On December 9, 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 preliminary clinical data from an ongoing Phase 1b trial of its investigational Bruton’s Tyrosine Kinase (BTK) inhibitor zanubrutinib (BGB-3111) in combination with the anti-CD20 antibody GAZYVA (obinutuzumab) in patients with chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (FL) at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, GA(Press release, BeiGene, DEC 9, 2017, View Source;p=RssLanding&cat=news&id=2321934 [SID1234522456]) . The updated preliminary Phase 1b data demonstrated that the combination was generally well tolerated and was highly active in patients with FL and treatment-naïve (TN) or relapsed or refractory (R/R) CLL/SLL.

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"These updated Phase 1b data continue to indicate that zanubrutinib in combination with obinutuzumab is well tolerated and highly active in patients with CLL/SLL and FL. Toxicity-related treatment discontinuation has been rare, and the rate and depth of respone in FL, as well as the rate of complete responses in CLL/SLL, is very encouraging," 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.

"We are excited to see the frequency and depth of responses in patients with CLL/SLL and R/R FL from this Phase 1b trial. We believe that these updated preliminary data continue to support our ongoing global pivotal Phase 2 trial of this combination in R/R FL," 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 obinutuzumab in patients with B-cell malignancies is being conducted in Australia, the United States, and South Korea, and consists of a dose-escalation phase and a dose-expansion phase in disease-specific cohorts, which is designed to include TN or R/R CLL/SLL and R/R FL patients. The dose-escalation component is testing zanubrutinib at 320 mg once a day (QD) or 160 mg twice daily (BID) in 28-day cycles, in combination with obinutuzumab; obinutuzumab was administered in line with standard CLL dosing (three loading doses of 1000 mg weekly followed by 1000 mg on day one of cycles 2–6). The ongoing dose-expansion component is testing doses of zanubrutinib at 160 mg BID with the same obinutuzumab schedule. As of September 15, 2017, the date of the most recent data cutoff, 45 patients with CLL/SLL and 26 patients with FL were enrolled in the trial.

At the time of data cutoff, the most common adverse events (AEs) were grade 1-2. The most common AEs in patients with CLL/SLL (occurring in ≥ 20% of patients) of any attribution were petechiae/purpura/contusion (42%), neutropenia (40%), upper respiratory tract infection (URTI) (36%), fatigue (24%), thrombocytopenia (24%), diarrhea (20%), and pyrexia (20%). The most common AEs in patients with FL (occurring in ≥ 20% of patients) of any attribution were URTI (38%), petechia/purpura/contusion (35%), rash (27%), and thrombocytopenia (23%). Grade 3 or 4 AEs of any attribution reported in ≥ 5% of the CLL/SLL patients included neutropenia (24%) and thrombocytopenia (7%). Grade 3 or 4 AEs of any attribution reported in ≥ 5% of the FL patients included neutropenia (12%). There were no cases of serious hemorrhage (≥ grade 3 hemorrhage or central nervous system hemorrhage of any grade), atrial fibrillation, or grade 3 or above diarrhea. Only one patient with CLL/SLL discontinued treatment due to an AE, a case of squamous cell carcinoma (SCC) in a patient who had a prior history of SCC. This was also the only patient in the study who had a fatal AE.

At the time of data cutoff, 45 patients with CLL/SLL (20 TN and 25 R/R) and 21 patients with R/R FL were evaluable for efficacy. In TN CLL/SLL patients, after a median follow-up of 11.4 months (6.0–17.3 months), the overall response rate (ORR) was 95% with complete responses (CRs) in 35% and partial responses (PRs) in 60% of patients. In R/R CLL/SLL patients, at a median follow-up time of 12.7 months (7.9–19.5 months), the ORR was 92% with CRs in 20% and PRs in 72% of patients. In R/R FL patients, at a median follow-up time of 12.1 months (0.8–19.7 months), the ORR was 76% with CRs in 38% and PRs in 38% of patients. ORR in high-risk CLL/SLL patients with del17p/p53 mutation (n=6), del11q mutation (n=6), and unmutated IGHV (n=19) were 83%, 100%, and 95%, respectively. The majority of patients remained on treatment at the time of data cutoff.

