2015 Post-ASH Report

Datamonitor Healthcare Trialtrove Biomedtracker Pharma intelligence | Pharma intelligence | Pharma intelligence |

RACHEL MEIGHAN-MANTHA Principal Analyst, Citeline

JOSEPH HEDDEN Senior Analyst, Datamonitor Healthcare

Summary

Profiled themes at the 57th Annual Meeting and Exposition of the American Society of Hematology (ASH), held December 5-8, 2015, in Orlando, Florida, included Genomic Profiling and Chemical Biology, Genome Editing and Gene Therapy, Epigenetic Mechanisms, Immunologic Treatments, Stem Cell Biology and Regenerative Medicine and Preventing Venous Thromboembolic Disease. This report will mainly focus on the theme of Immunologic Treatments because of the importance and popularity of immunotherapies for many different hematological cancers.

Also covered in this report are the results from pivotal trials presented at ASH, as well as highlights from other drugs/therapies of interest. In addition, we felt it was important to cover first-in-human trials since (hopefully) some of these drugs/therapies will be in pivotal trials in a few years. At the end of the report, we’ve included a section showcasing drugs that had top- line results presented at ASH, followed by a list of other data presentations supplied by BioMedTracker (BMT). Accompanying links to BioMedTracker events along with changes to the drugs’ likelihood of approval (LOA) are also provided throughout the report. Finally, additional supplemental material related to ASH is listed in the Appendix.

Datamonitor Healthcare Trialtrove Biomedtracker 2 Pharma intelligence | Pharma intelligence | Pharma intelligence | Contents

Advancements in Immuno-Oncology 4 CAR-T Cell Therapies 4 CAR-BCMA for Multiple Myeloma 4 CTL019 for Diffuse Large B-Cell Lymphoma (DLBCL) - NHL 5 JCAR014 for Hematologic Cancer 6 CD30.CARTs for CD30+ Hodgkin and Non-Hodgkin Lymphomas 6 CTL019 for Acute Lymphocytic Leukemia (ALL) 7 JCAR015 for Acute Lymphocytic Leukemia (ALL) 8 CTL119 for CD19+ Acute Lymphocytic Leukemia (ALL) 8 KTE-C19 for Acute Lymphocytic Leukemia (ALL) 9 KTE-C19 for Indolent Non-Hodgkin's Lymphoma - NHL 9 CAR-T Cell Therapy Trials in Hematological Malignancies 10 Advancements in PD-1 Development 11 Opdivo for Hodgkin's Lymphoma 12 Keytruda for Hodgkin's Lymphoma 12 Keytruda for Chronic Lymphocytic Leukemia (CLL)/Small Cell Lymphocytic 14 Lymphoma (SLL) - NHL Keytruda for Multiple Myeloma (MM) 15

Other Key Immunotherapy Data 16 Darzalex for Multiple Myeloma (MM) 16 Empliciti for Multiple Myeloma (MM) 17 Other Drugs/Therapies of Interest 19 Zydelig for Chronic Lymphocytic Leukemia (CLL)/Small Cell Lymphocytic 19 Lymphoma (SLL) - NHL Acalabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Cell 20 Lymphocytic Lymphoma (SLL) - NHL Pivotal Trials 21 Midostaurin for Acute Myelogenous Leukemia (AML) 21 Imbruvica for Chronic Lymphocytic Leukemia (CLL)/Small Cell 22 Lymphocytic Lymphoma (SLL) - NHL Ninlaro for Multiple Myeloma (MM) 24 First-in-Human in Hematological Malignancies 26 Top-Line Results Presented at ASH 28 Additional Results Presented at ASH 31 Appendix: Additional ASH Content 38

Datamonitor Healthcare Trialtrove Biomedtracker 3 Pharma intelligence | Pharma intelligence | Pharma intelligence | Advancements in Immuno-Oncology

CAR-T Cell Therapies

CAR-T cell therapies certainly generated lots of interest this year at ASH based on audience numbers in the sessions where these therapies were presented. However, in contrast to the euphoria generated at previous ASH meetings, the focus this year was directed towards practical issues associated with using CAR-T cell therapies. Results still generated continued interest but this excitement was tempered by persistent issues of safety, durability of response, relapse and manufacturing. Highlights of several presentations are covered in the tables below.

CAR-BCMA for Multiple Myeloma

Remissions of Multiple Myeloma during a First-in-Humans Clinical Trial of T Cells Expressing an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor (Abstract #LBA1)

Primary CAR-BCMA Disease r/r BCMA+ MM Trial ID NCT02215967 Drug Sponsor NCI Treatment Cy/Flu lymphodepletion before CAR-BCMA infusion (0.3 – 9 x 106 T cells/kg) 12 pts; 1 stringent CR in high disease burden pt Results 2-10+ wk DOR Substantial but reversible toxicity A bluebird bio Phase I trial with a similar BCMA-CAR-T candidate (bb2121) is Comment expected to begin enrollment in early 2016. Dr. Kochenderfer will serve as one of the principal investigators for this trial.

Datamonitor Healthcare Trialtrove Biomedtracker 4 Pharma intelligence | Pharma intelligence | Pharma intelligence | CTL019 for Diffuse Large B-Cell Lymphoma (DLBCL) - NHL

Phase IIa – NHL (Penn) Change to BMT LOA: 0%

Sustained Remissions Following Chimeric Antigen Receptor Modified T Cells Directed Against CD19 (CTL019) in Patients with Relapsed or Refractory CD19+ Lymphomas (Abstract #183)

Primary CTL019 Disease r/r Adult CD19+ NHL Trial ID NCT02030834 Drug Sponsor University of Pennsylvania-Abramson/Novartis Treatment Lymphodepletion d-4 to d-1 before CTL019 infusion (1-5 x 108 T cells/kg)

43 pts; DLBCL = 26, FL = 14 and MCL = 3; 30/43 pts infused DLBCL (n = 15): 3 mo ORR 47%; 3 CR at 3 mo – 6 CR at 6 mo; mPFS 3 mo Results FL (n = 11): 3 mo ORR 73%; 4 CR at 3 mo – 7 CR at 6 mo; mPFS not reached No relapses observed for CR pts CRS generally Grade 2 Response, improvement of response after infusion and duration of response Comment look most promising in follicular lymphoma patients.

Datamonitor Healthcare Trialtrove Biomedtracker 5 Pharma intelligence | Pharma intelligence | Pharma intelligence | JCAR014 for Hematologic Cancer

Phase I/II – NHL/CLL/ALL Change to BMT LOA: 0%

Anti-CD19 Chimeric Antigen Receptor-Modified T Cell Therapy for B Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Fludarabine and Cyclophosphamide Lymphodepletion Improves In Vivo Expansion and Persistence of CAR-T Cells and Clinical Outcomes (Abstract #184)

Primary Adult, CD19+ B-cell JCAR014 Disease Trial ID NCT01865617 Drug NHL, CLL and ALL Sponsor University of Washington - Fred Hutchinson Lymhodepletion (Cy, Cy/E or Cy/Flu) d-4 to d-2 before 1:1 CD4+:CD8+ Treatment JCAR014 infusion (2 x 105 – 107 T cells/kg) NHL 32 pts: 63% CRS (13% severe); 25% Grade 3/4 neurotoxicity Cy/Flu lymphodepletion improved CAR-T cell expansion and persistence, Results reduced transgene immune responses and enabled responses to 2nd infusion non-Cy/Flu: 50% ORR / 8% CR vs. Cy/Flu: 72% ORR / 50% CR CLL 9 pts: 89% ORR / 44% CR Promising results for heavily pretreated patients (median of five prior Comment therapies). Beneficial effects of balanced CD4+/CD8+ CAR-T cells and Cy/Flu lymphodepletion need to be confirmed.

CD30.CARTs for CD30+ HL and NHL

Chimeric T Cells for Therapy of CD30+ Hodgkin and Non-Hodgkin Lymphomas (Abstract #185)

Primary CD30.CARTs Disease CD30+ HL and NHL Trial ID NCT01316146 Drug Sponsor Baylor College Treatment 3 DLs: 2 x 107 – 2 x 108 T cells/m2 (no prior lymphodepletion) 9 pts; 2 CR and 1 PR to date Results Viral immunity not comprised in pts Larger patient population is needed to confirm results. Presenter concluded Comment adequate lymphodepletion is needed for CAR-T cell expansion.

Datamonitor Healthcare Trialtrove Biomedtracker 6 Pharma intelligence | Pharma intelligence | Pharma intelligence | CTL019 for Acute Lymphocytic Leukemia (ALL)

Phase II – Pediatric (UPenn) Change to BMT LOA: 0%

Durable Remissions in Children with Relapsed/Refractory ALL Treated with T Cells Engineered with a CD19-Targeted Chimeric Antigen Receptor (CTL019) (Abstract #681)

Primary CTL019 Disease r/r Pediatric CD19+ ALL Trial ID NCT02228096 Drug Sponsor University of Pennsylvania - Abramson/Novartis Treatment Lymphodepletion 1 wk before CTL019 infusion (107 to 108 T cells/kg) 59 pts; 55 CR (93%); 6 mo RFS: 76%; 12 mo RFS: 55%; 12 mo OS: 79%; 18 pts in remission beyond 1 yr Response similar in MRD+ or MRD- pts IL-6 levels correlated with severe cytokine release syndrome (CRS) Results CRS in 88 % of pts - severity related to disease burden CD19+ relapse highly enriched in pts that lose CARs before 3-6 mo B-cell aplasia, observed in all responding pts, managed with IVIg replacement therapy The highest manufacture failure rate was observed in patients less than Comment three years of age.

Datamonitor Healthcare Trialtrove Biomedtracker 7 Pharma intelligence | Pharma intelligence | Pharma intelligence | JCAR015 for Acute Lymphocytic Leukemia (ALL)

Phase I – Adults (MSKCC) Change to BMT LOA: 0%

Implications of Minimal Residual Disease Negative Complete Remission (MRD-CR) and Allogeneic Stem Cell Transplant on Safety and Clinical Outcome of CD19-Targeted 19-28z CAR Modified T Cells in Adult Patients with Relapsed, Refractory B-Cell ALL (Abstract #682)

Primary JCAR015 Disease r/r Adult CD19+ B-cell ALL Trial ID NCT01044069 Drug Sponsor Memorial Sloan-Kettering /Juno Lymphodepletion (Cyclophosphoshamide +/- Fludarabine) d-2 Treatment before CTL019 infusion (1 or 3 x 108 T cells/kg) 45 pts; 37/45 overall CR (82%); overall MRD- CR 30/36 (83%); median time to CR = 21 d 13/37 (35%) pts proceeded to allo HSCT after CT Results 18 pts relapsed during follow-up Overall median OS = 8.0; CR pts mOS = 10.6 mo; MRD- CR mOS not reached; MRD+ mOS = 6 mo Severe CRS = 24%; Grade 3/4 neurotoxicity = 28%; Grade 5 = 6% Did adding fludarabine to the lymphodepletion regimen improve CAR-T cell Comment expansion and persistence?

