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NEJM publishes full analysis of Rydapt® (midostaurin) Phase III RATIFY trial in newly diagnosed FLT3-mutated acute myeloid leukemia (AML)

On June 23, 2017 Novartis reported that full results from the Rydapt [] (midostaurin) Phase III RATIFY (CALGB 10603 [Alliance]) clinical trial were published in The New England Journal of Medicine (NEJM) [1] (Press release, Novartis, JUN 23, 2017, View Source [SID1234519666]). Top-line data from this study were previously presented during the plenary session at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in 2015 [2]. New data include disease-free survival (DFS), further analysis of patients undergoing transplant and expanded safety information.

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"The data from the CALGB 10603/RATIFY trial reinforce the efficacy and safety of Rydapt in patients with FLT3-mutated AML and set the stage for a shift in the way the medical community can approach this difficult-to-treat disease," said Richard M. Stone, MD, Chief of Staff and Director of the Adult Leukemia Program at Dana-Farber Cancer Institute, and Alliance for Clinical Trials in Oncology study chair for the RATIFY trial. "This study has provided critical insights for the AML community and shows the potential of clinical research carried out by international investigators with support from both public and private sources."

Study Results Published in NEJM
In RATIFY, patients aged 18-59 years treated with Rydapt in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy experienced significant improvement in overall survival (OS) with a 22% reduction in the risk of death compared with chemotherapy plus placebo. In patients in the Rydapt arm, OS was 74.7 months [95% CI, 31.5-not reached] vs. 25.6 months [95% CI, 18.6-42.9] in the placebo arm (one-sided stratified log-rank p=0.009, HR=0.78). At four years, OS was 51.4% in the Rydapt arm, compared with 44.3% in the placebo arm [1].

The median event-free survival (EFS) was 8.2 months (95% CI, 5.4-10.7) in the Rydapt arm and 3.0 months (95% CI, 1.9-5.9) in the placebo arm (one-sided stratified log-rank p=0.002, HR=0.78). Median DFS was greater with the addition of Rydapt versus the placebo arm (26.7 months [95% CI, 19.4-not reached] vs. 15.5 months [95% CI, 11.3-23.5], respectively; p=0.01). The complete remission (CR) rate, defined as CR reported within 60 days of protocol therapy initiation, was 58.9% in the Rydapt arm and 53.5% in the placebo arm (p=0.15). The benefit of Rydapt on OS and EFS was consistent across all FMS-like tyrosine kinase 3 (FLT3) mutation subgroups, including internal tandem duplication (ITD) and tyrosine kinase domain (TKD) FLT3 mutations [1].

"The Rydapt RATIFY trial is a testament to Novartis’ dedication to exploring opportunities to create therapies for patients with difficult to treat diseases," said Vasant Narasimhan, Global Head of Drug Development and Chief Medical Officer, Novartis. "These results represent the culmination of years of work and dedication from investigators around the world who were driven to find a targeted treatment for these patients."

More patients in the Rydapt arm were able to undergo allogenic hematopoietic stem cell transplantation (HCT) during their first complete response versus placebo (28.1% vs. 22.7%, respectively; p=0.10). When censoring patients at the time of transplant (when protocol therapy was discontinued), OS was numerically better for those in the Rydapt arm versus placebo arm, with a 24.3% reduction in the risk of death at four years (63.7% vs. 55.7% respectively, p=0.08) [1].

The most frequent Grade 3 to 5 non-hematologic adverse events (AEs) (incidence greater than or equal to 20%) in the Rydapt arm were febrile neutropenia and infection. In the placebo arm, the most common AEs were febrile neutropenia, infection and lymphopenia. There were few significant differences (greater than 5%) observed in the overall rate of Grade 3 to 5 AEs between the treatment arms – patients receiving Rydapt experienced higher rates of anemia and rash [1]. Please see below for additional important US safety information [3].

RATIFY, the largest clinical trial in FLT3-mutated AML to date, included 3,277 patients screened and 717 study participants from around the world. The full data from the randomized Phase III trial have now been published and include data outside the parameters of the US Prescribing Information and Swiss Product Information. Based on data from the RATIFY clinical trial, The National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines []) for AML now include use of midostaurin in FLT3-mutated AML [4].