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.

On December 9, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that new data from the ongoing Hemlibra (emicizumab) clinical development programme were presented at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Hoffmann-La Roche, DEC 9, 2017, View Source [SID1234522459]). These data include longer-term results from the pivotal HAVEN 1 and HAVEN 2 studies in people with haemophilia A with inhibitors to factor VIII, showing once-weekly subcutaneous Hemlibra prophylaxis demonstrated superior efficacy compared to prior treatment with bypassing agents (BPAs) as prophylaxis or on-demand. These new data from the largest pivotal studies in people with haemophilia A with inhibitors further support Hemlibra as an important new treatment option for these adults, adolescents and children.

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In updated results from the HAVEN 2 study with six additional months of data and 40 more children (younger than 12 years of age), 94.7% (95% CI: 85.4; 98.9) of children with haemophilia A with inhibitors who received Hemlibra prophylaxis had zero treated bleeds (n=57). The intra-patient analysis comparing the effects of different therapies in the same child (n=13) showed a 99% reduction in treated bleeds with Hemlibra prophylaxis compared to prior treatment with a BPA, either as prophylaxis (n=12) or on-demand (n=1). Substantial improvements in health-related quality of life and aspects of caregiver burden, measured by the haemophilia-specific quality of life short form (Haemo-QoL-SF) and adapted health-related quality of life in haemophilia patients with inhibitors (Inhib-QoL) questionnaires, were also observed with Hemlibra prophylaxis compared to prior BPA prophylaxis. These data were featured today in the official press programme of the ASH (Free ASH Whitepaper) Annual Meeting.

With nearly ten additional months of follow-up, updated results from the HAVEN 1 intra-patient analysis of adults and adolescents showed an 88% (risk rate [RR]=0.12, 95% CI: 0.05; 0.28) reduction in treated bleeds with Hemlibra prophylaxis compared to prior BPA prophylaxis (n=24). The results also showed a 95% (RR=0.05, 95% CI: 0.02; 0.12) reduction in treated bleeds in patients who received Hemlibra prophylaxis compared to prior on-demand BPA treatment (n=24). After more than one year, substantially more patients continued to experience zero bleeds with Hemlibra prophylaxis compared to their prior prophylaxis or on-demand BPA treatment across bleed endpoints, including treated bleeds and all bleeds. The previously reported improvement in health status after 24 weeks, measured by the haemophilia-specific quality of life (Haem-A-QoL) and EuroQol 5-Dimensions 5-level (EQ-5D-5L) questionnaires, was also maintained with longer follow-up.

"These data demonstrate the continued reduction in bleeds over time with Hemlibra prophylaxis and reinforce the potential of this medicine, recently approved by the FDA for haemophilia A with inhibitors, to redefine the standard of care," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We are continuing to study Hemlibra in a robust clinical development programme to help advance care for all people with haemophilia A, regardless of age or inhibitor status, and provide even less frequent dosing options."

Data from the run-in cohort of the ongoing phase III HAVEN 4 study showed that Hemlibra prophylaxis dosed once every four weeks in people 12 years of age or older with haemophilia A, with or without inhibitors, resulted in levels of Hemlibra in the blood (pharmacokinetics) that were consistent with predictions. These data supported opening the expansion cohort of the study to further evaluate this dosing regimen. After a median observation time of eight weeks, 85.7% of patients (six out of seven) had zero bleeds while receiving Hemlibra prophylaxis once every four weeks. These data follow the recent announcement that an interim analysis of the phase III HAVEN 4 study showed a clinically meaningful control of bleeding in people 12 years of age or older with haemophilia A who received Hemlibra prophylaxis once every four weeks.

The most common adverse events (AEs) in the HAVEN 1 and HAVEN 2 studies at the time of these follow-up data were consistent with those observed previously in the studies. No unexpected safety findings were observed in the run-in cohort of the HAVEN 4 study. No new cases of thrombotic microangiopathy (TMA) or thrombotic events were observed in HAVEN 1, and no cases occurred in HAVEN 2 or HAVEN 4.