CTL119 for CD19+ Acute Lymphocytic Leukemia (ALL)

Efficacy and Safety of Humanized Chimeric Antigen Receptor (CAR)-Modified T Cells Targeting CD19 in Children with Relapsed/ Refractory ALL (Abstract #683)

Primary CTL119 Disease r/r Pediatric CD19+ ALL Trial ID NCT02374333 Drug Sponsor University of Pennsylvania - Abramson/Novartis Retreatment with CTL119 in relapsed pts previously treated w/ CD19 CAR-T Treatment cells that had partial or no response 6 pts; CRS and neurotoxicity observed – no Grade 4 CRS nor encephalopathy Chronic B cell aplasia required IVIg replacement Results Early B cell recovery (< 6 mo) associated w/ higher risk of relapse Humanized CTL119 induced remissions (50% CR and 83% relapse) The patient population is too small to make conclusions about the benefits Comment of reinfusion/retreatment.

Datamonitor Healthcare Trialtrove Biomedtracker 8 Pharma intelligence | Pharma intelligence | Pharma intelligence | KTE-C19 for Acute Lymphocytic Leukemia (ALL)

Safety and Response of Incorporating CD19 Chimeric Antigen Receptor T Cell Therapy in Typical Salvage Regimens for Children and Young Adults with Acute Lymphoblastic Leukemia (Abstract #684)

Relapsed, Primary KTE-C19 Disease Pediatric/Adolescent, High Trial ID NCT01593696 Drug Risk, CD19+ ALL Sponsor NCI Lymphodepletion (Flu/Cy, FLAG or ifosfamide/etoposide) d-7 to d-2 before Treatment KTE-C19 infusion (MTD = 1 x 106 T cells/kg) 46 pts; CRS/neurotoxicities minimized by grade-driven anti-cytokine therapy 60% overall CR (100% CR MRD-, 84% CR low burden and Results 40% CR high burden); 4% Grade 4 CRS; 40% overall OS Intensifying preparative regimen does not improve outcome Comment Persistence of expanded CAR-T cells is still a problem.

KTE-C19 for Indolent Non-Hodgkin's Lymphoma - NHL

Phase I/II – ZUMA-1 (DLBCL/PMBCL/TFL) Change to BMT LOA: 0%

Phase 1 Clinical Results of the ZUMA-1 (KTE-C19-101) Study: A Phase 1-2 Multi-Center Study Evaluating the Safety and Efficacy of Anti-CD19 CAR T Cells (KTE-C19) in Subjects with Refractory Aggressive Non-Hodgkin Lymphoma (NHL) (Abstract #3991)

Primary Refractory, Aggressive, KTE-C19 Disease Trial ID NCT02348216 Drug Adult CD19+ NHL Sponsor Kite Treatment Flu/Cy lymphodepletion before CTE-C19 infusion (1-2 x 106 T cells/kg) 7 pts; ORR 71% and CR 57% Successful manufacture for all leukapheresed pts Results CRS and neurotoxicity generally reversible Pivotal phase II portion currently enrolling The patient population is too small to make conclusions about the benefits Comment of CD19 CAR-T cell therapy.

Datamonitor Healthcare Trialtrove Biomedtracker 9 Pharma intelligence | Pharma intelligence | Pharma intelligence | CAR-T Cell Therapy Trials in Hematological Malignancies

Shown below are three Trialtrove charts that showcase the breadth of CAR-T cell therapies in terms of trial numbers for primary drugs, disease types and trial phase as of December 2015. CAR-T cell therapies with trial results presented at ASH 2015 are highlighted in yellow.

Primary Drugs CD19-specific T cells 22 tisagenlecleucel-t 14 KTE-C19 CAR 8 JCAR-015 6 CD19-CAR-specific/truncated… 3 JCAR-014 3 JCAR-017 3 Anti-CD19-CAR 2 autologous CAR.CD30 EBV… 2 CAR-T CD19, Cellular Biomedicine… 2 CAR-T CD30, Cellular Biomedicine… 2 ROR1R-CAR-T Cells 2 3rd generation CART cells 1 allogeneic CD19.CAR central… 1 anticancer gene therapy, Takara Bio 1 anticancer therapy, Juno Therapeutics 1 autologous CAR T-cell therapy, Celdara 1 autologous CAR-Kappa CTL 1 bb-2121 1 CAR-BCMA 1 CAR-T CD20, Cellular Biomedicine… 1 CART-33 1 CD19.CAR-CD28Z T cells 1 CD19/4-1BBL armored CAR T cell… 1 chimeric antigen receptor T cell… 1 chimeric antigen receptor T-cell… 1 huCART-19 T cells, Novartis 1 JCAR-018 1 RNA anti-CD19 CAR T cells 1 UCART-19 1 Number of Clinical Trials [Source: Citeline Inc.]

Datamonitor Healthcare Trialtrove Biomedtracker 10 Pharma intelligence | Pharma intelligence | Pharma intelligence | Advancements in PD-1 Development

In the last two years, programmed death receptor-1 (PD-1) – targeted monoclonal antibodies (MAbs) Opdivo (nivolumab; Bristol-Myers Squibb) and Keytruda (pembrolizumab; Merck & Co) have begun to transform treatment paradigms in non-small cell lung cancer and malignant melanoma, and further progress is expected with other drugs targeting PD-1 (and its ligand, PD- L1) in other solid tumors such as renal cell cancer and bladder cancer. In contrast, the number of clinical studies and data generated in hematologic malignancies has so far been lacking.

At ASH 2015, there was strong evidence that this may now be changing and that in the not too distant future PD-1 blockade might be an approved and valuable treatment strategy in a number of hematologic cancers. Oral abstracts at ASH showcased exciting data for Opdivo and Keytruda in Hodgkin’s lymphoma (HL), chronic lymphocytic leukemia (CLL), and multiple myeloma (MM). An overview of the PD-1/PD-L1 development landscape as of December 2015 is captured in the charts below.

Datamonitor Healthcare Trialtrove Biomedtracker 11 Pharma intelligence | Pharma intelligence | Pharma intelligence | Opdivo for Hodgkin's Lymphoma

Phase I - Dose Escalation (CheckMate-039) Change to BMT LOA: +2%

Keytruda for Hodgkin's Lymphoma

Phase I - KEYNOTE-013 (MDS, SMM, HL, NHL) Change to BMT LOA: 0%

Updated data reaffirm clinical potential of PD-1 inhibitors in relapsed/refractory Hodgkin’s lymphoma

In back to back presentations on Monday at ASH, updated Phase I data were presented that reaffirm the clinical potential of PD-1 inhibitors Opdivo (Abstract #583) and Keytruda (Abstract #584) in relapsed/refractory classical Hodgkin’s lymphoma. It has been shown previously that PD-L1 is highly expressed in classical HL, which suggests targeting PD-1/PD-L1 is a viable therapeutic strategy. The data presented at ASH suggest that PD-1 inhibition could be used as a long-term therapy option in patients who have progressed on standard therapies, including Seattle Genetics’ anti-CD30 antibody drug conjugate, Adcetris (brentuximab vedotin). Overall response rates (ORRs) were high in both Opdivo- and Keytruda-treated patients, and responses were shown to be durable. These data strongly suggest PD-1 inhibition will be an approved and recommended treatment strategy in r/r HL that will emerge in the next few years. It is too early to tell whether one of these drugs is more effective than the other. Bristol-Myers Squibb and Merck & Co. have now advanced development of these drugs into Phase II studies.

Dr. Stephen Ansell presented clinical outcomes from extended follow-up of the Phase I CA209- 039 study of Opdivo in r/r classical HL. The data presented were from 23 patients who had received a median of 5 prior therapies (78% has previously received Adcetris). The ORR was 87%, and 22% of patients achieved a complete response (CR). Responses were shown to be durable, and at a median follow up of 101 weeks the median duration of response (DOR) had not been reached. Median progression-free survival (PFS) was also not reached, and the overall survival (OS) rate at 18 months was 83%. Three patients remain on treatment and are progression-free, while 13 have stopped therapy and are still progression-free. Dr. Ansell drew particular attention to one patient who had come off treatment and progressed at a later date and was then re-treated with Opdivo. Six weeks after being re-challenged with Opdivo, this patient responded again. When asked about re-treatment, Dr. Ansell said that the investigators had not yet established the optimum time to initiate re-treatment, but his view was that it is worth attempting to re-treat regardless of when patients progress. Future results releases from this study and data from an ongoing Phase II confirmatory study (CHECKMATE 205, ClinicalTrials.gov identifier: NCT02181738) will be followed closely to establish whether these positive re-treatment data can be replicated in a larger sample size.

Dr. Philippe Armand reported an update on the Phase I KEYNOTE-013 study of Keytruda in patients with r/r classical HL who had previously failed Adcetris therapy. Of the 31 patients treated, 55% had received five or more lines of therapy, and all patients had received Adcetris.

Datamonitor Healthcare Trialtrove Biomedtracker 12 Pharma intelligence | Pharma intelligence | Pharma intelligence | The ORR in all patients was 65% with best response of CR in 16% of patients. Efficacy seemed to be higher in the transplant failure group compared to the transplant ineligible/refused group (ORR 73% versus 44%, respectively). As with the Opdivo study (see above), responses were shown to be durable (71% of patients DOR of ≥24 weeks, PFS at 24 weeks 69%). The investigators showed the results of an exploratory analysis, which suggest that Keytruda induces increases in T-cell and natural killer cell populations, and upregulates T-cell and IFN- gamma signalling pathways. The rate of Grade 3 or above adverse events was fairly high (68%), but this was deemed to be normal in such a heavily pre-treated population. One potential issue that was raised is how to sequence Keytruda with allogeneic stem cell transplantation (SCT). Dr Armand showed that toxicity is markedly higher in patients who receive allo-SCT after completing Keytruda therapy, and that this could complicate decisions regarding whether to perform allo-SCT. However, Dr. Armand said that it is “reasonable to consider holding off (allo- SCT) in patients who are responding well (to Keytruda)”. It is likely that the investigators will look for further evidence of this trend in higher patient numbers in the ongoing KEYNOTE-087 Phase II study (ClinicalTrials.gov, identifier: NCT02453594), which was initiated in June 2015.