About AML
AML, a rare and aggressive cancer of the blood and bone marrow, is the most common acute leukemia in adults. It accounts for approximately 25% of all adult leukemias worldwide, with the highest incidence rates occurring in the US, Europe and Australia [5]. It also has the lowest survival rate of all adult leukemias [5].

AML prevents white blood cells from maturing, causing an accumulation of "blasts," which do not allow room for the normal blood cells [6]. Mutations in specific genes are found in many cases of AML [7], and genetic testing for mutations in newly diagnosed AML patients can help to determine prognosis and potential treatment strategies [8].

Approximately one-third of AML patients will have a FLT3 gene mutation [7]. FLT3 is a type of cell-surface receptor which plays a role in increasing the number of certain blood cells [9]. The FLT3 gene mutation can result in faster disease progression, higher relapse rates and lower rates of survival than other forms of AML [7,9,10].

About Rydapt [] (midostaurin)
Rydapt [] (midostaurin) is an oral, multi-targeted inhibitor of multiple kinases, including FLT3 and KIT, which help regulate many essential cell processes, interrupting cancer cells’ ability to grow and multiply [3].

In the US, Rydapt is Food and Drug Administration (FDA)-approved for the treatment of adults with newly diagnosed AML who are FLT3 mutation-positive (FLT3+) as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation [3]. Rydapt is not indicated in the US as a single-agent induction therapy for the treatment of patients with AML. For a description of the experience with single-agent treatment beyond induction and consolidation, healthcare professionals in the US should refer to the Clinical Studies section of the US Prescribing Information (14.1) [3].
The full US Prescribing Information for Rydapt can be found at: View Source

Rydapt is also approved in Switzerland for use in combination with standard induction and consolidation chemotherapy, followed by maintenance monotherapy for treatment of newly diagnosed adult AML patients who have an FLT3 mutation. Novartis has submitted a regulatory application for Rydapt to the European Medicines Agency (EMA) and this application is currently under review.

Indications vary by country and not all indications are available in every country. The safety and efficacy profile of Rydapt has not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that Rydapt will become commercially available for additional indications anywhere else in the world.

Rydapt Important Safety Information
Patients who are allergic to midostaurin or any of the ingredients in Rydapt should not take Rydapt. If a patient taking Rydapt develops signs of an allergic reaction, they should seek medical help immediately. Signs of an allergic reaction include trouble breathing, flushing, chest pain, throat tightness, and swelling of lips, mouth or throat.

Rydapt should be not be used during pregnancy since Rydapt may harm an unborn baby. Pregnancy testing should be conducted for women who might become pregnant. Effective birth control should be used during treatment and for at least four months after stopping Rydapt. If a patient becomes pregnant or thinks she may be, the patient should tell their doctor right away. Women should not breastfeed during treatment with Rydapt and for at least four months after the final dose. Men taking Rydapt who have female partners that are able to become pregnant should use effective birth control during his treatment with Rydapt and for at least four months after the last Rydapt dose. Rydapt may cause fertility problems in women and men, which may affect their ability to have children.

Rydapt may cause lung problems that may lead to death. Patients on Rydapt who develop a new or worsening cough, shortness of breath, or chest discomfort should get medical help right away. These may be signs of serious lung problems.

Common sides effects reported during Rydapt treatment for AML included low level of white blood cells with fever (febrile neutropenia); nausea; redness, pain or ulcers inside the mouth (mucositis); vomiting; headache; bruising; muscle or bone pain; nose bleeds; device-related infection; high blood sugar levels (hyperglycemia) and upper respiratory infections.

If side effects including nausea, vomiting, and diarrhea occur, get worse or do not go away during treatment with Rydapt, patients should contact their doctor. Depending on the side effect and/or severity of the side effect that occur, their doctor may decrease their dose, temporarily stop, or completely stop treatment with Rydapt.

Patients should tell their doctor about all the medicines they take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Rydapt may affect how these medicines work or these other medicines may affect how Rydapt works.