Based on earlier results from the HAVEN 1 and HAVEN 2 studies, Hemlibra was approved by the US Food and Drug Administration (FDA) for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children with haemophilia A with inhibitors. Data from HAVEN 1 and HAVEN 2 are also being reviewed under accelerated assessment by the European Medicines Agency (EMA) and submissions to health authorities around the world are ongoing. The clinical development programme also includes the ongoing phase III HAVEN 4 study and the phase III HAVEN 3 study, which showed a statistically significant and clinically meaningful reduction in the number of treated bleeds over time in people aged 12 years or older with haemophilia A without inhibitors who received Hemlibra prophylaxis every week or every other week, compared to those receiving no prophylaxis.

About HAVEN 1 (NCT02622321)
HAVEN 1 is a randomised, multicentre, open-label, phase III study evaluating the efficacy, safety and pharmacokinetics of once-weekly subcutaneous administration of Hemlibra prophylaxis compared to no prophylaxis in adults and adolescents with haemophilia A with inhibitors to factor VIII. The study included 113 patients (12 years of age and older) with haemophilia A with inhibitors to factor VIII, who were previously treated with BPAs on-demand or as prophylaxis. Patients previously treated with on-demand BPAs were randomised in a 2:1 ratio to receive Hemlibra prophylaxis (Arm A) or no prophylaxis (Arm B). Patients previously treated with BPAs as prophylaxis received Hemlibra prophylaxis (Arm C). Additional patients previously treated with on-demand BPAs were also enrolled in a separate arm (Arm D). On-demand treatment of breakthrough bleeds with BPAs was allowed per protocol in all arms.
The updated HAVEN 1 intra-patient analysis data presented at ASH (Free ASH Whitepaper) comparing treatment with Hemlibra prophylaxis to prior BPAs as prophylaxis or on-demand showed:

No new AEs resulted in treatment discontinuation. No new cases of TMA or thrombotic events were observed. As previously reported, three people experienced TMA events and two people experienced serious thrombotic events in the HAVEN 1 study when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate (aPCC) was administered for 24 hours or more to patients receiving Hemlibra prophylaxis.

About HAVEN 2 (NCT02795767)
HAVEN 2 is a single-arm, multicentre, open-label, clinical study in children younger than 12 years of age with haemophilia A with inhibitors to factor VIII. The study is evaluating the efficacy, safety and pharmacokinetics of once-weekly subcutaneous administration of Hemlibra prophylaxis.
The updated HAVEN 2 analysis after a median of nine weeks of treatment (range 1.6-41.6 weeks) included 60 children with haemophilia A with inhibitors to factor VIII. The updated data presented at ASH (Free ASH Whitepaper) showed:

The most common AEs related to Hemlibra were injection-site reactions. Six patients experienced serious AEs, including bleeding in the muscles (muscle haemorrhage), eye pain, catheter site infection, device-related infection, bleeding of the mouth or gums (mouth haemorrhage) and appendicitis. No cases of TMA or thrombotic events occurred in the study.

About HAVEN 4 (NCT03020160)
HAVEN 4 is a single-arm, multicentre, open-label, phase III study evaluating the efficacy, safety and pharmacokinetics (PK) of subcutaneous administration of Hemlibra dosed every four weeks. The study included 48 patients (12 years of age or older) with haemophilia A with or without inhibitors to factor VIII who were previously treated with either factor VIII or bypassing agents, on-demand or as prophylaxis.

The study was conducted in two parts: a PK run-in; and an expansion cohort. All patients in the PK run-in (n=7) were previously treated on-demand, and received subcutaneous Hemlibra at 6 mg/kg to fully characterise the PK profile after a single dose during four weeks, followed by 6 mg/kg every four weeks for at least 24 weeks. Patients in the expansion cohort (n=41) received subcutaneous Hemlibra prophylaxis at 3 mg/kg/wk for four weeks, followed by 6 mg/kg every four weeks for at least 24 weeks. Episodic treatment of breakthrough bleeds with factor VIII therapy or bypassing agents, depending on a patient’s inhibitor status, was allowed per study protocol.