Datamonitor Healthcare Trialtrove Biomedtracker 13 Pharma intelligence | Pharma intelligence | Pharma intelligence | Keytruda for Chronic Lymphocytic Leukemia (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

Phase II - MC1485 Change to BMT LOA: 0%

First data for PD-1 blockade in CLL highlights potential niche role for Richter’s transformation therapy

On Monday at ASH, Dr. Wei Ding reported the first data for a PD-1 inhibitor in CLL. These data demonstrate preliminary efficacy for Merck & Co.’s PD-1 inhibitor Keytruda in r/r CLL. The CLL treatment landscape has just entered a period of rapid evolution, with a number of new therapies like the Bruton’s kinase inhibitor Imbruvica (ibrutinib; AbbVie/Johnson & Johnson) and current pipeline candidate venetoclax (AbbVie/Roche) likely to become important components of regimens for both newly-diagnosed and r/r patients. This poses a key question—where could a PD-1 inhibitor fit into the treatment algorithm? The early efficacy report from this Phase II study implies Keytruda could become a valuable treatment option in the future for Richter’s transformation (RS) patients. RS occurs in about 5-10% of all CLL patients, and is associated with poor prognosis and extensive resistance to currently-approved therapies.

In the Phase II study, 20 r/r patients with a median number of three prior therapies have been treated so far. Of these patients, 35% (7/20) had RS, and 55% overall had high-risk cytogenetic status (including chromosome 17p deletion). Out of the 14 evaluable patients, the ORR was 21% which included a CR in one patient. All responders were RS patients. A further three RS patients had stable disease, with disease progression occurring in one RS patient. Five of the seven patients with RS and with response or SD on Keytruda therapy had previously experienced failure of Imbruvica therapy. Clinical response is ongoing in the three responders. Interestingly, one patient who progressed after an initial outcome of stable disease was successfully re-challenged with Imbruvica after Keytruda therapy and now has stable disease again. Dr. Ding said that the observed toxicities were expected and manageable, and that the two deaths on study were attributable to CLL and not to Keytruda. It is important to note that the population of RS patients in this study was very small, but these results are still exciting, and validate further development of Keytruda in RS CLL.

Datamonitor Healthcare Trialtrove Biomedtracker 14 Pharma intelligence | Pharma intelligence | Pharma intelligence | Keytruda for Multiple Myeloma (MM)

Phase I - KEYNOTE-023 (w/Lenalidomide and Dexamethasone) Change to BMT LOA: 0%

KEYNOTE-023 provides proof of concept for PD-1 blockade in multiple myeloma

Updated data from the KEYNOTE-023 Phase II trial demonstrate promising efficacy of the novel triplet regimen of Keytruda plus Revlimid (lenalidomide; Celgene) and dexamethasone for r/r MM. The results can be interpreted as a proof of concept that modification of the immune response by PD-1 blockade can provide clinical benefit to MM patients. With three new therapies recently approved in the space of one month, The MM market is becoming increasingly crowded, and questions have been raised at ASH about where new therapies will fit into the treatment algorithm and in what logical ways different combinations of drugs can be applied to maximize clinical benefit (see below section on TOURMALINE-MM1 pivotal trial results). It is still too early to determine how this novel Keytruda regimen could be integrated among other recommended regimens. Merck & Co. has recently advanced this combination regimen into a Phase III pivotal trial in newly-diagnosed MM patients (versus Revlimid and dexamethasone comparator, ClinicalTrials.gov, identifier: NCT02579863) and is also investigating the combination of Keytruda, Pomalyst (pomalidomide; Celgene), and dexamethasone in r/r MM patients in another Phase III study (ClinicalTrials.gov identifier: NCT02576977).

Dr. Jesus San Miguel presented updated data for the first 17 patients in the dose determination and dose confirmation stages of the KEYNOTE-023 trial. The wider trial (including dose expansion, total 50 patients) has enrolled heavily pre-treated patients (median four prior therapies), a high proportion of who are refractory to Revlimid and Velcade (bortezomib; Takeda/Johnson & Johnson) (96% patients refractory to each). The ORR in the 17 patients was very promising at 76%, and in nine patients who were Revlimid refractory the ORR was also considered to be high at 56%. Disease control rates (DCRs) were 88% in all patients and 78% in the Revlimid-refractory subgroup. Importantly, the responses were shown to be durable (median DOR of 9.7 months at median 296 day follow-up). Dr. San Miguel also showcased an impressive case of a patient who had not responded to eight prior lines of therapy including three Revlimid regimens (triple refactory), and then had a very good partial response (possibly CR) to the Keytruda regimen. In another case study, a patient with extra-medullary disease (commonly a fatal progression of MM) achieved a suspected CR after failing three prior lines of therapy (Revlimid double-refractory). The maximum tolerated dose was determined to be 200mg Keytruda with 25mg Revlimid and 40mg dexamethasone. In the wider study (50 patients), 46% of patients have experienced Grade 3/4 toxicities. These were determined to be consistent with the known adverse event profile of Keytruda. There were few immune-related toxicities, and patients who suffered these did not require dose modification or discontinuation of treatment.

Datamonitor Healthcare Trialtrove Biomedtracker 15 Pharma intelligence | Pharma intelligence | Pharma intelligence | Other Key Immunotherapy Data

Numerous other presentations for immunotherapies with alternative MOAs than those showcased above were presented at ASH 2015. With the rapid proliferation of MM therapies in recent months, perhaps one of the most interesting topics was the dynamic between the two newly-approved antibody therapies, Darzalex (daratumumab; Genmab; Johnson & Johnson) and Empliciti (elotuzumab; Bristol-Myers Squibb).

Darzalex for Multiple Myeloma (MM)

Phase I/II - Monotherapy (501), Phase II - SIRIUS (Double Refractory) Change to BMT LOA: 0%

“Hypothesis generating” data for anti-CD38 MAb Darzalex in heavily pre-treated multiple myeloma (Abstract #29).

On Saturday at ASH, Dr. Saad Usmain presented a combined analysis of the SIRIUS and GEN501 studies that showed promising efficacy of Darzalex monotherapy in heavily pre-treated MM patients. The median OS of 19.9 months (in all patients in the combined analysis) represents a large improvement over treatments that are currently indicated in such heavily pre-treated patients (Pomalyst plus dexamethasone median OS of 12.4 months in relapsed patients who received at least two prior lines of therapy), although this comparison has not been made directly in a clinical trial. No new safety signals associated with Darzalex were identified. Of particular note, Darzalex monotherapy produced an OS benefit in patients who are deemed to be minimal responders or have stable disease (median OS 17.5 months), as well as in patients who responded to treatment (median OS not reached). Dr Usmain described this as “hypothesis generating”, and remarked that the immune-mediated and immunomodulatory mechanisms of Darzalex might be contributing to the survival benefits observed in these patients. It will be interesting to see if similar data emerge from studies of Darzalex’s competitor immunotherapy, Empliciti. However, at present this remarkable finding might serve to promote uptake of Darzalex ahead of Empliciti in heavily pre-treated patients, which is even more significant being as both drugs have only been recently approved.

Datamonitor Healthcare Trialtrove Biomedtracker 16 Pharma intelligence | Pharma intelligence | Pharma intelligence | Combined analysis of the SIRIUS and GEN501 studies of Darzalex monotherapy in heavily pre- treated MM

Treatment description Darzalex Monotherapy (16mg/kg, once weekly weeks 1-3, biweekly weeks 4-5, then monthly) Number of patients 148 Median number prior therapies (% >3 lines) 5 (76%) mDOR 7.6 months PFS rate 12 months 50% ORR 31% PFS in responders NR PFS in minimal responders/stable disease 3.2 months PFS in non-responders 0.9 months Median OS (combined analysis) 19.9 months 1 year OS rate (combined analysis) 69% OS in responders NR OS in minimal responders/stable disease 17.5 months OS in non-responders 3.7 months

Empliciti for Multiple Myeloma (MM)

Phase III – ELOQUENT-2 Change to BMT LOA: 0%

ELOQUENT-2 update shows marginal OS advantage with Emplicity/Revlimid doublet in r/r MM

An update on the ELOQUENT-2 study showed that the addition of Empliciti to Revlimid and dexamethasone might improve OS in r/r MM patients. Dr. Meletios Dimopoulos presented data that showed OS of r/r MM patients treated with the combination of the anti-SLAM7 MAb Empliciti with Revlimid and dexamethasone may be higher than OS of patients who received Revlimid and dexamethasone. The OS benefit appears to be marginal (43.7 months versus 39.6 months), and was described as a “strong trend”. This will be viewed quite negatively when considering this patient population has not been that heavily pre-treated (median two prior therapies), and that addition of an expensive MAb to the well-established regimen of Revlimid plus dexamethasone does not seem to be providing much additional clinical benefit. Furthermore, statistical significance of the OS data has not yet been reached. As a result, Empliciti is likely to struggle to compete in earlier lines of therapy, especially when the market has recently been flooded with a number of new therapies (including rival MAb Darzalex). Dr Dimopoulos closed his presentation by drawing attention to the diversity of the ongoing clinical program of Empliciti in MM, which includes a Phase II study of Empliciti monotherapy in smoldering myeloma (ClinicalTrials.gov identifier: NCT01441973).

Datamonitor Healthcare Trialtrove Biomedtracker 17 Pharma intelligence | Pharma intelligence | Pharma intelligence | ELOQUENT-2 updated data with OS

Treatment description Empliciti (10mg/kg) + Revlimid + Revlimid + Dexamethasone Dexamethasone Number of patients 318 317 Median number prior therapies 2 2 PFS rate 1/2/3 years 68%/41%/26% 57%/27%/18% Median PFS 19.4 months 14.9 months Reduction in risk of death or 27% (HR 0.73; P=0.0014) N/A disease progression Time to next treatment 33 months 21 months ORR 79% 66% Median OS 43.7 months (HR 0.77; 39.6 months P=0.0257)

Datamonitor Healthcare Trialtrove Biomedtracker 18 Pharma intelligence | Pharma intelligence | Pharma intelligence | Other Drugs/Therapies of Interest

Zydelig for Chronic Lymphocytic Leukemia (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

Phase II - w/Ofatumumab (Dana-Farber) Change to BMT LOA: 0%

Severe liver toxicity will likely preclude use of Zydelig in the CLL first-line setting

In Monday’s front-line CLL therapy session at ASH, Dr. Benjamin Lampson discussed Phase II data that demonstrate Zydelig (idelalisib; Gilead) treatment results in “severe and frequent” immune-mediated hepatotoxicity in previously-untreated patients. The serious nature of this finding decreases the likelihood that Zydelig will join Imbruvica in the first-line CLL treatment setting in the future. Despite this, Gilead is going ahead with a Phase III first-line CLL program investigating Zydelig in combinations with other CLL drugs.