Karyopharm Reports Updated Phase 2b SADAL Data for Selinexor in Diffuse Large B-Cell Lymphoma at the 2017 European Hematology Association Annual Meeting

On June 23, 2017 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported updated clinical data from the ongoing Phase 2b Selinexor Against Diffuse Aggressive Lymphoma (SADAL) study evaluating lead product candidate, selinexor (KPT-330), an oral Selective Inhibitor of Nuclear Export / SINE compound, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (Press release, Karyopharm, JUN 23, 2017, View Source [SID1234519665]). The data will be featured in an oral presentation at the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) taking place June 22-25, 2017 in Madrid, Spain. In the SADAL study, selinexor has achieved a 33.3% overall response rate (ORR) in patients with relapsed or refractory DLBCL after at least two prior multi-agent therapies and who are ineligible for transplantation. The observed responses continue to be durable, with a median duration of response (DOR) of greater than 7 months, including prolonged complete responses (CRs).

Updated Phase 2b SADAL Data in Relapsed or Refractory DLBCL

In the oral presentation, titled "Single Agent Oral Selinexor Exhibits Durable Responses in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) of Both GCB and Non-GCB Subtypes: The Phase 2b SADAL Study," Marie Maerevoet, MD, Institute Jules Bordet in Belgium, will present the updated Phase 2b SADAL data. Per the SADAL study protocol, the updated efficacy data were restricted to the interim analysis cohort (n=63), which were previously reported at AACR (Free AACR Whitepaper) 2017, and the updated safety results include updated data on all patients that received at least one dose of selinexor as of the data cutoff date.

Dr. Maerevoet commented, "We are highly encouraged by the impressive response rates that continue to be observed with single-agent oral selinexor in these heavily pretreated patients with DLBCL who have received two or more prior therapies and are not eligible for transplantation, and for whom no standard therapy exists. Along with being clinically active and durable, including prolonged complete responses, the 60mg dose continues to be well tolerated with a low incidence of Grade 3 or greater adverse events, which were manageable with dose modifications and standard supportive care."

A summary of the efficacy data to be presented at EHA (Free EHA Whitepaper) 2017 is outlined in the following table and described below.

Best Responses* in Patients as of 15 May 2017

Category N ORR (%) CR (%) PR (%) SD (%) PD/NE (%)
All patients 63 21 (33.3%) 9 (14.3%) 12 (19.0%) 6 (9.5%) 36 (57.1%)

60 mg 32 11 (34.4%) 4 (12.5%) 7 (21.9%) 1 (3.1%) 20 (62.5%)
100 mg 31 10 (32.2%) 5 (16.1%) 5 (16.1%) 5 (16.1%) 16 (51.6%)

GCB-Subtype 32 9 (28.1%) 4 (12.5%) 5 (15.6%) 3 (9.4%) 20 (62.5%)
Non-GCB-Subtype 31 12 (38.7%) 5 (16.1%) 7 (22.6%) 3 (9.7%) 16 (51.6%)
*Responses were adjudicated according to the Lugano Classification (Cheson, 2014) by an independent central radiological review committee. ORR=Overall Response Rate (CR+PR), DCR=Disease Control Rate (CR+PR+SD), CR=Complete Response, PR=Partial Response, SD=Stable Disease, PD=Progressive Disease, NE=Not Evaluable for Response. Responses are based on interim unaudited data for the first 63 patients (of 90 total patients enrolled as of the data cutoff date).

Based on the modified intention-to-treat analysis of the first 63 patients (median of 3 prior treatment regimens (range 2-5)), as adjudicated by an independent central radiological committee, 21 patients responded (9 patients with a CR and 12 patients with a PR) for an ORR 33.3%. An additional 6 patients experienced SD, for a disease control rate of 42.9%. The median DOR across all patients was greater than 7 months and responses tended to occur rapidly with a median of 2 months to onset. Among patients who responded, the median time on treatment was 9 months with a follow up of 12.8 months. As of the data cutoff date, 9 patients who responded remained on treatment, including 6 patients with a CR.

The median overall survival was 8 months for all patients on the study, consistent with the 6-7 month published survival data in this population, indicating that their prognosis is extremely poor. As of the data cutoff date, median survival for the patients with PR or CR had not been reached and is over 9 months; the median survival for patients with SD or PD, NE disease was 4.8 months.

