On December 11, 2017 Seattle Genetics, Inc. (NASDAQ:SGEN) and Bristol-Myers Squibb Company (NYSE:BMY) reported highlighted updated interim results from an ongoing phase 1/2 clinical trial evaluating the combination of ADCETRIS (brentuximab vedotin) and Opdivo (nivolumab) in relapsed or refractory classical Hodgkin lymphoma (HL) at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place in Atlanta, Georgia, December 9-12, 2017 (Press release, Seattle Genetics, DEC 11, 2017, View Source;p=RssLanding&cat=news&id=2322109 [SID1234522562]). The data were also simultaneously published online in the journal Blood. The data reported from 62 patients, including 60 evaluable for response, were featured in an oral presentation and selected to be included in the 2018 Highlights of ASH (Free ASH Whitepaper) post-meeting program. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL that plays a role in tumor growth and survival. Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to harness the body’s own immune system to help restore anti-tumor immune response. ADCETRIS and Opdivo are not approved in combination for the treatment of relapsed or refractory HL or for other indications.

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"The phase 1/2 study combining the antibody-drug conjugate ADCETRIS with the PD-1 immune checkpoint inhibitor Opdivo is a promising investigational approach as it combines a CD30-targeted therapy with a therapy designed to activate the immune system. The antitumor activity of the drugs may be enhanced when administered in combination," said Alex Herrera, M.D., lead trial investigator and assistant professor at the City of Hope Medical Center, Duarte, California. "The interim results evaluating the combination regimen in relapsed or refractory HL patients continue to look compelling, demonstrating both promising activity in addition to a manageable overall safety profile. These data support further exploration of this novel, chemotherapy-free investigational regimen in HL patients."

"We are evaluating ADCETRIS broadly as the foundation of care for CD30-expressing lymphomas, including combination strategies that have the potential to improve efficacy. At this year’s ASH (Free ASH Whitepaper) Annual Meeting, we are presenting significant clinical updates that support this goal, including results from the phase 3 ECHELON-1 clinical trial evaluating ADCETRIS in combination with chemotherapy in frontline HL as well as interim results from this phase 1/2 study evaluating ADCETRIS in combination with Opdivo in relapsed HL," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "Interim results from the trial evaluating ADCETRIS in combination with Opdivo as pre-transplant salvage therapy for classical HL patients continue to look promising, demonstrating an 83 percent objective response rate, with a 62 percent complete response rate and an acceptable safety profile. We look forward to further evaluation of this innovative combination regimen in other disease settings, including the ongoing pivotal phase 3 CHECKMATE 812 study in patients with relapsed HL, in partnership with Bristol-Myers Squibb."

"Our ongoing collaboration to evaluate Opdivo in combination with Seattle Genetics’ ADCETRIS reinforces Bristol-Myers Squibb’s commitment to addressing cancer from all angles for patients with high unmet needs," said Fouad Namouni, M.D., head of Oncology Development, Bristol-Myers Squibb. "We look forward to further evaluation of the ADCETRIS and Opdivo combination in Hodgkin lymphoma and other hematologic malignancies in several ongoing trials."

Interim Results from a Phase 1/2 Study of Brentuximab Vedotin in Combination with Nivolumab in Patients with Relapsed or Refractory Hodgkin Lymphoma (Abstract #649, oral presentation at 10:30 a.m. ET)

Data were reported from 62 patients with relapsed or refractory HL who received the combination regimen of ADCETRIS plus Opdivo after failure of frontline therapy. Patients were treated once every three weeks, with up to four cycles of combination therapy in the outpatient setting. After completion of the fourth cycle of treatment, patients were eligible to undergo an autologous stem cell transplant (ASCT). The median age of patients was 36 years. The majority of patients (95 percent) were refractory or had relapsed after receiving the standard of care frontline treatment ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine) or some variation of the standard of care (ABVE-PC, R-ABVD).