The probable cause of the hepatotoxicity observed was said to be an adaptive immune response that is specific to previously-untreated patients. Zydelig already carries a black box warning for hepatotoxicity in its prescribing information for its current indication for treatment of relapsed/refractory and high-risk CLL, but the frequency and timing of adverse events in the supporting studies (occurring in 14% of patients) were not linked to an immune response.

In this Phase II study, patients were treated with Zydelig monotherapy (150mg twice daily) followed by a period of Zydelig-Arzerra combination therapy, and then a switch back to Zydelig monotherapy. Dr. Lampson said that the time of onset of transaminitis in this Phase II study was indicative of an adaptive immune response. The peak of transaminitis incidence was at week four, with 34% of the 24 patients experiencing Grade 3 or 4 transaminitis that is indicative of impaired liver function. The majority of these patients (80%) received systemic corticosteroids to combat this adverse event. In 12 patients whose therapy was stopped due to transaminitis, rechallenging with Zydelig at a later date resulted in rapid recurrence of transaminitis in half of these patients. Immunohistochemistry assays performed in two patients who experienced Grade 4 transaminitis showed increased levels of cytotoxic T cell levels in the liver parenchyma compared to normal CLL controls. Furthermore, a significant proportion of patients also had a decrease in percentage of regulatory T cells in the peripheral blood over time. Dr. Lampson stressed that these findings reinforced the hypothesis that Zydelig toxicity in first-line CLL is likely immune-mediated. Efficacy data were not presented.

Datamonitor Healthcare Trialtrove Biomedtracker 19 Pharma intelligence | Pharma intelligence | Pharma intelligence | Acalabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

Phase I/II – ACE-CL-001 Change to BMT LOA: +2%

Second generation BTK inhibitor ACP-196 will go head to head with Imbruvica

In a presentation of early-Phase data, Acerta Pharma shone the spotlight on the advancement of its second generation BTK inhibitor ACP-196 into a Phase III trial testing it head to head against AbbVie’s first-in-class BTK inhibitor Imbruvica in high risk CLL. Dr. John Byrd presented pre-clinical data that prove ACP-196 has superior pharmacokinetics to Imbruvica in vitro and in humans with CLL. The very early clinical data here were also promising, and clearly gave Acerta the confidence to challenge Imbruvica in a pivotal trial. Challenging an existing drug that is considered a standard of care (as Imbruvica is in high-risk CLL) is something that is not seen enough in oncology development, and the first results of the Phase III study (ClinicalTrials.gov identifier: NCT02477696, currently recruiting patients) will be eagerly anticipated.

Dr. Byrd showed pharmacokinetic data that revealed complete BTK inhibition is possible with a twice daily oral dose of 100mg ACP-196. In 61 r/r CLL patients (the majority of who had high- risk genetic markers), twice daily ACP-196 (dose escalation) was well tolerated. There were no documented incidences of atrial fibrillation or major bleeding (any grades). There was one case of fatal pneumonia, though this was said to be not attributable to ACP-196. The ORR rate was 95%, and in the chromosome 17p deletion subgroup the ORR was 100%. Most patients who responded to therapy experienced dramatic improvements in spleen lymphadenopathy at a median of 14.3 months follow up.

Datamonitor Healthcare Trialtrove Biomedtracker 20 Pharma intelligence | Pharma intelligence | Pharma intelligence | Pivotal Trials

Midostaurin for Acute Myelogenous Leukemia (AML)

Phase III – RATIFY (FLT3+) Change to BMT LOA: +3%

Midostaurin represents a new standard of care for some AML patients, 30 years after the last breakthrough

The highlight of the plenary session at ASH 2015 was the reporting of pivotal data from the RATIFY trial of Novartis’s multi-kinase inhibitor midostaurin in newly-diagnosed FLT3 mutated (FLT3m) acute myeloid leukemia (AML) patients <60 years of age. The combination of midostaurin with standard chemotherapy will become a new standard of care for these patients, and marks the first significant change in the pharmacological treatment of AML for 30 years. The next steps will be to ascertain as to whether the drug has a therapeutic role to play in patients >60 years of age and whether it works beyond FLT3m.

The results of the RATIFY study, presented by Dr. Richard Stone of the Dana-Farber Cancer Insititute (Boston, US), demonstrated the addition of midostaurin (50mg) to an existing established chemotherapy regimen led to statistically significant improvements in patients’ OS, event-free survival (EFS), and disease-free survival (DFS) when compared to standard chemotherapy without midostaurin. The OS rate at four years was 51.4% in the midostaurin arm compared to 44.2% in the control arm, with a 23% reduction in risk of death associated with midostaurin therapy (HR 0.77, P=0.0074). For patients who went on to receive allo-SCT, OS was also higher with midostaurin when censored at the time of transplant, and patients treated with midostaurin followed by allo-SCT were found to have enhanced OS (after first CR) compared to patients who received allo-SCT but no prior midostaurin. EFS was 8 months in the midostaurin arm versus 3 months in the control arm (HR 0.79, P=0.0025), and DFS was 26.9 months in the midostaurin arm versus 14.4 months in the comparator arm (HR 0.7, P=0.002). The safety profile of midostaurin plus chemotherapy was deemed to be no different from the profile of chemotherapy alone.

The RATIFY data were widely praised at ASH, and physicians involved in the treatment of AML generally agreed that midostaurin plus chemotherapy will become a new standard of care for this young FLT3m patient subpopulation. Regulatory filings for midostaurin are expected to occur in the first half of 2016.

While the RATIFY data signifies a breakthrough in AML therapy, it is clear that high unmet need will remain post-approval of midostaurin, and that the next steps will be to further evaluate its therapeutic potential in other patient groups. The patient population midostaurin will be indicated in comprises only a small proportion of all patients, as it will be limited by FLT3m status (this mutation occurs in approximately 30% of all AML patients) and age (the median age of AML diagnoses has been estimated to be 68-70, and midostaurin will likely be indicated for patients under 60). Dr. Stone referred to the outcome of RATIFY as a “small win”, and

Datamonitor Healthcare Trialtrove Biomedtracker 21 Pharma intelligence | Pharma intelligence | Pharma intelligence | acknowledged there needs to be a lot more work. He said it would be prudent to test for other mutations that might predict response in older patients, but he does not currently see “big implications” for the treatment of older patients. One important finding Dr Stone did highlight was that the drug was effective in patients with varying allelic burden of FLT3m. He attributed the fact that it works in patients who do not have as high levels of FLT3m to the fact that it is a “dirty drug” that is hitting many other targets other than FLT3m, and that for this reason it should be tested further beyond FLT3 subgroups. If this work is carried out, it could lead to label expansions for midostaurin in the future.

Imbruvica for Chronic Lymphocytic Leukemia (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

Phase III - RESONATE-2 (Elderly) (PCYC-1115) Change to BMT LOA: 0%

RESONATE-2 data demonstrate Imbruvica will transform CLL therapy for elderly patients

Top-line data from the RESONATE-2 trial demonstrate that Imbruvica is extremely effective in first-line treatment of elderly CLL patients. Although OS data are not yet mature, it is already clear that the drug will radically improve treatment outcomes in elderly patients, and patients with poor performance status. Approval of an sNDA for Imbruvica in treatment-naïve CLL which AbbVie submitted in September is almost certain, and this will represent further progress towards the drug becoming the most flexible therapy option in the CLL treatment landscape.

On Monday, December 7, 2015, at ASH, Dr. Alessandra Tedeschi presented top-line data from the Phase III RESONATE-2 study that showed Imbruvica monotherapy (420mg daily) is superior to chlorambucil (0.8mg/kg twice in a 28 day cycle) in elderly (≥65 years old) treatment-naïve CLL patients. Various measures of PFS and ORR were reported, but perhaps what best illustrates how effective Imbruvica is in this patient population is the 18 month PFS rate (independently assessed) of 90% with Imbruvica versus 52% with chlorambucil. Median PFS was superior in the Imbruvica arm (not reached) compared to the chlorambucil arm (18.9 months) (HR 0.16, 95% CI 0.09-0.28, P<0.0001). There was an 84% reduction in risk of death associated with Imbruvica therapy (HR 0.16, 95% CI 0.05-0.56 P=0.001). The ORR (at 8 months) in the Imbruvica arm was 84% versus 31% in the chlorambucil arm. Imbruvica showed a number of other clinical advantages over chlorambucil, including improvements in lymph node burden, spleen enlargement, anemia, and thrombocytopenia. Imbruvica’s safety profile was deemed acceptable, with most frequent AEs of diarrhea, fatigue, cough and nausea. Adverse events leading to discontinuation of treatment were lower with Imbruvica than chlormabucil (9% versus 23%). These data mark a major breakthrough in treatment for elderly CLL patients. Elderly patients often present with comorbidities and disease-related symptoms that contraindicate the use of more aggressive first-line approaches used in younger patients such as FCR (fludarabine, cyclophosphamide and Rituxan). Dr. Tedeschi said that the hematologic improvements observed in the Imbruvica arm were “clinically relevant, as bone marrow failure is common in

Datamonitor Healthcare Trialtrove Biomedtracker 22 Pharma intelligence | Pharma intelligence | Pharma intelligence | these patients”. Younger patients with poor performance status are also likely to benefit from first-line Imbruvica monotherapy. The current standard of care for patients not eligible for more aggressive regimens is chlorambucil monotherapy, which has previously been shown to be active in 51% of patients >65 years of age, with median OS of 64 months (CLL5 study). RESONATE-2 shows that Imbruvica is a dramatic improvement over chlorambucil. It is still too early to say how much of an improvement in OS Imbruvica will confer to these patients, but the Kapplan-Meier plots displayed at ASH suggest it might be a long time before enough events occur to provide median OS.