Selinexor also showed robust, single-agent activity against GCB and non-GCB subtypes of DLBCL: Of the 32 patients with DLBCL of the GCB-subtype, 9 responded (4 patients with a CR, 5 patients with a PR) for an ORR of 28.1%. Of the 31 patients with DLBCL of the non-GCB (or ABC)-subtype, 12 responded (5 patients with a CR, 7 patients with a PR) for an ORR of 38.7%. Finally, amongst the 14 patients with "double-" or "triple-hit" DLBCLs, the ORR was 35%, indicating that selinexor has clear activity in this population, which usually has a particularly poor prognosis.

Among the 90 patients evaluated for safety as of the data cutoff date, the most common adverse events (AEs) across both dosing groups were fatigue (61%), nausea (51%), thrombocytopenia (50%), anorexia (49%), vomiting (31%) and anemia (30%), and were primarily grades 1 and 2 and were managed with dose modifications and/or standard supportive care. As expected, the most common grade 3 and 4 AEs in the 60mg arm were thrombocytopenia (28%), neutropenia (17%), anemia (15%), and fatigue (11%) and were manageable with dose modifications and/or standard supportive care.

As previously announced, in consultation with the U.S. Food and Drug Administration (FDA), Karyopharm has amended the SADAL study protocol to become a single-arm study focusing solely on single-agent selinexor dosed at 60mg twice weekly and has eliminated the 100mg arm. The FDA has agreed that the single-arm trial design appears appropriate for accelerated approval in DLBCL, though eligibility for accelerated approval will depend on the complete trial results and available therapies at the time of regulatory action. In total, the SADAL study is expected to enroll up to a total of 130 patients in the 60mg single-arm cohort and Karyopharm plans to report top-line results in the second half of 2018.

"The IRC-confirmed durable responses achieved with single-agent oral selinexor have improved over time and continue to demonstrate robust single-agent activity and prolonged responses in patients with heavily pretreated DLBCL, and these responses correlate with improved overall survival," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "We were particularly pleased to see a 35% response rate in the double- or triple-hit subgroup, a particularly difficult to treat patient population. The 60mg treatment arm is enrolling on track, and we look forward to reporting top-line data from the SADAL study in the second half of 2018. Assuming a positive outcome, we expect to seek accelerated approval for selinexor in DLBCL."

Details for the Oral Presentation at EHA (Free EHA Whitepaper) 2017:

Title: Single Agent Oral Selinexor Exhibits Durable Responses in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) of Both GCB and Non-GCB Subtypes: The Phase 2b SADAL Study
Presenter: Marie Maerevoet, Institute Jules Bordet, Brussels, Belgium
Abstract code: S469
Topic: Aggressive Non-Hodgkin lymphoma — Clinical
Session: Aggressive Non-Hodgkin lymphoma — Relapsed/refractory
Location: Hall C
Date and Time: Saturday, June 24, 2017 from 14:45 – 17:00 CET

About Selinexor

Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,000 patients have been treated with selinexor and it is currently being evaluated in several mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON), in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), and in diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform the Company’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

Bellicum Reports Clinical Results of BPX-501 in Pediatric Leukemias at the 22nd Congress of the European Hematology Association

On June 23, 2017 Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported data from its ongoing multicenter BP-004 trial of BPX-501 and rimiducid in a cohort of pediatric patients with acute leukemias who lack a matched donor (Press release, Bellicum Pharmaceuticals, JUN 23, 2017, View Source [SID1234519662]). Results from 47 patients demonstrated that administering BPX-501 following an alpha/beta T-cell depleted haploidentical hematopoietic stem cell transplant (alpha/beta T-cell depleted haplo-HSCT) produced rapid immune reconstitution, low incidence of acute and chronic Graft versus Host Disease (GvHD), and a low rate of disease relapse. The data will be reviewed in an oral presentation at the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) at 5 p.m. CEST on June 24 in Madrid, Spain.

"These data demonstrate that BPX-501-modified T cells can provide rapid hematological reconstitution and a potentially stronger anti-leukemic effect in children with high-risk disease than traditional T-cell depleted transplants," said Franco Locatelli, MD, PhD, Director of the Department of Hematology and Oncology at Ospedale Pediatrico Bambino Gesù in Rome, Italy. "The incidence of GvHD was low, and managed by standard treatments or the administration of rimiducid. Patients who received rimiducid experienced a recovery of the beneficial, non-reactive BPX-501 T cells. These are very encouraging early outcome results for children who need a stem cell transplant and lack a matched donor."

