On December 5, 2016 Bellicum Pharmaceuticals, Inc. (Nasdaq: BLCM), a clinical stage biopharmaceutical company focused on discovering and developing novel cellular immunotherapies for cancers and orphan inherited blood disorders, reported the presentation of preclinical results on the Company’s GoCAR-T and GoTCR technologies at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California (Press release, Bellicum Pharmaceuticals, DEC 5, 2016, View Source;p=RssLanding&cat=news&id=2227609 [SID1234516934]).

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!

"We are pleased to report further supportive preclinical data on the utility of our proprietary iMC activation switch, which is incorporated into our BPX-601 GoCAR-T product candidate now entering a Phase 1 clinical study," commented Tom Farrell, President and CEO of Bellicum Pharmaceuticals. "We believe our novel technology provides a powerful and unique solution for overcoming the efficacy and safety challenges of T-cell therapies, especially when targeting solid tumors."

The Company’s GoCAR-T platform incorporates an inducible MyD88/CD40 (iMC) costimulatory switch, which requires presence of both a target antigen and rimiducid to trigger the full effect of CAR T cell activity. The presence of rimiducid and antigen results in upregulation of cytokines such as IL2, leading to T-cell proliferation, persistence and improved anti-tumor efficacy. Unlike traditional CAR T constructs, GoCAR-T is designed to support persistence of CAR T cells in the body in the absence of cancer antigen to provide continued anti-tumor surveillance.

In a poster presentation titled, "Inducible MyD88/CD40 (iMC) Costimulation Provides Ligand-Dependent Tumor Eradication By CD123-Specific Chimeric Antigen Receptor T Cells," Bellicum scientists targeted CD123, which is highly expressed in acute myeloid leukemia (AML) and leukemic stem cells. Results demonstrated that GoCAR-T removed CD123-positive leukemic cells in animal models through rimiducid-activated costimulation. Conversely, infrequent costimulation with rimiducid led to reduced activity of CAR T cells, supporting the technology’s potential to provide control over the activation, expansion and persistence of cells to achieve a desired level of safety and anti-tumor potency.

Additional data were presented on the Company’s GoTCR technology, which also uses an iMC costimulatory switch. The presence of GoTCR and rimiducid triggers the release of cytokines that upregulate MHC (major histocompatibility complex) on tumor cells, exposing them to potent immune response by both engineered and endogenous T cells. In the study outlined in a poster presentation titled, "Inducible MyD88/CD40 (iMC) Enhances Proliferation and Survival of Tumor-Specific TCR-Modified T Cells and Improves Anti-Tumor Efficacy in Myeloma," T cells were engineered to express tumor antigen-specific T-cell receptors (TCRs) targeting preferentially-expressed antigen in melanoma (PRAME) or Bob1. PRAME is overexpressed in a wide variety of cancers including melanoma, sarcoma and several types of leukemias. Bob1 is also found to be highly expressed in certain leukemias, along with lymphomas and myelomas. Results demonstrated that the rimiducid-driven iMC costimulatory switch provided potent T-cell activation, proliferation and persistence, synergizing with signals from PRAME- or Bob1-targeted TCRs for improved anti-tumor efficacy in vitro and in vivo.

On December 5, 2016 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that preclinical data on IMGN632, a novel CD123-targeting ADC, were presented today at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, CA (Press release, ImmunoGen, DEC 5, 2016, View Source [SID1234516935]).

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!

CD123 is an attractive target due to its elevated expression in acute myeloid leukemia (AML). IMGN632 uses ImmunoGen’s new family of indolino-benzodiazepine cancer-killing agents, called IGNs. ImmunoGen designed IGNs to be highly potent and to alkylate DNA without crosslinking it. Specifically, IMGN632 uses the Company’s DGN549 payload and incorporates novel linker and conjugation technology.

"We developed our DNA-alkylating IGN payloads to meet the dual challenges of achieving high potency against target cells, while having a tolerability profile that enables continued patient treatment," said Richard Gregory, Ph.D., Executive Vice President and Chief Scientific Officer of ImmunoGen. "These preclinical data demonstrate that IMGN632 has the potential for broad and potent activity in patients with AML and an improved tolerability profile."