Imbruvica is fast becoming the most flexible treatment option in CLL. It was initially approved for both treatment of high-risk CLL patients (chromosome 17p deletion) patients (regardless of line of therapy) and treatment of relapsed/refractory CLL. Armed with RESONATE-2 data, it will now be approved for first-line CLL. AbbVie and Johnson & Johnson are continuing to develop the drug in a number of Phase III trials that will likely facilitate further label expansions. Further expansion of the drug’s label will serve to increase the number of patients it can be prescribed to and enhance commercial reward. The table below summarizes the potential future label expansions Imbruvica could be granted in CLL, and the Phase III clinical studies that would support them.

Potential future label expansions for Imbruvica in CLL and supporting clinical studies

Potential Label Study Patients Intervention Interim Data expansion Combination HELIOS 578 Imbruvica + BR ORR = 82.7% w/Treanda and r/r CLL vs. BR Alone Imbruvica + BR vs. Rituxan (BR regimen) 67.8% BR;

Relapsed/Refractory PFS = not reached (r/r) CLL Imbruvica + BR vs. 13.3 months BR sNDA Submitted to FDA November 2015

Combination iLLUMINATE 302 Imbruvica + No data yet reported w/Gazyva Gazyva vs. Chlorambucil + First-Line CLL Gazyva Source: BioMedTracker

Datamonitor Healthcare Trialtrove Biomedtracker 23 Pharma intelligence | Pharma intelligence | Pharma intelligence | Ninlaro for Multiple Myeloma (MM)

Phase III - TOURMALINE-MM1 (w/Len/Dex) Change to BMT LOA: 0%

TOURMALINE MM-1 data demonstrate strong efficacy of Ninlaro-triplet regimen but where will it fit in to multiple myeloma treatment?

Updated data from the TOURMALINE MM-1 pivotal trial of Ninlaro (ixazomib; Takeda) in r/r MM including the final PFS analysis and an interim OS update, were enthusiastically received at ASH 2015. In November, Ninlaro in combination with Revlimid and dexamethasone became the first all-oral triplet regimen to be approved for MM (in r/r patients), based on the results of TOURMALINE MM-1. While being an all-oral regimen is a positive point of differentiation from other triplet regimens currently in use, the question being asked at ASH was where this new regimen will fit into the treatment landscape, which is now extremely competitive and contains a high degree in flexibility of regimen use?

The TOURMALINE-MM1 results, presented by Dr. Philippe Moreau, demonstrated that the Ninlaro (4mg once weekly)/Revlimid/dexamethasone combination represents a valuable new treatment option for both standard- and high-risk r/r MM patients. The final PFS analysis in 722 patients showed a 35% statistically significant improvement in PFS associated with the new triplet regimen as opposed to the Revlimid/dexamethasone doublet plus placebo (20.6 months versus 14.7 months, HR 0.74, 95% CI 0.587-0.939 P=0.012). This benefit was shown to be consistent across all pre-specified patient subgroups, and was not different in patients with high-risk cytogenetics compared to standard-risk patients (high-risk PFS 21.4 months Ninlaro group versus 9.7 months placebo, standard-risk PFS 20.6 months versus 15.6 months). Median OS had not yet been reached in either arm at the time of the pre-specified interim analysis. Dr. Moreau described the triplet therapy as “a very safe one” and stressed that “quality of life was maintained despite addition of a further agent (Ninlaro).” The rate of Grade 3/4 adverse events was marginally higher in the Ninlaro arm, primarily due to increased thrombocytopenia. Rates of discontinuation were similar between arms. Ninlaro treatment was associated with low rates of peripheral neuropathy (a common adverse event with proteasome inhibitor Velcade), and there were no cardiac or renal safety signals.

The key question being asked by physicians and other stakeholders at ASH is where will Ninlaro fit into the treatment of MM, given that there are a number of new treatment options available? In short, there is no straightforward answer, and a consensus might only be reached after the publication of clinical trial results of many further studies of different MM drugs. In the r/r setting, Ninlaro must not only compete with current standard of care proteasome inhibitor Velcade, but it must also compete with the newer intravenous proteasome inhibitor Kyprolis (carfilzomib; Amgen), and brand new MAb therapies Darzalex and Empliciti. Development of all of these drugs in various different combination regimens is ongoing, which complicates decisions regarding choice of which to use in different patient groups and lines of therapy. When asked to describe the ideal patient who might benefit, Dr. Moreau commented that we now have “three new different combination triplet regimens, and we will have to look at all patient subgroups to work out who is benefitting from what.” Initially, Ninlaro is likely to

Datamonitor Healthcare Trialtrove Biomedtracker 24 Pharma intelligence | Pharma intelligence | Pharma intelligence | be used in patients who have already received Velcade, as the strong efficacy data in TOURMALINE-MM1 were achieved in a patient population that was heavily Velcade-exposed (69% prior exposure in each arm).

Takeda is continuing to develop Amgen in three other pivotal trials with the aim of securing future label expansions that will broaden its coverage of the MM patient population and enhance its commercial potential. The TOURMALINE-MM2 study (ClinicalTrials.gov, identifier: NCT01850524) is expected to support a first-line label expansion for the Ninlaro/Revlimid/dexamethasone combination. TOURMALINE-MM3 (ClinicalTrials.gov, identifier: NCT02181413) might facilitate use of Ninlaro as a maintenance monotherapy in patients who receive autologous SCT. TOURMALINE-MM4 (ClinicalTrials.gov, identifier: NCT02312258) could support a future label expansion for Ninlaro’s use as a maintenance monotherapy in patients who respond to induction therapy and do not receive SCT.

Datamonitor Healthcare Trialtrove Biomedtracker 25 Pharma intelligence | Pharma intelligence | Pharma intelligence | First-in-Human in Hematological Malignancies

Drug Description Disease Sponsor Treatment Results ASH ID CAR-BCMA See Synopsis Above LBA-1

WT1-TCR WT1-specific TCR-gene Refractory Takara Dose escalation 5 pts; No SAEs related 97 T cells transduced AML or MDS 2 x 108 – 5 x 109 to therapy T cells Ineligible T cells infused d0 and d28 300 mg modified WT1 + Montanide given SC d2 and d16 ABL001 BCR-ABL inhibitor r/r chronic/ Novartis Dose escalation: BID 30 pts; MTD not 138 accelerated 10-150 mg reached; 3 DLTs; CML 6/11 pts achieved CCyR (resistance/int olerant to TKIs) Gilteritinib FLT3/AXL inhibitor r/r AML Astellas Dose escalation or 169 FLT3 mutant pts 321 randomized in dose treated w/ > 80 mg; expansion cohorts 53 % ORR; 31 wk OS Tazemetostat EZH2 HMT inhibitor r/r B-cell NHL Epizyme Dose escalation 100 21 pts; 9/16 ORR; 473 – 1600 mg BID RP2D = 800 mg BID ACP-196 See Synopsis Above 831

BGB-3111 Selective, oral Bruton’s TKI r/r B-cell NHL BeiGene Dose escalation 39 pts; MTD not 832 or CLL Dose expansion at reached; RP2D (330 mg daily) No DLT; CLL ORR 93% AG-120 Mutant IDH1 inhibitor IDH1 mut + Agios QD and BID dose 87 pts; for 78 pts – 1306 HM* escalation (100 – ORR 35%, CR 15%, 1200 mg daily) DOR 5.6 mo JCAR018 CD22 CAR-T cells r/r CD22+, NCI/Juno Cy/Flu 9 pts – 7 treated; 1324 pediatric ALL lymphodepletion 2 MRD- CR then 3 x 105 – 106 T cells/kg CPI-0610 BET proteins inhibitor r/r HL or NHL Constellation Dose escalation d1- 44 pts; 1491 14 MTD not reached; 6-230 mg QD well tolerated RP6530 Dual PI3K δ/γ inhibitor r/r HM* Rhizen Dose escalation 25 – 26 pts; no DLTs; Dose 1495 800 mg BID escalation ongoing ASTX727 Decitabine + E7727 MDS Astex Dose escalation: 20- 24 pts; cohorts 1-4 no 1683 40 mg D and 40-10 DLTs mg E Cirmtuzumab ROR1 antagonist r/r CLL Univ. of CA, San Dose escalation 15 10 pts; well tolerated 1736 Diego μg – 1 mg/kg ALT-803 IL-15/IL-15Rα-Fc relapsed HM* Altor Escalating IV weekly 16 pts; no DLT; ongoing 1957 superagonist complex doses SC dosing at 6 μg/kg (1-30 μg/kg) x 4 UCART19 Universal CD19 CAR-T cells relapsed, high UCL/ Lymphodepletion, Case study; 2046 – TALEN engineered risk, CD19+, GOSH/ Cellectis 4.5 x 106 T cells/kg Molecular complete pediatric B-cell infusion and remission ALL allogenic transplantation AG-221 Mutant IDH2 inhibitor IDH2 mut + Agios/ Dose escalation 50 – 231 pts; 79/209 ORR; 2509 HM* Celgene 650mg daily; Dose 37/209 CRR; expansion 100mg 6.9 mo DOR AML

Datamonitor Healthcare Trialtrove Biomedtracker 26 Pharma intelligence | Pharma intelligence | Pharma intelligence | Pinometostat DOT1L HMT inhibitor r/r MLL Epizyme Dose escalation 42 pts; 2547 rearranged Dose expansion at 90 MTD not reached; leukemia or mg/m2 or 54 mg/m2 Acceptable safety HM* given continuous IV for 21/28 d TAK-659 SYK inhibitor r/r HL or NHL Takeda Dose escalation 60- 10 pts; 2693 120 mg MTD not reached; PR 3/7 DLBCL pts IMMU-114 Anti-HLA-DR mAb r/r B-cell NHL Immunomedics 200 mg 1-3/wk SC for 17 pts; 2740 or CLL 3 wk of 4 wk cycle. MTD not reached; 4/10 Repeated once w/ ORR elective maintenance ACY-241 HDAC6 inhibitor r/r MM Acetylon ACY-241 180 or 360 1st pt enrolled Jun 2015 3040 mg (cycle 1) + pomalidomide/ dexamethasone (cycle 2) Roneparstat Heparanase inhibitor refractory MM sigma-tau Dose escalation 25 – 16 pts; no DLT; 3246 400 mg QD SC d1-5 expansion at 300 or 400 or d1-10 mg/day 4SCAR123 CD123 CAR – T cells Refractory GIMI Lymphodepletion, 1 pt pilot 3778 AML 1.8 x 106 cells/kg infusion *HM = Hematological Malignancies