About Hemlibra (emicizumab)
Hemlibra is a bispecific factor IXa- and factor X-directed antibody. It is designed to bring together factor IXa and factor X, proteins required to activate the natural coagulation cascade and restore the blood clotting process for haemophilia A patients. Hemlibra is a prophylactic (preventative) treatment that can be administered by an injection of a ready-to-use solution under the skin (subcutaneously). The clinical development programme is assessing the safety and efficacy of Hemlibra and its potential to help overcome current clinical challenges: the short-lasting effects of existing treatments, the development of factor VIII inhibitors and the need for frequent venous access. Hemlibra was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed by Chugai, Roche and Genentech. It is marketed in the United States as Hemlibra (emicizumab-kxwh) for patients with factor VIII inhibitors, with kxwh as the suffix designated in compliance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the US Food and Drug Administration.

About haemophilia A
Haemophilia A is an inherited, serious disorder in which a person’s blood does not clot properly, leading to uncontrolled and often spontaneous bleeding. Haemophilia A affects around 320,000 people worldwide,1,2 approximately 50-60% of whom have a severe form of the disorder.3 People with haemophilia A either lack or do not have enough of a clotting protein called factor VIII. In a healthy person, when a bleed occurs, factor VIII brings together the clotting factors IXa and X, which is a critical step in the formation of a blood clot to help stop bleeding. Depending on the severity of their disorder, people with haemophilia A can bleed frequently, especially into their joints or muscles.1 These bleeds can present a significant health concern as they often cause pain and can lead to chronic swelling, deformity, reduced mobility, and long-term joint damage.4 In addition to impacting a person’s quality of life,5 these bleeds can be life threatening if they go into vital organs, such as the brain.6,7 A serious complication of treatment is the development of inhibitors to factor VIII replacement therapies.8 Inhibitors are antibodies developed by the body’s immune system that bind to and block the efficacy of replacement factor VIII,9 making it difficult, if not impossible to obtain a level of factor VIII sufficient to control bleeding.

About Roche in haematology
For more than 20 years, Roche has been developing medicines that redefine treatment in haematology. Today, we are investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. In addition to approved medicines MabThera/Rituxan (rituximab), Gazyva/Gazyvaro (obinutuzumab), and Venclexta/Venclyxto (venetoclax) in collaboration with AbbVie, Roche’s pipeline of investigational haematology medicines includes Tecentriq (atezolizumab), an anti-CD79b antibody drug conjugate (polatuzumab vedotin/RG7596) and a small molecule antagonist of MDM2 (idasanutlin/RG7388). Roche’s dedication to developing novel molecules in haematology expands beyond malignancy, with the development of Hemlibra (emicizumab), a bispecific monoclonal antibody for the treatment of haemophilia A.

On December 9,2017 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported results from a leading European transplant center participating in the BP-004 trial in children with blood cancers and nonmalignant disorders (Press release, Bellicum Pharmaceuticals, DEC 9, 2017, View Source;p=RssLanding&cat=news&id=2321945 [SID1234522457]). Patients were treated with BPX-501 following an alpha/beta T cell and CD19+ B cell depleted haploidentical hematopoietic stem cell transplant (haplo-HSCT). Results demonstrated that donor BPX-501 cells infused after transplant expanded in vivo and persisted over time, contributing to improved immune recovery for patients in the study as compared to historical controls from the same transplant center. The data were reviewed in an oral presentation today during the 59th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper).

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According to study author and presenter Pietro Merli of Ospedale Pediatrico Bambino Gesù in Rome, "These data show that administering BPX-501 cells following a haplo-HSCT may result in improved immune recovery and infection control, addressing significant risks in children undergoing a stem cell transplant who do not have access to a matched donor. Adding BPX-501 to a haplo-HSCT has the potential to improve outcomes and to make the curative benefits of transplants available to more children with cancers and genetic blood diseases."

