. (NCT03361748)

About Celgene

Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through next-generation solutions in protein homeostasis, immuno-oncology, epigenetics, immunology and neuro-inflammation. For more information, please visit www.celgene.com. Follow Celgene on Social Media: @Celgene, Pinterest, LinkedIn, Facebook and YouTube.

On December 11, 2017 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, reported initial data from the ongoing Phase 1b trial of its investigational Bruton’s Tyrosine Kinase (BTK) inhibitor, zanubrutinib (BGB-3111), in combination with its investigational anti-PD-1 antibody, tislelizumab (BGB-A317), in patients with B-cell malignancies at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, GA (Press release, BeiGene, DEC 11, 2017, View Source;p=RssLanding&cat=news&id=2322104 [SID1234522525]). The initial dose escalation data suggest that the combination of zanubrutinib and tislelizumab had a manageable toxicity profile and anti-tumor activity in patients with B-cell malignancies.

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"The initial data from this Phase 1b trial indicate that the combination of zanubrutinib and tislelizumab is tolerable with adverse events generally consistent with each therapeutic class. With only a short follow-up time, we have observed objective responses across different malignancy types in this heavily pre-treated population," commented Constantine Tam, MD, Disease Group Lead for Low Grade Lymphoma and Chronic Lymphocytic Leukemia at Peter MacCallum Cancer Centre, Director of Haematology at St. Vincent’s Hospital, Australia, and lead author of the presentation.

"Based on pre-clinical data suggesting the synergy of this combination, we are hopeful that this clinical trial will help to characterize the combination’s potential in treating patients with B-cell malignancies, particularly aggressive lymphomas," commented Jane Huang, MD, Chief Medical Officer, Hematology at BeiGene.

Summary of Results from the Ongoing Phase 1b Trial

The open-label, multi-center Phase 1b trial of zanubrutinib in combination with tislelizumab consists of a dose escalation portion to be followed by a dose expansion portion. Data presented at ASH (Free ASH Whitepaper) include patients enrolled at the first two dose levels of the dose escalation phase: dose 1 cohort of zanubrutinib at 320 mg once a day (QD) with tislelizumab at 2 mg/kg every three weeks (Q3W), and dose 2 cohort of zanubrutinib at 320 mg QD with tislelizumab at 5 mg/kg Q3W. Patients in the third dose cohort will receive zanubrutinib at 160 mg twice daily with tislelizumab at 200 mg Q3W.

As of September 15, 2017, the date of the most recent data cutoff, 25 patients, including 15 patients in the dose 1 cohort and 10 patients in the dose 2 cohort, had been enrolled. There were 13 patients with indolent lymphoma, including chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), marginal zone lymphoma (MZL), and Waldenström’s macroglobulinemia (WM), and 12 patients with aggressive lymphoma, including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and transformed lymphoma. The median follow-up time was 5.1 months (0.4-14.1 months). Two cases of autoimmune hemolysis occurred in patients with WM in the dose 2 cohort, and one qualified as a dose-limiting toxicity (DLT). These events were not associated with a positive direct antiglobulin test and resolved with immunosuppressive therapy, but resulted in the decision to exclude further enrollment of WM patients in the trial. No further DLTs were observed after WM patients were excluded.

Among patients with indolent lymphoma, the most common adverse events (AEs) (occurring in ≥ 20% of patients) of any attribution were petechiae/purpura/contusion (31%) and thrombocytopenia (23%). Grade 3-4 AEs of any attribution reported in at least two patients included thrombocytopenia, anemia, and hemolysis (15% each). Besides the two cases of autoimmune hemolysis, there was one more immune-related event, a grade 4 autoimmune encephalitis. The patient was treated with aggressive immunosuppressive therapy and gradually improved over time.

Among patients with aggressive lymphoma, the most common AEs (occurring in ≥ 20% of patients) of any attribution were diarrhea, fatigue, pyrexia, upper respiratory tract infection (33% each), cough (25%), and nausea (25%). Grade 3-4 AEs of any attribution reported in at least two patients included pyrexia (17%). There was one patient with multiple occurrences of grade 2 and 3 pneumonitis.

At the time of data cutoff, the efficacy-evaluable population consisted of 25 patients. The median follow-up time was 5.1 months (0.4-14.1 months). Objective responses were observed in 10 patients (40%). By tumor type, two partial responses (PRs) were observed out of five patients with CLL, one complete response (CR) and one PR were observed out of five patients with FL, one very good partial response and one minor response were observed out of two patients with WM, one CR was observed out of five patients with DLBCL, and three PRs were observed out of five patients with transformed lymphoma.

About Zanubrutinib

Zanubrutinib (BGB-3111) is an investigational small molecule inhibitor of BTK that has demonstrated higher selectivity against BTK than ibrutinib (a BTK inhibitor currently approved by the U.S. Food and Drug Administration and the European Medicines Agency) based on biochemical assays, higher exposure than ibrutinib based on their respective Phase 1 experience in separate studies, and sustained 24-hour BTK occupancy in both the peripheral blood and lymph node compartments.

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. It 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 high affinity and specificity for PD-1. It is 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. 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 tislelizumab for solid tumors.