Datamonitor Healthcare Trialtrove Biomedtracker 27 Pharma intelligence | Pharma intelligence | Pharma intelligence | Top-Line Results Presented at ASH Supplied by BioMedTracker

BioMedTracker Drug Name Indication Lead Company Partner Event

191522 IMO-8400 Waldenstrom Macroglobulinemia Idera Pharmaceuticals, (WM) / Lymphoplasmacytic Inc. Lymphoma (LPL) - NHL

191587 Ninlaro Multiple Myeloma (MM) Takeda Pharmaceutical Company Ltd

191594 WT1-CTL Multiple Myeloma (MM) Atara Biotherapeutics, Inc. Memorial Sloan-Kettering Cancer Center

191598 JCAR018 Acute Lymphocytic Leukemia (ALL) Juno Therapeutics Inc. Celgene (CELG), Opus

191601 Qinprezo Myelodysplastic Syndrome (MDS) Sunesis Pharmaceuticals, Sumitomo Dainippon Inc. Pharma (4506:JP)

191612 GMI-1271 Venous Thromboembolism (VTE) GlycoMimetics, Inc.

191617 Revlimid Multiple Myeloma (MM) Celgene Corporation

191637 BPX-501 Bone Marrow Transplant and Stem Bellicum Pharmaceuticals, Ariad (ARIA) Cell Transplant Inc.

191641 SD-101 Hematologic Cancer Dynavax Technologies Corporation

191670 Luspatercept Myelodysplastic Syndrome (MDS) Acceleron Pharma, Inc. Celgene (CELG)

191698 Nplate Immune Thrombocytopenic Purpura Amgen, Inc. Kyowa Hakko Kirin (4151:JP), (ITP) Takeda (4502:JP)

191702 TG-1303 Chronic Lymphocytic Leukemia TG Therapeutics, Inc. (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

191703 TG-1303 Diffuse Large B-Cell Lymphoma TG Therapeutics, Inc. (DLBCL) - NHL

191704 TG-1303 Non-Hodgkin's Lymphoma (NHL) TG Therapeutics, Inc.

191705 TGR-1202 Chronic Lymphocytic Leukemia TG Therapeutics, Inc. Rhizen Pharmaceuticals (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

191706 TGR-1202 Non-Hodgkin's Lymphoma (NHL) TG Therapeutics, Inc. Rhizen Pharmaceuticals

191712 Gilteritinib Acute Myelogenous Leukemia (AML) Astellas Pharma, Inc.

191721 Imetelstat Myelodysplastic Syndrome (MDS) Geron Corporation Johnson & Johnson (JNJ)

191730 ABL-001 Chronic Myelogenous Leukemia Novartis AG (CML)

191734 Ublituximab Chronic Lymphocytic Leukemia TG Therapeutics, Inc. Ildong Pharmaceutical, LFB (CLL)/Small Cell Lymphocytic Group Lymphoma (SLL) - NHL

191744 ABL-001 Acute Lymphocytic Leukemia (ALL) Novartis AG

191775 Pidilizumab Multiple Myeloma (MM) Medivation, Inc. CureTech

192010 Selinexor Acute Myelogenous Leukemia (AML) Karyopharm Therapeutics

191572 LentiGlobin Sickle Cell Anemia bluebird bio

191583 CB-839 Hematologic Cancer Calithera Biosciences, Inc.

Datamonitor Healthcare Trialtrove Biomedtracker 28 Pharma intelligence | Pharma intelligence | Pharma intelligence | 191615 MOR208 Chronic Lymphocytic Leukemia MorphoSys AG Xencor (XNCR) (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

191623 Adynovate Hemophilia A Baxalta Incorporated Nektar (NKTR)

191656 Imbruvica Multiple Myeloma (MM) AbbVie Inc. Johnson & Johnson (JNJ), Royalty Pharma

191659 TGR-1202 Chronic Lymphocytic Leukemia TG Therapeutics, Inc. Rhizen Pharmaceuticals (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

191689 Folotyn Cutaneous T-Cell Lymphoma (CTCL) - Spectrum Clinigen Group (CLIN:L), NHL Pharmaceuticals, Inc. Mundipharma

191691 Alisertib Peripheral T-Cell Lymphoma (PTCL) - Takeda Pharmaceutical NHL Company Ltd

191693 Midostaurin Acute Myelogenous Leukemia (AML) Novartis AG

191743 Venetoclax Acute Myelogenous Leukemia (AML) AbbVie Inc. Roche (RHHBF)

191750 Oprozomib Multiple Myeloma (MM) Amgen, Inc. Ono (4528:JP)

191762 Midostaurin Acute Myelogenous Leukemia (AML) Novartis AG

191524 PRS-080 Anemia Pieris AG

191530 KTE-C19 Indolent Non-Hodgkin's Lymphoma - Kite Pharma, Inc. NHL

191545 Keytruda Multiple Myeloma (MM) Merck & Co., Inc.

191585 GBT440 Sickle Cell Anemia Global Blood Therapeutics Inc.

191657 IMMU-114 Non-Hodgkin's Lymphoma (NHL) Immunomedics, Inc.

191660 IMMU-114 Chronic Lymphocytic Leukemia Immunomedics, Inc. (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

191667 Imbruvica Mantle Cell Lymphoma - NHL AbbVie Inc. Johnson & Johnson (JNJ), Royalty Pharma

191747 ARRY-520 Multiple Myeloma (MM) Array BioPharma, Inc.

191773 NPI-0052 Multiple Myeloma (MM) Triphase Research & Celgene (CELG) Development I Corp.

191782 Linsitinib Multiple Myeloma (MM) Astellas Pharma, Inc. Multiple Myeloma Research Foundation

191787 Sotatercept Multiple Myeloma (MM) Acceleron Pharma, Inc. Celgene (CELG)

191789 Pinometostat Acute Myelogenous Leukemia (AML) Epizyme, Inc. Celgene (CELG)

191796 Keytruda Multiple Myeloma (MM) Merck & Co., Inc.

191804 Imbruvica Indolent Non-Hodgkin's Lymphoma - AbbVie Inc. Johnson & Johnson NHL (JNJ), Royalty Pharma

191808 DC Vaccines Acute Myelogenous Leukemia (AML) MediGene AG

191814 DC Vaccines Acute Myelogenous Leukemia (AML) MediGene AG

191816 Jakafi Myelofibrosis (MF) Incyte Corporation Novartis (NVS)

191822 Biosimilar Pegfilgrastim Neutropenia / Leukopenia Novartis AG (Sandoz)

191828 Neukoplast Acute Myelogenous Leukemia (AML) NantKwest, Inc. Sorrento Therapeutics (SRNE)

Datamonitor Healthcare Trialtrove Biomedtracker 29 Pharma intelligence | Pharma intelligence | Pharma intelligence | 191833 Velcade Diffuse Large B-Cell Lymphoma Takeda Pharmaceutical Johnson & Johnson (DLBCL) - NHL Company Ltd (JNJ)

191902 BGB-3111 Hematologic Cancer BeiGene, Co., Ltd.

191994 KTE-C19 Diffuse Large B-Cell Lymphoma Kite Pharma, Inc. (DLBCL) - NHL

191995 Selinexor Acute Myelogenous Leukemia (AML) Karyopharm Therapeutics

192014 Venetoclax Chronic Lymphocytic Leukemia AbbVie Inc. Roche (RHHBF) (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

192467 AGS67E Hematologic Cancer Astellas Pharma, Inc. Seattle Genetics (SGEN)

192748 Keytruda Chronic Lymphocytic Leukemia Merck & Co., Inc. (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

191881 Zydelig Chronic Lymphocytic Leukemia Gilead Sciences, Inc. (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

192008 NI-0501 Inflammatory Disorders NovImmune SA

Datamonitor Healthcare Trialtrove Biomedtracker 30 Pharma intelligence | Pharma intelligence | Pharma intelligence | Additional Results Presented at ASH Supplied by BioMedTracker

BioMedTracker Drug Name Indication Lead Company Partner Event

191533 Pacritinib Myelofibrosis (MF) CTI BioPharma Baxalta (BXLT), S*BIO Corporation

191547 LentiGlobin Anemia bluebird bio

191599 Denintuzumab Acute Lymphocytic Leukemia (ALL) Seattle Genetics, Inc. Mafodotin

191605 Empliciti Multiple Myeloma (MM) Bristol-Myers Squibb AbbVie (ABBV) Company

191609 GMI-1271 Acute Myelogenous Leukemia (AML) GlycoMimetics, Inc.

191624 MOR208 Diffuse Large B-Cell Lymphoma MorphoSys AG Xencor (XNCR) (DLBCL) - NHL

191680 Jakafi Myelofibrosis (MF) Incyte Corporation Novartis (NVS)

191699 Iclusig Chronic Myelogenous Leukemia ARIAD Pharmaceuticals, Angelini, Endo (ENDP), Gen Ilac, (CML) Inc. Medison, Otsuka (4768:JP), PDL BioPharma (PDLI), Specialised Therapeutics Australia

191713 Birinapant Myelodysplastic Syndrome (MDS) TetraLogic Pharmaceuticals

191728 Tasigna Chronic Myelogenous Leukemia Novartis AG (CML)

191731 Tipifarnib (Oncology) Acute Myelogenous Leukemia (AML) Kura Oncology, Inc. Johnson & Johnson (JNJ)

191786 Imetelstat Essential Thrombocythemia (ET) Geron Corporation Johnson & Johnson (JNJ)

191843 Adcetris Anaplastic Large Cell Lymphoma Seattle Genetics, Inc. Takeda (4502:JP) (ALCL) - NHL

191845 Adcetris Peripheral T-Cell Lymphoma (PTCL) - Seattle Genetics, Inc. Takeda (4502:JP) NHL

191873 Reolysin Multiple Myeloma (MM) Oncolytics Biotech Inc.

192165 PRM-151 Myelofibrosis (MF) Promedior, Inc. Bristol-Myers Squibb (BMY)

191523 Darzalex Multiple Myeloma (MM) Johnson & Johnson Genmab (GEN:DC)

191529 Imbruvica Chronic Lymphocytic Leukemia AbbVie Inc. Johnson & Johnson (JNJ), (CLL)/Small Cell Lymphocytic Royalty Pharma Lymphoma (SLL) - NHL

191532 Venetoclax Chronic Lymphocytic Leukemia AbbVie Inc. Roche (RHHBF) (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

191541 Gilteritinib Acute Myelogenous Leukemia (AML) Astellas Pharma, Inc.

191566 LentiGlobin Anemia bluebird bio

191573 LentiGlobin Sickle Cell Anemia bluebird bio

191578 CMV-CTL Cytomegalovirus (CMV) Infection Atara Biotherapeutics, Inc. Memorial Sloan-Kettering (Antiviral) Cancer Center, QIMR Berghofer

191579 JCAR014 Hematologic Cancer Juno Therapeutics Inc. Celgene (CELG)

191586 Denintuzumab Non-Hodgkin's Lymphoma (NHL) Seattle Genetics, Inc. Mafodotin

Datamonitor Healthcare Trialtrove Biomedtracker 31 Pharma intelligence | Pharma intelligence | Pharma intelligence | 191590 CB-839 Hematologic Cancer Calithera Biosciences, Inc.