Summary of Results (Abstract S495)

Investigators evaluated the safety and efficacy of an infusion of BPX-501 in children with high-risk acute lymphoblastic leukemia (ALL) (n=28) and acute myeloid leukemia (AML) (n=19) following an alpha/beta T-cell depleted haplo-HSCT. Patients had a median follow-up of approximately eight months (11 months in surviving patients). Results from the three European trial sites showed:

Disease relapse rate of 14.72% in BPX-501 treated patients
Median neutrophil recovery = 16 days (9-24); median platelet engraftment = 11 days (8-19); median time to hospital discharge = 21.5 days (14-103)
Acute GvHD Grade 2-4 was 11.83%; acute GvHD Grade 3-4 was 4.70%
Chronic GvHD Grade Moderate-Severe was 3.23%
Non-relapse mortality (NRM) of 3.23% in BPX-501 patients
Re-expansion of infection-fighting BPX-501 cells after a sharp decrease following infusion of rimiducid, with no reoccurrence of GvHD
Results compare favorably to historic controls1
Commented Rick Fair, President and CEO of Bellicum Pharmaceuticals, "We are pleased by the profile observed with BPX-501 in pediatric patients receiving a haploidentical transplant, and by its potential to reduce disease relapse. These results provide important insights into the potential long-term benefits of BPX-501, and support our plans to begin a mid-stage study this year in adults with hematologic cancers, for whom lack of a matched donor and disease relapse are significant treatment challenges."

The presentation slides (abstract S495) will be made available in the Events and Presentations section of the Bellicum website shortly after the time of the presentation.

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

Positive Phase 1b Data for NewLink Genetics’ IDO Pathway Inhibitor, Indoximod, in Combination with Chemotherapy for Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Presented at the European Hematologic Association (EHA) Congress in Madrid, Spain

On June 23, 2017 NewLink Genetics Corporation (NASDAQ:NLNK) reported the presentation of data from the Phase 1b portion of a study of indoximod, an IDO pathway inhibitor, in combination with idarubicin and cytarabine for patients with newly diagnosed acute myeloid leukemia (AML) (Press release, NewLink Genetics, JUN 23, 2017, View Source [SID1234519660]). Abstract E-912, Indoximod in Combination with Idarubicin and Cytarabine for Upfront Treatment of Patients with Newly Diagnosed Acute Myeloid Leukemia (AML): Phase 1 Report, is being presented by Ashkan Emadi, M.D., Ph.D., Associate Professor of Medicine at the University of Maryland Greenebaum Comprehensive Cancer Center, during the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in Madrid, Spain on Friday, June 23, 2017, 9:30 AM to Saturday, June 24, 7:00 PM CET.

These data indicate indoximod does not appear to add significant toxicity to standard therapy for patients with newly diagnosed AML, and no regimen-limiting toxicities (RLT) have been observed to date. Initial data show that the morphological complete remission (CR) rate is as expected after one cycle of induction chemotherapy. Seven of seven patients who achieved CR were found to have no minimal residual disease (MRD-neg).

"While from a small number of patients, these data show an encouraging MRD negativity rate and may offer the potential for measurable clinical benefits for patients," said Dr. Emadi, Principal Investigator of this study.

About Indoximod
Indoximod is an investigational, orally available small molecule targeting the IDO pathway. The IDO pathway is one of the key immuno-oncology targets involved in regulating the tumor microenvironment and immune escape.

Bellicum Announces Clinical Data on BPX-501 at Presidential Symposium of the 22nd Congress of the European Hematology Association

On June 23, 2017 Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported that results will be presented today from its global BP-004 clinical trial of BPX-501 in the Presidential Symposium at the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) being held in Madrid, Spain (Press release, Bellicum Pharmaceuticals, JUN 23, 2017, View Source [SID1234519659]). Clinical results reported in pediatric patients with a wide range of genetic blood diseases and hematologic cancers suggest that BPX-501 lowers the risks associated with haploidentical stem cell transplants, increasing their acceptability for more patients who could benefit but lack a matched donor. The EHA (Free EHA Whitepaper)’s Presidential Symposium showcases the top abstracts selected by the Scientific Program Committee each year.