The data presented at ASH (Free ASH Whitepaper) (oral abstract #768) compared IMGN632, an ADC with an alkylating IGN, to a version of IMGN632 with a crosslinking payload. In vitro cytotoxic activity was compared in multiple AML cell lines. Both ADCs were found to be highly active against AML cells, including those with poor prognostic markers (FLT3-ITD, P53, MDR1), and were approximately 100-fold more active on AML patient samples than gemtuzumab ozogamicin.

Both ADCs exhibited similar efficacy in human AML xenograft models; however, the effects of the ADCs in toxicity studies were very different. While IMGN632, the alkylating ADC, was well tolerated at the dose tested, the crosslinking ADC showed persistent delayed toxicity (weight loss) at less than half the dose.

In addition, on normal bone marrow cells, IMGN632 was approximately 50-fold less toxic than the crosslinking ADC, while retaining high potency against AML cells.

These results show that IMGN632 has potent selective activity against AML cells with lower cytotoxicity to normal myeloid progenitor cells than an ADC designed to crosslink DNA activity. These data suggest IMGN632 has the potential to be a highly potent yet tolerable ADC for AML patients.

Supporting preclinical data were also presented at ASH (Free ASH Whitepaper) in which IMGN632 showed compelling activity in AML xenograft models (abstract #2832).

The Company plans to submit an IND application and initiate clinical testing of IMGN632 in 2017.

Preclinical data were also presented at ASH (Free ASH Whitepaper) on IMGN779, a potent CD33-targeting ADC using an IGN payload, (abstract #1645) from a combination study of IMGN779 with a PARP inhibitor (olaparib). The data demonstrated enhanced activity in several AML models including patient derived tumor cells and a disseminated AML xenograft model. IMGN779 is currently being evaluated in a Phase 1 study as a monotherapy in AML.

About Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a cancer of the bone marrow cells that produce white blood cells. It causes the marrow to increasingly generate abnormal immature white blood cells (blasts) that do not mature into effective infection-fighting cells. The blasts quickly fill the bone marrow, impacting the production of normal platelets and red blood cells. The resulting deficiencies in normal blood cells leave the patient vulnerable to infections, bleeding problems and anemia.

In 2016, it is estimated that nearly 20,000 new cases of AML will be diagnosed in the U.S. and more than 10,000 people will die from the disease.1

On December 6, 2016 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported updated safety and efficacy data from an ongoing phase 1/2a clinical study evaluating MOR202 alone and in combination with immunomodulatory drugs (IMiDs) lenalidomide (Len) and pomalidomide (Pom), plus dexamethasone (Dex), in heavily pre-treated patients with relapsed/refractory multiple myeloma (MM) (Press release, MorphoSys, DEC 5, 2016, View Source [SID1234516958]). MOR202 is an investigational human antibody targeting CD38 . Data were presented during an oral presentation at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California/USA.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The results presented include updated data from higher dosing cohorts of MOR202 in combination with IMiDs, in patients being evaluable for efficacy and safety assessment. In addition to the infusion time of 2 hours and the occurrence of infusion-related reactions in only 7% of the patients, we are particularly pleased with the responses seen in patients treated with MOR202 plus Len/Dex and Pom/Dex", Dr. Arndt Schottelius, Chief Development Officer of MorphoSys AG, commented. "We look forward to enrolling more patients in the highest dosing cohorts of 16 mg/kg MOR202 in these combinations."

Patients treated with MOR202 in combination with Len/Dex had a median of 2 prior regimens; 64% were refractory to their last therapy. In this arm of the trial, 91% of evaluable patients (10 out of 11) showed an objective response (defined as either a complete response (CR) or a partial response (PR)) to MOR202 and Len/Dex. Considering only patients in the highest dosing cohort of 16mg/kg MOR202 plus Len, ORR (objective response rate) was 100%, with 7 out of 7 patients showing response to treatment.

In the group receiving MOR202 with Pom/Dex, patients had a median of 3 prior therapies, all being refractory to their last therapy. In these heavily pretreated patients, 57% (4 out of 7) showed a response, with two patients achieving a complete remission (CR). In relapsed/refractory patients treated with MOR202 alone, 29% (5 out of 17) showed an objective response.