191610 Adcetris Hodgkin's Lymphoma Seattle Genetics, Inc. Takeda (4502:JP)

191614 SGN-CD33A Acute Myelogenous Leukemia (AML) Seattle Genetics, Inc.

191621 CUDC-907 Diffuse Large B-Cell Lymphoma Curis, Inc. (DLBCL) - NHL

191622 Beleodaq Peripheral T-Cell Lymphoma (PTCL) - Spectrum Onxeo (EPA:ONXEO) NHL Pharmaceuticals, Inc.

191625 Adcetris Hodgkin's Lymphoma Seattle Genetics, Inc. Takeda (4502:JP)

191647 AG-120 Acute Myelogenous Leukemia (AML) Agios Pharmaceuticals, Celgene (CELG) Inc.

191673 AG-221 Acute Myelogenous Leukemia (AML) Celgene Corporation Agios (AGIO)

191674 MOR202 Multiple Myeloma (MM) MorphoSys AG

191679 CTL019 Diffuse Large B-Cell Lymphoma Novartis AG Regenerex, UPenn (DLBCL) - NHL

191684 Tosedostat Acute Myelogenous Leukemia (AML) CTI BioPharma Vernalis (VER:LN) Corporation

191707 Birinapant Myelodysplastic Syndrome (MDS) TetraLogic Pharmaceuticals

191709 NutreStore Sickle Cell Anemia Emmaus Medical, Inc.

191737 Soliris Hemolytic Uremic Syndrome (HUS) Alexion Pharmaceuticals, DRI Capital, Lonza (LZAGY) Inc.

191751 Venetoclax Non-Hodgkin's Lymphoma (NHL) AbbVie Inc. Roche (RHHBF)

191758 ALN-CC5 Paroxysmal Nocturnal Alnylam Pharmaceuticals, Hemoglobinuria (PNH) Inc.

191759 Kyprolis Multiple Myeloma (MM) Amgen, Inc. Dr. Reddy's (RDY), Ligand (LGND), Ono (4528:JP)

191761 Vyxeos Acute Myelogenous Leukemia (AML) Celator Pharmaceuticals, Inc.

191763 rIX-FP Hemophilia B CSL Limited

191768 Pinometostat Acute Myelogenous Leukemia (AML) Epizyme, Inc. Celgene (CELG)

191812 Pomalyst Multiple Myeloma (MM) Celgene Corporation

191851 Jakafi Polycythemia Vera (PV) Incyte Corporation Novartis (NVS)

191852 Jakafi Myelofibrosis (MF) Incyte Corporation Novartis (NVS)

191914 Soliris Hemolytic Uremic Syndrome (HUS) Alexion Pharmaceuticals, DRI Capital, Lonza (LZAGY) Inc.

191949 Vyxeos Acute Lymphocytic Leukemia (ALL) Celator Pharmaceuticals, Inc.

192013 Selinexor Diffuse Large B-Cell Lymphoma Karyopharm Therapeutics (DLBCL) - NHL

192015 Selinexor Acute Myelogenous Leukemia (AML) Karyopharm Therapeutics

192016 Selinexor Multiple Myeloma (MM) Karyopharm Therapeutics

192025 BL-8040 Acute Myelogenous Leukemia (AML) BioLineRx Ltd. Biokine

192344 Melflufen Multiple Myeloma (MM) Oncopeptides AB

192613 Pinometostat Acute Lymphocytic Leukemia (ALL) Epizyme, Inc. Celgene (CELG)

Datamonitor Healthcare Trialtrove Biomedtracker 32 Pharma intelligence | Pharma intelligence | Pharma intelligence | 191535 TGR-1202 Chronic Lymphocytic Leukemia TG Therapeutics, Inc. Rhizen Pharmaceuticals (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

191537 Cerdulatinib Hematologic Cancer Nicox S.A. Portola (PTLA)

191548 Ninlaro Multiple Myeloma (MM) Takeda Pharmaceutical Company Ltd

191577 Ublituximab Mantle Cell Lymphoma - NHL TG Therapeutics, Inc. Ildong Pharmaceutical, LFB Group

191581 Qinprezo Acute Myelogenous Leukemia (AML) Sunesis Pharmaceuticals, Sumitomo Dainippon Pharma Inc. (4506:JP)

191592 Qinprezo Myelodysplastic Syndrome (MDS) Sunesis Pharmaceuticals, Sumitomo Dainippon Pharma Inc. (4506:JP)

191611 SGN-CD33A Acute Myelogenous Leukemia (AML) Seattle Genetics, Inc.

191632 Blincyto Acute Lymphocytic Leukemia (ALL) Amgen, Inc. Astellas (4503:JP), AstraZeneca (AZN), Dr. Reddy's (RDY)

191652 Blincyto Acute Lymphocytic Leukemia (ALL) Amgen, Inc. Astellas (4503:JP), AstraZeneca (AZN), Dr. Reddy's (RDY)

191654 Tazemetostat Non-Hodgkin's Lymphoma (NHL) Epizyme, Inc. Eisai (ESALY)

191697 Blincyto Acute Lymphocytic Leukemia (ALL) Amgen, Inc. Astellas (4503:JP), AstraZeneca (AZN), Dr. Reddy's (RDY)

191738 Jakafi Polycythemia Vera (PV) Incyte Corporation Novartis (NVS)

191749 ATIR Graft vs. Host Disease (GVHD) Kiadis Pharma B.V. Pfizer (PFE)

191764 JCAR015 Acute Lymphocytic Leukemia (ALL) Juno Therapeutics Inc.

191765 Fitusiran Hemophilia A and B - General Alnylam Pharmaceuticals, Sanofi (SNY) Clotting Products Inc.

191774 JCAR014 Hematologic Cancer Juno Therapeutics Inc. Celgene (CELG)

191777 SL-401 Blastic Plasmacytoid Dendritic Cell Stemline Therapeutics, Neoplasm (BPDCN) Inc.

191783 Venetoclax Chronic Lymphocytic Leukemia AbbVie Inc. Roche (RHHBF) (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

191788 Venetoclax Multiple Myeloma (MM) AbbVie Inc. Roche (RHHBF)

191792 Venetoclax Chronic Lymphocytic Leukemia AbbVie Inc. Roche (RHHBF) (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

191795 Darzalex Multiple Myeloma (MM) Johnson & Johnson Genmab (GEN:DC)

191800 ERY-ASP Acute Lymphocytic Leukemia (ALL) ERYTECH Pharma SA Recordati (REC.MI)

191807 Selinexor Multiple Myeloma (MM) Karyopharm Therapeutics

191810 BP-100-1.01 Acute Myelogenous Leukemia (AML) Bio-Path Holdings, Inc.

191813 ERY-ASP Acute Lymphocytic Leukemia (ALL) ERYTECH Pharma SA Recordati (REC.MI)

191815 Pracinostat Myelodysplastic Syndrome (MDS) MEI Pharma, Inc. S*BIO

191817 Estybon (Oral) Acute Myelogenous Leukemia (AML) Onconova Therapeutics, Baxalta (BXLT), SymBio Inc. (4582:JP)

191818 Iclusig Chronic Myelogenous Leukemia ARIAD Pharmaceuticals, Angelini, Endo (ENDP), Gen Ilac, (CML) Inc. Medison, Otsuka (4768:JP), PDL BioPharma (PDLI), Specialised Therapeutics Australia

Datamonitor Healthcare Trialtrove Biomedtracker 33 Pharma intelligence | Pharma intelligence | Pharma intelligence | 191819 Keytruda Hodgkin's Lymphoma Merck & Co., Inc.

191821 Actimab-A Acute Myelogenous Leukemia (AML) Actinium Pharmaceuticals, Inc.

191823 Jakafi Myelofibrosis (MF) Incyte Corporation Novartis (NVS)

191826 Keytruda Hodgkin's Lymphoma Merck & Co., Inc.

191827 Adcetris Diffuse Large B-Cell Lymphoma Seattle Genetics, Inc. Takeda (4502:JP) (DLBCL) - NHL

191831 CTL019 Acute Lymphocytic Leukemia (ALL) Novartis AG Regenerex, UPenn

191832 Farydak Myelofibrosis (MF) Novartis AG

191835 Luspatercept Anemia Acceleron Pharma, Inc. Celgene (CELG)

191837 Farydak Multiple Myeloma (MM) Novartis AG

191838 Empliciti Multiple Myeloma (MM) Bristol-Myers Squibb AbbVie (ABBV) Company

191840 Jakafi Myelofibrosis (MF) Incyte Corporation Novartis (NVS)

191844 Estybon (Oral) Myelodysplastic Syndrome (MDS) Onconova Therapeutics, Baxalta (BXLT), SymBio Inc. (4582:JP)

191847 Opdivo Hodgkin's Lymphoma Bristol-Myers Squibb Celgene (CELG), Ono (4528:JP) Company

191849 Adcetris Hodgkin's Lymphoma Seattle Genetics, Inc. Takeda (4502:JP)

191850 Adcetris Hodgkin's Lymphoma Seattle Genetics, Inc. Takeda (4502:JP)

191854 Adcetris Hodgkin's Lymphoma Seattle Genetics, Inc. Takeda (4502:JP)

191916 Keytruda Hodgkin's Lymphoma Merck & Co., Inc.

191934 Non-Viral CAR-T Cancer Intrexon Corporation Merck KGaA (MKGAY), MD Program Anderson, ZIOPHARM (ZIOP)

192027 Venetoclax Chronic Lymphocytic Leukemia AbbVie Inc. Roche (RHHBF) (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

192028 CAT-8015 Hairy Cell Leukemia AstraZeneca PLC

192346 PVX-410 Multiple Myeloma (MM) OncoPep, Inc.

192451 Acalabrutinib Chronic Lymphocytic Leukemia Acerta Pharma BV Merck (MRK) (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