Study Design and Highlights (Abstract #211)

Investigators evaluated immune recovery and outcomes of 112 pediatric patients who underwent a haplo-HSCT followed by treatment with BPX-501. Children in the study had acute leukemia (n=53), Primary Immune Deficiencies (n=26), erythroid disorders (n=17), Fanconi anemia (n=7), and other diseases (n=9). All patients were transplanted after depletion of donor alpha/beta T cells and CD19 B cells to prevent graft-versus-host disease (GvHD) and post-transplant lymphoproliferative disorders (PTLD). BPX-501 cells were scheduled to be infused approximately two weeks post-transplant.

Results showed:

BPX-501 cells infused after haplo-HSCT expand and persist in patients, potentially contributing to improved recovery of adaptive immunity.
Peak expansion of BPX-501 cells is reached at nine months after infusion, and BPX-501 cells are consistently detected after two years.
CMV infection is a main driver of BPX-501 cell expansion, suggesting that BPX-501 cells cooperate in clearing the viral infection.
The overall pattern of immune recovery in 112 children studied may be improved when compared to patients who received a similar haplo-HSCT without BPX-501.
"Improved immune recovery and control over infections, as demonstrated in this study, may have a direct impact on treatment-related morbidity and mortality," commented Rick Fair, Bellicum’s President & Chief Executive Officer. "We look forward to reporting on these and other outcomes from our ongoing BP-004 trial in 2018."

A copy of the ASH (Free ASH Whitepaper) presentation will be made available in the "Investors & Media" section of the Company’s website.

About BPX-501
BPX-501 is an adjunct T cell therapy administered after allogeneic HSCT, comprising genetically modified donor T cells incorporating Bellicum’s CaspaCIDe safety switch. It is designed to provide a safety net to eliminate alloreactive BPX-501 T cells (via administration of activator agent rimiducid) should uncontrollable GvHD occur. This enables physicians to more safely perform stem cell transplants by administering BPX-501 engineered T cells to speed immune reconstitution, provide control over viral infections and enhance Graft-versus-leukemic effect without unacceptable GvHD risk. The ongoing BP-004 clinical study of BPX-501 is being conducted at transplant centers in the U.S. and Europe.

On December 9, 2017 Fate Therapeutics, Inc. (NASDAQ:FATE), a biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported the generation of chimeric antigen receptor (CAR)-targeted CD8αβ+ T cells from a clonal engineered master pluripotent cell line (MPCL) (Press release, Fate Therapeutics, DEC 9, 2017, View Source [SID1234522462]). The clonal engineered MPCL was created from an induced pluripotent stem cell (iPSC), which was modified in a one-time engineering event using CRISPR/Cas9 to both insert a CAR into the T-cell receptor α constant (TRAC) locus and eliminate T-cell receptor (TCR) expression. The groundbreaking development enables the renewable production of CAR-targeted, TCR-null CD8αβ+ T cells that are not restricted to an individual patient for off-the-shelf administration.

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The breakthrough was reported today at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition by scientists from the laboratories of Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering, Memorial Sloan Kettering Cancer Center and Fate Therapeutics. In September 2016, Fate Therapeutics and Memorial Sloan Kettering Cancer Center launched a multi-year partnership led by Dr. Sadelain to develop off-the-shelf T-cell product candidates using clonal engineered MPCLs. The collaborators are currently conducting preclinical studies and finalizing current good manufacturing practice protocols for the development of CAR-targeted, TCR-null T-cell immunotherapies. A first-in-human clinical trial of FT819, a CAR19 T-cell product candidate derived from a clonal engineered MPCL with complete elimination of TCR expression and TRAC-regulated CAR expression, is being planned.

"The use of a clonal engineered master pluripotent cell line enables cost-effective manufacture, timely availability and reliable off-the-shelf delivery of targeted T-cell cancer immunotherapy without patient restriction," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "Additionally, unlike conventional allogeneic CAR T-cell approaches that involve billions of heterogeneous engineering events to modify the genomic function of primary T cells, an engineered iPSC clone is defined by a single uniform engineering event. As a result, a T-cell product generated from a clonal engineered master pluripotent cell line is homogeneous with respect to genomic modification and cell product composition. This revolutionary approach has the potential to mediate safer, more effective pharmacologic activity, including in combination with cycles of other cancer treatments."