Key findings presented include:

Of 60 response-evaluable patients, 50 patients (83 percent) had an objective response, including 37 patients (62 percent) with a complete response and 13 patients (22 percent) with a partial response. Five patients (eight percent) had stable disease and five patients (eight percent) had progressive disease. Median follow-up time was eight months and median duration of response was not yet reached. The estimated six-month progression-free survival rate was 89 percent.
Of the 62 patients enrolled, 58 patients completed all four cycles of study treatment and four patients discontinued prior to the end of treatment. At the time of data analysis, 54 patients received an ASCT. Preliminary analysis shows no impact of combination treatment with ADCETRIS and Opdivo on stem cell mobilization or engraftment.
The most common adverse events (AEs) of any grade occurring prior to ASCT or subsequent salvage therapy in at least 20 percent of patients were nausea, fatigue, infusion-related reaction (IRR), pruritus, diarrhea, headache, cough, vomiting, dyspnea, nasal congestion, pyrexia and rash. Grade 3 or 4 adverse events occurred in 19 patients (31 percent), with 17 patients (28 percent) having Grade 3 AEs (fatigue, IRR, pruritus and diarrhea) and two patients (three percent) having Grade 4 AEs (thrombocytopenia and increased lipase).
Infusion-related reactions (IRRs) were observed in 44 percent of patients, of which the majority (41 percent) were Grade 1 or 2. No patients discontinued treatment due to an IRR.
Potential immune-related adverse events, excluding IRRs, occurred in 50 patients (82 percent), and five patients required treatment with systemic steroids, including patients with Grade 3 diarrhea and Grade 2 colitis, Grade 3 aspartate aminotransferase elevation, Grade 4 colitis and pneumonitis (after receiving additional salvage therapy), Grade 2 pneumonitis, and Grade 4 pneumonitis (after BEAM, as part of the conditioning regimen). No patients discontinued treatment due to an immune-related adverse event.
ADCETRIS and Opdivo are being evaluated as combination therapy in multiple ongoing clinical trials. In addition to the study presented at ASH (Free ASH Whitepaper), a trial titled "A Safety and Effectiveness Study of Nivolumab in Combination With Brentuximab Vedotin to Treat Non-Hodgkin Lymphomas" is ongoing and enrolling patients with relapsed or refractory disease, including diffuse large B-cell lymphoma (DLBCL), and other rare subtypes of B-cell lymphoma, including mediastinal B-cell lymphoma and mediastinal gray zone lymphoma. The companies have also extended the clinical evaluation of ADCETRIS and Opdivo into a clinical trial evaluating the combination as frontline treatment for older HL patients. Lastly, the companies initiated a pivotal phase 3 clinical trial called CHECKMATE 812 trial evaluating ADCETRIS alone versus ADCETRIS in combination with Opdivo in relapsed/refractory HL patients.

About Classical Hodgkin Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system and is the most common type of blood cancer. There are two major categories of lymphoma: HL, also known as Hodgkin disease, and non-Hodgkin lymphoma. HL is a cancer that starts in white blood cells called lymphocytes, which are part of the body’s immune system. The disease is most often diagnosed in early adulthood (ages 20-40) and late adulthood (older than 55 years of age). Classical Hodgkin lymphoma is the most common type of HL, accounting for 95% of cases. Classical HL is distinguished from other lymphomas by the characteristic presence of CD30-positive Reed-Sternberg cells.

According to the American Cancer Society, approximately 8,260 cases of Hodgkin lymphoma will be diagnosed in the United States during 2017 and more than 1,000 will die from the disease. According to the Lymphoma Coalition, over 62,000 people worldwide are diagnosed with Hodgkin lymphoma each year and approximately 25,000 people die each year from this cancer.

About ADCETRIS

ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30 and is being evaluated broadly in more than 70 clinical trials, including three phase 3 studies: the completed ECHELON-1 trial in frontline classical Hodgkin lymphoma that supported the recent FDA Breakthrough Therapy Designation and submission of the supplemental Biologics License Application (BLA) for use in this setting, the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, and the ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS injection for intravenous infusion has received FDA approval for four indications: (1) regular approval for adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy, (2) regular approval for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (3) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (4) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-ASCT consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. The European Commission extended the current conditional marketing authorization of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT.

ADCETRIS has received marketing authorization by regulatory authorities in 69 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo + Yervoy combination was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

On December 11, 2017 Atara Biotherapeutics, Inc. (Nasdaq:ATRA), a leading off-the-shelf T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported that the Company’s collaborating investigators presented updated, positive interim results for tabelecleucel (formerly known as ATA129) from a multicenter expanded access protocol (EAP) study for patients with EBV associated cancers (Press release, Atara B59thiotherapeutics, DEC 11, 2017, View Source [SID1234522568]). The findings were reported at the ongoing 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place in Atlanta, GA, December 9-12, 2017. Tabelecleucel is Atara’s off-the-shelf T-cell immunotherapy in development for the treatment of Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorder (EBV+PTLD), as well as other EBV associated hematologic and solid tumors.