Responses are ongoing in 16 of 19 patients, with the longest response ongoing for more than 14 months. The median progression-free survival (PFS) of the patients treated with MOR202 alone was 4.7 months; the median PFS for the combination regimen has not yet been reached.

MOR202 was given as a 2-hour infusion up to the highest dose of 16 mg/kg. Infusion-related reactions (IRRs) occurred in 7% of patients and were limited to grade 1 or 2. The most frequent adverse events of grade 3 or higher were lymphopenia, neutropenia and leukopenia. No unexpected safety signals were observed. No treatment-related deaths were reported.

According to a biomarker analysis, CD38 molecules were preserved on bone marrow plasma cells during MOR202 treatment, comparing values at baseline and at cycle 2 day 1.

Number und tittle of the presentation:
Abstract #1152
Raab et al: A Phase I/IIa Study of the CD38 Antibody MOR202 Alone and in Combination with Pomalidomide or Lenalidomide in Patients with Relapsed or Refractory Multiple Myeloma

MorphoSys held an Investor & Analyst Event at the 2016 ASH (Free ASH Whitepaper) Annual Meeting on December 5, 2016, at 8:00pm PST (December 6, 2016: 4:00am GMT, 5:00am CET). Two clinical investigators presented clinical data for MorphoSys’s investigational agents MOR208 and MOR202.
A replay and the presentation will be made available at View Source
Webcast: View Source

About MOR202 and the ongoing phase 1/2a study in multiple myeloma
The investigational drug MOR202 is a fully human HuCAL antibody targeting CD38, a highly expressed and validated target in multiple myeloma. Data are from an ongoing clinical phase 1/2a, open-label, multi-center, dose-escalation study conducted in several sites in Germany and Austria. The study is evaluating the safety and preliminary efficacy of MOR202 alone and in combination with the immunomodulatory drugs pomalidomide (Pom) and lenalidomide (Len) plus dexamethasone (Dex) in patients with relapsed/refractory multiple myeloma. The primary endpoints of the trial are the safety, tolerability and recommended dose of MOR202 alone and in combination with the IMiDs. Secondary outcome measures are pharmacokinetics and preliminary efficacy based on overall response rate, duration of response, time-to-progression, and progression-free survival.

On December 5, 2016 Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to treat cancer, reported the presentation of results from the DYNAMO study, a Phase 2 clinical trial evaluating the safety and efficacy of duvelisib in patients with indolent non-Hodgkin lymphoma (iNHL) that is double refractory to both rituximab and chemotherapy, at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2016 Annual Meeting held December 3-6, 2016 in San Diego (Press release, Verastem, DEC 5, 2016, View Source;p=RssLanding&cat=news&id=2227733 [SID1234516975]). Duvelisib is an investigational, oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma that has demonstrated clinical activity as a monotherapy in multiple hematologic cancers, including chronic lymphocytic leukemia (CLL), iNHL and T cell lymphomas.

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!

Results from the study were presented by Dr. Ian Flinn in an oral presentation, "DYNAMO: A phase 2 study demonstrating the clinical activity of duvelisib in patients with refractory indolent non-Hodgkin lymphoma." (Abstract number: 1218) Ian Flinn, M.D., Ph.D., Director of the Blood Cancer Research Program at Sarah Cannon Research Institute and the principal investigator on the DYNAMO study, described the results demonstrating duvelisib’s clinical activity in patients with double refractory iNHL, which included robust and durable responses, and a manageable safety profile.

The DYNAMO study included 129 evaluable patients with double refractory iNHL (median 3 prior anticancer regimens, range 1-18). The overall response rate (ORR) was 46% as determined by independent review committee (IRC; p=0.0001; 95% CI 0.37-0.55). Among disease subgroups, the ORR was 41% in follicular lymphoma (n=83), 68% in small lymphocytic lymphoma (n=28), and 33% in marginal zone lymphoma (n=18). Median duration of response (DOR) among all patients was 9.9 months. Notably, 83% of patients had reductions in the size of their target lymph nodes per IRC.