"The vast majority of patients in this study experienced successful engraftment, no or low grade GvHD, rapid immune recovery and early hospital discharge," said Dr. Franco Locatelli, MD, PhD, Director of the Department of Pediatric Hematology and Oncology, Ospedale Pediatrico Bambino Gesù (OPBG), Rome. "All cases of uncontrolled acute GvHD were resolved by administration of rimiducid to activate the CaspaCIDe safety switch incorporated in BPX-501. With low incidence of transplant-related mortality and manageable GvHD, these data suggest that the addition of BPX-501 T cells could represent a meaningful advance for patients in need of a transplant but who lack a matched related donor."

Updated Results of BP-004 Study in Global and EU Populations

Investigators reported on pediatric patients with hematologic cancers and genetic blood diseases who underwent treatment with BPX-501 after an alpha/beta T-cell depleted haploidentical hematopoietic stem cell transplant (alpha/beta T-cell depleted haplo-HSCT) and had at least six months of follow-up. Investigators reviewed overall data on 98 patients from 12 centers in the U.S. and Europe, as well as on the subset of 61 patients at European sites.

At the 180-day measurement time point, cumulative incidence of transplant-related mortality (TRM) was 5% in the overall patient population. A significant reduction in viral infections and reinfections was observed with BPX-501 compared to results from a study in Rome (OPBG) in patients undergoing an alpha/beta T-cell depleted haplo-HSCT without the addition of BPX-501 (n=107). Additionally, there were no reported adverse events associated with the use of BPX-501 or rimiducid. At six months of follow-up, the cumulative incidence of Grade 2-4 acute Graft versus Host Disease (GvHD) was 13 percent. The cumulative incidence of chronic GvHD was three percent at one year of follow-up.

The administration of rimiducid was required in 11 patients with acute GvHD who did not respond to standard treatments. In all 11 cases, rimiducid rapidly resolved the GvHD. In addition, the non-reactive T cells recovered, with no recurrence of GvHD.

Data from the subset of 61 patients from European sites were also reviewed in the presentation. At six months of follow-up there was no transplant-related mortality. Cumulative GvHD incidence remains low, with incidence rates of 10 percent for Grade 2-4 acute GvHD, and three percent for Grade 3-4 acute GvHD. There was no persistent chronic GvHD.

"Data from our global BP-004 study continue to show consistent and strong overall outcomes across a wide range of diseases, suggesting the potential to enable curative stem cell transplants from partially matched donors for more children," said Rick Fair, President and CEO of Bellicum Pharmaceuticals. "Data from this ongoing BP-004 study in Europe, along with comparative data from an observational trial of pediatric patients undergoing a stem cell transplant from matched unrelated donors, are expected to support the filing of a European Marketing Authorization Application in mid-2018."

Patient Populations Included in Study, By Disease Type

Genetic Blood Diseases (n=59) Hematologic Cancers (n=39)
Primary immune deficiencies (n=26) Acute lymphoblastic leukemia (ALL) (n=21)
Thalassemia major (n=8) Acute myeloid leukemia (AML) (n=14)
Hemophagocytic lymphohistiocytosis (HLH) (n=6) Other (n=4)
Sickle cell disease (n=5)
Other (n=14)

Hemoglobinopathies and Erythroid Disorders Poster Presentation
Also today at the 22nd Congress of EHA (Free EHA Whitepaper), updated results will be presented in patients with hemoglobinopathies and erythroid disorders, including five patients with sickle cell disease, in a poster presentation titled: "The Use of BPX-501 Donor T-Cell Infusion (with Inducible Caspase 9 Suicide Gene) Together with HLA-Haploidentical Stem Cell Transplant to Treat Children with Hemoglobinopathies and Erythroid Disorders."

All 15 patients in the cohort showed normal hemoglobin levels and remained transfusion-free at 180 days, with no transplant-related mortality.

The Presidential Symposium oral presentation (abstract S146) will take place today, June 23 at 3:45 – 4:00 PM CEST (9:45-10:00 AM EDT) and the poster (abstract P381) will be reviewed today at 5:15 – 6:45 PM CEST (11:15 AM – 12:45 PM EDT). Both presentations will be made available in the Events and Presentations section of the Bellicum website shortly after the time of the respective presentation.

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