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"We are gratified to see that the multicenter clinical findings in patients with EBV+PTLD are consistent with the tabelecleucel profile observed in the Phase 2 studies conducted at Memorial Sloan Kettering Cancer Center," said Chris Haqq M.D., Ph.D., Executive Vice President of Research and Development and Chief Scientific Officer of Atara Biotherapeutics. "We look forward to initiating Phase 3 clinical studies with tabelecleucel by the end of this year, which are expected to enroll the same EBV+PTLD patient populations as presented at ASH (Free ASH Whitepaper)."

Updated efficacy findings were presented:

In 6 patients with rituximab-refractory EBV+PTLD following solid organ transplant (SOT) the Objective Response Rate (ORR) was 83%, with 5 of 6 patients responding to treatment.
Additionally, in 5 patients with rituximab-refractory EBV+PTLD following allogeneic hematopoietic cell transplant (HCT) an ORR of 80% was observed, with 4 of 5 patients responding to treatment.
An additional patient with EBV+PTLD following HCT remains alive, but was not evaluable due to lack of post-baseline assessment.
The estimated one-year overall survival for the 12 tabelecleucel treated patients with EBV+PTLD following HCT or SOT, was 90.9% [95% confidence interval (50.8%, 98.7%)].
Updated safety findings were reported for a total of 23 patients, including an additional 11 patients with other EBV associated cancers who were included in the safety analysis:

Tabelecleucel was generally well-tolerated in this study population, which comprised quite ill, mostly immunosuppressed patients with multiple comorbidities.
5 patients experienced treatment-related serious adverse events (SAEs).
One HCT patient died due to PTLD disease progression.
Two possibly related cases of graft-versus-host disease (GvHD) in patients with EBV+PTLD following HCT were reported.
A tumor flare was observed in one patient with EBV+ HIV-associated plasmablastic lymphoma that resolved without clinical sequelae.
Atara’s collaborating investigators at Memorial Sloan Kettering Cancer Center presented updated results for ATA230, an allogeneic T-cell immunotherapy targeting antigens expressed by cytomegalovirus (CMV), from 50 post-transplant patients with refractory CMV viremia and disease, including those with disease in the CNS. The reported response rate of 64% in all patients was similar in those with CMV viremia and disease. Patients who responded to ATA230 showed improved 6-month survival of 81.3% versus 33.3% in patients who did not respond to treatment. One of the 32 patients who responded to ATA230 died of CMV disease. ATA230 was generally well-tolerated. Five patients experienced grade 4 or 5 serious adverse events deemed possibly related to ATA230.

About EBV+PTLD
Since its discovery as the first human oncovirus, Epstein-Barr virus (EBV) has been implicated in the development of a wide range of lymphoproliferative disorders, including lymphomas and other cancers. EBV is widespread in all human populations and persists as a lifelong, asymptomatic infection. In immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplants (HCT) or solid organ transplants (SOT), EBV associated post-transplant lymphoproliferative disorder (EBV+PTLD), represents a life-threatening condition. Median overall survival in patients with EBV+PTLD following HCT who have failed rituximab-based first line therapy is 16-56 days. In EBV+PTLD following SOT, patients failing rituximab experience increased chemotherapy-induced treatment-related mortality compared to other lymphoma patients. One- and two-year survival in patients with high-risk EBV+PTLD following SOT is 36% and 0%, respectively.

About tabelecleucel (formerly known as ATA129)
Atara’s most advanced T-cell immunotherapy in development, tabelecleucel, is a potential treatment for patients with rituximab-refractory Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorder (EBV+PTLD), as well as other EBV associated hematologic and solid tumors, including nasopharyngeal carcinoma (NPC). In February 2015, FDA granted tabelecleucel Breakthrough Therapy Designation for EBV+PTLD following allogeneic hematopoietic cell transplant (HCT) and in October 2016, tabelecleucel was accepted into the EMA Priority Medicines (PRIME) regulatory pathway for the same indication, providing enhanced regulatory support. Atara also received positive regulatory feedback from Health Canada in September 2017 supporting the submission of tabelecleucel for an expedited approval pathway. In addition, tabelecleucel has orphan status in the U.S. and EU. Phase 3 studies of tabelecleucel in EBV+PTLD following HCT (MATCH study) or solid organ transplant (ALLELE study) are expected to start in 2017, and a Phase 1/2 study in NPC is planned for 2018. Tabelecleucel is also available to eligible patients with EBV associated hematologic and solid tumors through an ongoing multicenter expanded access protocol (EAP) clinical study.