Duvelisib was generally well tolerated, with an expected and manageable safety profile with appropriate risk mitigation. The most common Grade ≥3 adverse events (occurring in ≥10% of patients) included neutropenia (28%), infection (18%), diarrhea (15%), thrombocytopenia (13%) and anemia (12%).

Dr. Flinn commented, "These results from the DYNAMO study presented at ASH (Free ASH Whitepaper) this year clearly show that duvelisib is clinically active with benefit observed across a variety of disease subtypes. It is important to recognize how heavily pre-treated the DYNAMO patients were, being refractory to both rituximab and chemotherapy. This patient population needs more treatment options."

"We are very encouraged by these results," said Gregory I. Berk, M.D., Chief Medical Officer of Verastem. "The activity and safety of duvelisib observed in the DYNAMO trial are just more evidence of the potential of this drug. We are committed to continuing duvelisib’s development with the belief that it may represent a valuable treatment for patients with very few treatment options."
A copy of the DYNAMO oral presentation is available here.

The following is a summary of other presentations at ASH (Free ASH Whitepaper) 2016:
Poster Presentations
Title: Preliminary results in first-line treatment of follicular lymphoma with the oral dual PI3K-delta,gamma inhibitor, duvelisib, in combination with rituximab or obinutuzumab
Lead Author: Carla Casulo, M.D., Assistant Professor, Wilmot Cancer Institute, University of Rochester
Abstract Number: 2979
Date and Time: Sunday, December 4, 2016, 6:00 – 8:00 pm PT
The poster can be viewed here.
Title: Inhibition of FAK Exerts Anti-Leukemic Activity and Potentiates ABT-199-Induced Apoptosis in AML
Lead Author: Bing Carter, Ph.D., Associate Professor, Department of Leukemia – Research, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center
Abstract Number: 1574
Date and Time: Saturday, December 3, 2016, 5:30 – 7:30 pm PT
The poster can be viewed here.

More About the Phase 2 DYNAMO Study
The DYNAMO study is a Phase 2, single-arm study which evaluated the efficacy and safety of duvelisib (25 mg twice daily) as a monotherapy in 129 patients with follicular lymphoma (n=83), small lymphocytic lymphoma (n=28) or marginal zone lymphoma (n=18) whose disease has progressed and who are refractory to rituximab and to either chemotherapy or radioimmunotherapy. The primary endpoint of the study was overall response rate as assessed by an independent review committee.

About the Tumor Microenvironment
The tumor microenvironment encompasses various cellular populations and extracellular matrices within the tumor or cancer niche that support cancer cell survival. This includes immunosuppressive cell populations such as regulatory T cells, myeloid-derived suppressor cells, M2 tumor-associated macrophages, as well as tumor-associated fibroblasts and extracellular matrix proteins which can hamper the entry and therapeutic benefit of cytotoxic immune cells and anti-cancer drugs. In addition to targeting the proliferative and survival signaling of cancer cells, Verastem’s compounds duvelisib and defactinib target the tumor microenvironment as a mechanism of action to potentially improve a patient’s response to therapy.

About Duvelisib
Duvelisib is an investigational, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes that are known to help support the growth and survival of malignant B cells and T cells. PI3K signaling may lead to the proliferation of malignant B cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 Duvelisib is currently being evaluated in late- and mid-stage clinical trials, including DUO, a randomized, Phase 3 monotherapy study in patients with relapsed/refractory chronic lymphocytic leukemia (CLL)4, and DYNAMO, a single-arm, Phase 2 monotherapy study in patients with refractory indolent non-Hodgkin lymphoma (iNHL) that achieved its primary endpoint of overall response rate upon topline analysis of efficacy data5. Duvelisib is also being evaluated for the treatment of hematologic malignancies through investigator-sponsored studies, including T cell lymphoma.6 Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.