In February 2017, Dr. Sadelain and colleagues published a set of preclinical studies in the journal Nature using primary T cells demonstrating that directing a CD19-specific CAR to the TRAC locus with CRISPR/Cas9 resulted in uniform CAR expression and enhanced T-cell potency as compared to conventional CAR T cells. Scientists from the laboratories of Sadelain and Fate Therapeutics advanced the observation by instead engineering iPSCs and generating CD8αβ+ T cells from a clonal engineered MPCL with a CD19-targeted CAR inserted into the TRAC locus and complete elimination of TCR expression. The collaborators demonstrated that the CAR-targeted, TCR-null CD8αβ+ T cells display antigen-specific anti-tumor potency, including cytokine release and targeted cellular cytotoxicity.

Fate Therapeutics has built an extensive intellectual property portfolio broadly covering the genomic engineering of iPSCs and off-the-shelf engineered T- and NK cell cancer immunotherapies. Its proprietary portfolio includes compositions and methods for editing iPSCs to modify their biological properties using CRISPR and other nucleases, including the use of CRIPSR to insert a CAR in the TRAC locus for endogenous transcriptional control, and for manufacturing cells of all hematopoietic lineages from iPSCs including T cells. In addition, the Company has an exclusive license from Memorial Sloan Kettering covering iPSC-derived T cells expressing chimeric antigen receptors for human therapeutic use, and maintains an option to exclusively license intellectual property arising from all research and development activities under the collaboration.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables large-scale generation of off-the-shelf, engineered, homogeneous cell products that can be administered in repeat doses to mediate more effective pharmacologic activity. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event, and selecting a single iPSC for maintenance as a clonal master pluripotent cell line (MPCL). Similar to master cell lines used for the manufacture of monoclonal antibodies, clonal MPCLs can serve as a renewable cell source for the consistent and repeated manufacture of homogeneous cell products with the potential to treat many different diseases and many thousands of patients in an off-the-shelf manner. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 90 issued patents and 100 pending patent applications.

On December 9, 2017 Amphivena Therapeutics Inc., a privately held biotechnology company developing AMV564, a CD33/CD3 T cell redirector for the treatment of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), reported that it will present in an oral presentation at the 59th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) preclinical data that demonstrate that treatment with AMV564 selectively depletes myeloid-derived suppressor cells (MDSCs) in bone marrow cells from patients with MDS with resultant reactivation of T lymphocytes (Press release, Amphivena Therapeutics, DEC 9, 2017, View Source [SID1234522520]). AMV564-induced restoration of immune homeostasis was accompanied by a significant improvement in hematopoiesis. AMV564 is a CD33/CD3 bivalent bispecific antibody that binds both CD33 and CD3 with strong avidity and results in T-cell directed lysis of CD33-expressing myeloid cells.

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"These preclinical data provide a strong rationale for clinical investigation of this innovative approach in patients with MDS, who have limited treatment options today. The data also underscore an opportunity to develop AMV564 for patients with other malignancies where MDSCs have been shown to contribute to the immunosuppressive tumor microenvironment," said Eric J. Feldman, M.D., Amphivena’s Senior Vice President, Clinical Development.

Alan List, M.D., President and CEO of Moffitt Cancer Center, who presented on behalf of the investigators, said, "AMV564 eliminated CD33+ MDSCs in a dose-dependent manner and restored critical aspects of immune homeostasis. In addition, proliferation of CD4+ and CD8+ T cells more than doubled with AMV564 treatment as compared to baseline; IFN-γ production, as measured by gene expression, markedly increased in AMV564-treated cells. AMV564-directed elimination of MDSCs was associated with decreased DNA damage in CD34+ stem cells and improved colony-forming capacity. Finally, the presentation concluded, AMV564 and anti-PD-1 treatment are synergistic for T-cell activation."

Amphivena plans to launch a Phase 1 clinical study in patients with MDS in early 2018. Currently, the company is conducting a Phase 1 clinical study of AMV564 in relapsed or refractory AML and is also exploring the utility of AMV564 in solid tumors.