About CMV
In patients with weakened immune systems, including bone marrow and solid organ transplant recipients, newborns with immature immune systems and those with human immunodeficiency virus (HIV), cytomegalovirus (CMV) can cause potentially life-threatening disease or may result in blindness, brain damage, and deafness. While small molecule antiviral drugs are approved to treat and prevent CMV infection, there remains a high unmet need due to viral resistance, modest neurodevelopmental activity and adverse effects, such as toxicity and reduction in white blood cell count impairing the ability to fight other infections, with these agents.

About ATA230
ATA230, an allogeneic T-cell immunotherapy targeting antigens expressed by cytomegalovirus (CMV), has been investigated in one Phase 1 and two Phase 2 clinical studies in immunocompromised patients with CMV viremia or disease who are refractory or resistant to antiviral drug treatment in the post-transplant setting. In October 2017, Atara announced that ATA230 was granted Rare Pediatric Disease Designation by the FDA for the treatment of congenital CMV infection, and in September 2017, ATA230 received orphan drug designation in the U.S. for the treatment of CMV viremia and disease in immunocompromised patients. The European Medicines Agency (EMA) in October 2016 also issued a positive orphan drug designation opinion for ATA230 for the treatment of CMV infection in patients with impaired cell-mediated immunity. Atara intends to further evaluate ATA230 development plans with the FDA and other global health authorities following the initiation of tabelecleucel EBV+PTLD Phase 3 studies.

On December 11, 2017 MorphoSys AG (FSE: MOR; Prime Standard Segment; TecDAX, OTC: MPSYY) reported clinical data from the ongoing phase 2 clinical trial (L-MIND) evaluating MOR208 in combination with lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). DLBCL is the most frequent type of malignant lymphoma worldwide and accounts for approximately 30% of all non-Hodgkin lymphomas. Data will be reported in a poster presentation (available for download) at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, Georgia/USA. MOR208 is an investigational Fc-engineered monoclonal antibody directed against CD19 (Press release, MorphoSys, DEC 11, 2017, View Source [SID1234522518]).

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The data presented at ASH (Free ASH Whitepaper) formed the basis for the Breakthrough Therapy designation recently awarded by the FDA for MOR208, in combination with lenalidomide, for the treatment of non-transplant eligible patients with R/R DLBCL.

At data cut-off (June 13, 2017), 51 patients had been enrolled in the study, of whom 44 were evaluable for efficacy assessments. Preliminary data show an objective response in 23 out of 44 patients (ORR: 52%), 19 (83%) of whom show ongoing responses. Complete remission was seen in 14 out of 44 patients (CR: 32%). The median time to response was 1.8 months, the median time to complete response was 2.3 months. The preliminary median progression-free survival (PFS) based on Kaplan Meier calculation was 11.3 months.

No unexpected toxicities were observed for the treatment combination and no infusion-related reactions were reported for MOR208. The most frequent adverse events with a toxicity grading of 3 or higher were neutropenia, thrombocytopenia, and leukopenia, observed in 35%, 10%, and 8% of patients, respectively. Pneumonia and hypokalemia were reported for 10% and 8% of the patients. To date, 45% of patients required a reduction of their lenalidomide dose, from a starting dose of 25mg daily.

The trial has recently completed patient recruitment as required by the study protocol. To date, 81 patients have been enrolled.

"We are very encouraged by the updated clinical trial results from the ongoing L-MIND trial, especially the complete responses and the duration of responses we have seen so far. DLBCL is a very aggressive lymphoma. In particular, those patients with relapsed or refractory DLBCL who are not eligible for high-dose chemotherapy and autologous stem cell transplantation are in need of more therapeutic options. Based on the FDA Breakthrough Therapy designation we recently obtained, we intend to develop MOR208 together with lenalidomide as a potential new treatment option for this patient group as quickly as possible," commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG.