192452 TGR-1202 Non-Hodgkin's Lymphoma (NHL) TG Therapeutics, Inc. Rhizen Pharmaceuticals

191618 Kyprolis Multiple Myeloma (MM) Amgen, Inc. Dr. Reddy's (RDY), Ligand (LGND), Ono (4528:JP)

191892 Alprolix Hemophilia B Biogen, Inc. Swedish Orphan Biovitrum (SOBI:ST), UCB (UCB:BB)

191675 Xarelto Venous Thromboembolism (VTE) Johnson & Johnson Bayer (BAYRY)

191794 Iclusig Chronic Myelogenous Leukemia ARIAD Pharmaceuticals, Angelini, Endo (ENDP), Gen Ilac, (CML) Inc. Medison, Otsuka (4768:JP), PDL BioPharma (PDLI), Specialised Therapeutics Australia

191879 Eloctate Hemophilia A Biogen, Inc. Swedish Orphan Biovitrum (SOBI:ST), UCB (UCB:BB)

191608 Adynovate Hemophilia A Baxalta Incorporated Nektar (NKTR)

Datamonitor Healthcare Trialtrove Biomedtracker 34 Pharma intelligence | Pharma intelligence | Pharma intelligence | 191718 Darzalex Multiple Myeloma (MM) Johnson & Johnson Genmab (GEN:DC)

191613 Adynovate Hemophilia A Baxalta Incorporated Nektar (NKTR)

191576 Gazyva Indolent Non-Hodgkin's Lymphoma - Roche Holding AG Biogen (BIIB), Chugai (4519:JP), NHL Nippon Shinyaku (4516:JP), PDL BioPharma (PDLI)

191649 Gazyva Chronic Lymphocytic Leukemia Roche Holding AG Biogen (BIIB), Chugai (4519:JP), (CLL)/Small Cell Lymphocytic Nippon Shinyaku (4516:JP), PDL Lymphoma (SLL) - NHL BioPharma (PDLI)

191757 Kyprolis Multiple Myeloma (MM) Amgen, Inc. Dr. Reddy's (RDY), Ligand (LGND), Ono (4528:JP)

191829 Tasigna Chronic Myelogenous Leukemia Novartis AG (CML)

191848 Copanlisib Indolent Non-Hodgkin's Lymphoma - Bayer AG NHL

191568 nCounter Dx Analysis Diffuse Large B-Cell Lymphoma NanoString Technologies Celgene (CELG) System (DLBCL) - NHL Inc

191766 Isatuximab Multiple Myeloma (MM) Sanofi ImmunoGen (IMGN)

191772 Venetoclax Chronic Lymphocytic Leukemia AbbVie Inc. Roche (RHHBF) (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

192446 Zydelig Chronic Lymphocytic Leukemia Gilead Sciences, Inc. (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

191619 Gazyva Chronic Lymphocytic Leukemia Roche Holding AG Biogen (BIIB), Chugai (4519:JP), (CLL)/Small Cell Lymphocytic Nippon Shinyaku (4516:JP), PDL Lymphoma (SLL) - NHL BioPharma (PDLI)

191767 Tasigna Chronic Myelogenous Leukemia Novartis AG (CML)

191771 Farydak Multiple Myeloma (MM) Novartis AG

191642 Pracinostat Acute Myelogenous Leukemia (AML) MEI Pharma, Inc. S*BIO

191793 GALE-401 Essential Thrombocythemia (ET) Galena Biopharma, Inc.

191575 ACH-4471 Paroxysmal Nocturnal Achillion Pharmaceuticals, Hemoglobinuria (PNH) Inc.

191588 ADCT-301 Hematologic Cancer ADC Therapeutics SA Genmab (GEN:DC)

191602 ADCT-402 Non-Hodgkin's Lymphoma (NHL) ADC Therapeutics SA

191603 ADCT-402 Acute Lymphocytic Leukemia (ALL) ADC Therapeutics SA

191604 CB-839 Hematologic Cancer Calithera Biosciences, Inc.

191620 GMI-1271 Multiple Myeloma (MM) GlycoMimetics, Inc.

191710 UCARTCS1 Multiple Myeloma (MM) Cellectis S.A. MD Anderson Cancer Center

191711 XmAb (Amgen) Multiple Myeloma (MM) Amgen, Inc. Xencor (XNCR)

191714 CB-5083 Solid Tumors Cleave Biosciences

191715 IMGN529 Diffuse Large B-Cell Lymphoma ImmunoGen, Inc. (DLBCL) - NHL

191716 ProTmune Hematologic Cancer Fate Therapeutics, Inc.

191727 RA101495 Paroxysmal Nocturnal Ra Pharmaceuticals, Inc. Hemoglobinuria (PNH)

Datamonitor Healthcare Trialtrove Biomedtracker 35 Pharma intelligence | Pharma intelligence | Pharma intelligence | 191732 PRTX-100 Immune Thrombocytopenic Purpura Protalex, Inc. (ITP)

191739 Vepoloxamer Sickle Cell Anemia Mast Therapeutics, Inc. CytRx Corporation (CYTR)

191799 BPX-401 Hematologic Cancer Bellicum Pharmaceuticals, Inc.

191846 VLX157 Mantle Cell Lymphoma - NHL Vivolux AB

192046 APTO-253 Acute Myelogenous Leukemia (AML) Aptose Biosciences Inc.

192465 BPX-601 Pancreatic Cancer Bellicum Pharmaceuticals, Astellas (4503:JP) Inc.

191542 bb2121 Multiple Myeloma (MM) Celgene Corporation bluebird bio (BLUE)

191580 SB-FIX Hemophilia B Sangamo Biosciences, Inc.

191626 AFM13 Hodgkin's Lymphoma Affimed N.V.

191633 AFM11 Acute Lymphocytic Leukemia (ALL) Affimed N.V.

191635 AFM11 Non-Hodgkin's Lymphoma (NHL) Affimed N.V.

191636 AFM12 Non-Hodgkin's Lymphoma (NHL) Affimed N.V.

191653 DX-4012 Venous Thromboembolism (VTE) Dyax Corp

191666 MOR202 Multiple Myeloma (MM) MorphoSys AG

191668 Betalutin Indolent Non-Hodgkin's Lymphoma - Nordic Nanovector AS NHL

191682 SGN-CD123A Acute Myelogenous Leukemia (AML) Seattle Genetics, Inc.

191729 TP-0903 Cancer Tolero Pharmaceuticals, Inc.

191733 TTI-621 Acute Myelogenous Leukemia (AML) Trillium Therapeutics Inc.

191741 Vepoloxamer Sickle Cell Anemia Mast Therapeutics, Inc. CytRx Corporation (CYTR)

191745 NEOD001 Amyloidosis Prothena Corporation plc

191748 BB-001 Chronic Lymphocytic Leukemia Bullet Biotechnology (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

191756 NK Cell Cancer Cancer Fate Therapeutics, Inc. Immunotherapy Program

191780 PLX-R18 Acute Radiation Syndrome (ARS) Pluristem Therapeutics Inc.

191998 Coversin Paroxysmal Nocturnal Akari Therapeutics, Plc Hemoglobinuria (PNH)

192047 KPT-9274 Acute Myelogenous Leukemia (AML) Karyopharm Therapeutics

192217 TP-0184 Anemia Tolero Pharmaceuticals, Inc.

189225 Iclusig Diffuse Large B-Cell Lymphoma ARIAD Pharmaceuticals, Angelini, Endo (ENDP), Gen Ilac, (DLBCL) - NHL Inc. Medison, Otsuka (4768:JP), PDL BioPharma (PDLI), Specialised Therapeutics Australia

191593 GMI-1271 Acute Myelogenous Leukemia (AML) GlycoMimetics, Inc.

191644 GMI-1359 Acute Myelogenous Leukemia (AML) GlycoMimetics, Inc.

Datamonitor Healthcare Trialtrove Biomedtracker 36 Pharma intelligence | Pharma intelligence | Pharma intelligence | 191752 TNT009 Inflammatory Disorders True North Therapeutics, Inc.

191776 Inecalcitol Chronic Myelogenous Leukemia Hybrigenics SA (CML)

191778 TGR-1202 Chronic Lymphocytic Leukemia TG Therapeutics, Inc. Rhizen Pharmaceuticals (CLL)/Small Cell Lymphocytic Lymphoma (SLL) - NHL

191785 Pacritinib Acute Myelogenous Leukemia (AML) CTI BioPharma Baxalta (BXLT), S*BIO Corporation

191791 BPX-401 Hematologic Cancer Bellicum Pharmaceuticals, Inc.

191798 ID-G100 Non-Hodgkin's Lymphoma (NHL) Immune Design Corporation

191805 IMGN779 Acute Myelogenous Leukemia (AML) ImmunoGen, Inc.

191811 RA101495 Paroxysmal Nocturnal Ra Pharmaceuticals, Inc. Hemoglobinuria (PNH)

191824 Luspatercept Myelodysplastic Syndrome (MDS) Acceleron Pharma, Inc. Celgene (CELG)

191825 BLU-285 Acute Myelogenous Leukemia (AML) Blueprint Medicines

191830 Luspatercept Anemia Acceleron Pharma, Inc. Celgene (CELG)

191842 SGN-CD19B Non-Hodgkin's Lymphoma (NHL) Seattle Genetics, Inc.

192018 KPT-8602 Multiple Myeloma (MM) Karyopharm Therapeutics

192031 SL-801 Cancer Stemline Therapeutics, CanBas (4575:JP ) Inc.

Datamonitor Healthcare Trialtrove Biomedtracker 37 Pharma intelligence | Pharma intelligence | Pharma intelligence | Appendix: Additional ASH Content

ASH Preview: One Size Fits All Approach Is No Longer Justified In AML

Opinions Split On Newly Approved Myeloma Therapies At ASH

Novartis's Midostaurin To Fill 30 Year Void In AML Treatment

Janssen Targets Combinations As Next Step For Newly Approved Darzalex

ASH 2015: Highs And Lows In CLL

ASH 2015: First-In-Class Myeloma Highlights

Spectrum/Onxeo Move Beleodaq Into Phase III As First-Line PTCL Therapy

ASH 2015: As CAR-T Players Vie For 1st Place, Will Efficacy Trump Safety?

Merck's Keytruda Data Brighten Picture For PD-1 Inhibitors In Myeloma

Datamonitor Healthcare Trialtrove Biomedtracker 38 Pharma intelligence | Pharma intelligence | Pharma intelligence |