About Defactinib
Defactinib (VS-6063) is an investigational inhibitor of Focal Adhesion Kinase (FAK), a non-receptor tyrosine kinase encoded by the PTK-2 gene that mediates oncogenic signaling in response to cellular adhesion and growth factors.7 Based on the multi-faceted roles of FAK, defactinib is used to treat cancer through modulation of the tumor microenvironment, enhancement of anti-tumor immunity, and reduction of cancer stem cells.8,9 Defactinib is currently being evaluated in three separate clinical collaborations in combination with immunotherapeutic agents for the treatment of several different cancer types including pancreatic, ovarian, non-small cell lung cancer, and mesothelioma. These studies are combination clinical trials with pembrolizumab and avelumab from Merck & Co. and Pfizer/Merck KGaA, respectively.10,11,12 Information about these and additional clinical trials evaluating the safety and efficacy of defactinib can be found on www.clinicaltrials.gov.

On December 5, 2016 TG Therapeutics, Inc. (NASDAQ:TGTX), reported the presentation of combination data from a Phase 1b study evaluating TGR-1202, the Company’s once-daily PI3K delta inhibitor, in combination with ibrutinib, the oral Bruton’s tyrosine kinase (BTK) (Press release, TG Therapeutics, DEC 5, 2016, View Source [SID1234516937]). This study is being run in collaboration with the Blood Cancer Research Partnership (BCRP) and Dana-Farber Cancer Institute (DFCI), Boston, MA. Data from this trial were presented today by the Principal Investigator, Matthew S. Davids, MD, of Dana-Farber Cancer Institute, during an oral session at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in San Diego, CA.

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!

Michael S. Weiss, the Company’s Executive Chairman and Interim CEO commenting on the data said, "We and our investigators continue to be impressed with the ease of combining TGR-1202 with other novel agents. Here Dr. Davids demonstrated that the double blockade of the BCR pathway with dual oral once-daily inhibitors can be performed safely and conveniently, and derives high response rates in patients with both CLL and MCL. This all oral approach offers a unique and highly active alternative for patients who do not want to receive infused therapies but still want to advance their treatment beyond single agent ibrutinib, which may offer multiple benefits over single agent therapy. With one bone marrow confirmed complete response (CR) and 5 additional deep responses nearing radiographic CR out of the 17 evaluable CLL patients, we and our investigators believe we are seeing activity beyond what one might expect from either of these agents alone. We want to thank Dr. Davids and his collaborators at DFCI and the Leukemia & Lymphoma Society for providing support for this important investigator driven research and we look forward to follow-up data in the future from this study and data from our own triple therapy of TG-1101 plus TGR-1202 plus ibrutinib, which we are targeting for presentation next year."

The following summarizes the key highlights from this oral presentation which occurred today:

Oral Presentation: TGR-1202 in Combination with Ibrutinib in Patients with Relapsed or Refractory CLL or MCL: Preliminary Results of a Multicenter Phase I/Ib Study (Abstract Number 641)

This oral presentation includes data from patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) treated with TGR-1202 in combination with Ibrutinib. 31 patients were evaluable for safety (18 CLL patients and 13 MCL patients), of which 28 patients were available for efficacy (17 CLL patients and 11 MCL patients.) CLL patients had a median of 1.5 prior lines of therapy (range 1-6), with 2 patients receiving prior ibrutinib and 4 receiving prior PI3K inhibitors. MCL patients had a median of 3 prior lines of therapy (range 2-5), with 2 patients also receiving prior ibrutinib.

Highlights from this oral presentation include:

88% (15 of 17) Overall Response Rate (ORR) (including Complete Response (CR), Partial Response (PR), and Partial Response with lymphocytosis (PR-L)) in patients with CLL, with 1 patient achieving a bone marrow confirmed CR and 5 patients with a > 80% nodal reduction, nearing radiographic CR
1 year progression free survival (PFS) and overall survival (OS) for CLL is 94% (n=17), with the longest patient on study approaching two years
73% (8/11) ORR in patients with MCL, with clinical benefit observed in two additional patients
1 year PFS and OS for MCL is 37% and 52%, respectively (n=11)
The combination appears well tolerated across all patients with no grade 3/4 transaminitis (liver toxicity), diarrhea, colitis or pneumonitis observed
PRESENTATION DETAILS:

The above referenced presentation is available on the Company’s website at www.tgtherapeutics.com, located on the Publications page.