The L-MIND trial (Lenalidomide plus MOR208 in DLBCL) is a single-arm, open-label, multicenter study of MOR208 in combination with lenalidomide. The trial is enrolling patients with relapsed or refractory DLBCL after up to three prior lines of therapy, with at least one prior therapy including an anti-CD20 targeting therapy (e.g. rituximab). Patients could not be candidates for high-dose chemotherapy and autologous stem cell transplantation. Patients enrolled had a median age of 74 years.

Details of the MOR208 presentation at ASH (Free ASH Whitepaper) 2017:

Abstract #4123; Poster III

Single-Arm Phase II Study of MOR208 Combined with Lenalidomide in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: L-Mind

The poster will be presented during the session #626 "Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)-Results from Prospective Clinical Trials" on Monday, December 11, 2017, 6:00pm-8:00pm EST (Dec. 12, 2017, 0:00am-2:00am CET), in the Georgia World Congress Center, Bldg A, Lvl 1, Hall A2.

In addition to the presentation, the abstract has been published online in the December 8, 2017 supplemental volume of Blood. Additional information can be found at www.hematology.org, including the abstract.

MorphoSys will hold an investor & analyst conference call after the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting 2017 on December 12, 2017, 11:00am EST(5:00pm CET).

Dial in:
Germany: +49 89 2444 32975
United Kingdom: +44 20 3003 2666
USA: +1 202 204 1514
The presentation slides and webcast link will be available at www.morphosys.com/conference-calls. A slide-synchronized audio replay of the conference will also be available at the corporate website following the live event.

About CD19 and MOR208
CD19 is broadly and homogeneously expressed across different B cell malignancies including DLBCL and CLL. CD19 has been reported to enhance B cell receptor (BCR) signaling, which is assumed important for B cell survival, making CD19 a potential target in B cell malignancies.
MOR208 (previously Xmab(R)5574) is an investigational Fc-enhanced monoclonal antibody directed against CD19, a prominent marker present on the surface of B-cells. Fc-modification of MOR208 is intended to lead to a significant potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thus aiming to improve a key mechanism of tumor cell killing. Furthermore, MOR208 has been observed in preclinical models to induce direct apoptosis by binding to CD19, which is assumed to be a crucial component for B cell receptor (BCR) signaling.
MorphoSys AG is clinically investigating MOR208 as a therapeutic option in B cell malignancies in a number of ongoing combination trials. An open-label phase 2 combination trial (L-MIND study) was started in March 2016 and is designed to investigate the safety and efficacy of MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL. The phase 2/3 B-MIND study was started in August 2016 and transitioned into its phase 3 pivotal part in June 2017 following a recommendation of the IDMC based on the available data from the phase 2 initial safety evaluation. The B-MIND study is designed to investigate MOR208 in combination with the chemotherapeutic agent bendamustine in comparison to the combination of the anti-CD20 antibody rituximab plus bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Furthermore, MOR208 is currently being clinically investigated in combination with idelalisib or venetoclax in patients with relapsed/refractory CLL after discontinuation of a prior Bruton tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib).

On December 11, 2017 Aileron Therapeutics, the clinical-stage leader in the field of stapled peptides developing therapeutics for cancers and other diseases, reported two oral presentations of preclinical data from collaborators on ALRN-6924 in T-cell lymphomas (TCL) and acute myeloid leukemia (AML) (Press release, Aileron Therapeutics, DEC 11, 2017, View Source;p=RssLanding&cat=news&id=2322188 [SID1234522542]). ALRN-6924, a stapled peptide therapeutic, is believed to be the first product candidate undergoing clinical evaluations that has been shown to disrupt both MDMX- and MDM2-mediated inhibition of the wild type p53 tumor suppressor gene. The data were reviewed in separate oral presentations by researchers from the Dana-Farber Cancer Institute and the Albert Einstein College of Medicine during the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

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"We are encouraged by these positive preclinical data from our collaborators, which demonstrate that dual inhibition by ALRN-6924 induces strong p53 activity that leads to anti-cancer effects," said Dr. Manuel C. Aivado, Chief Medical Officer. "These data support the clinical results we saw in our Phase 1 all-comers trial, and we look forward to continuing to evaluate ALRN-6924 in our ongoing PTCL and AML clinical trials."

TCL Study Highlights (Abstract #571)

In an in vitro and in vivo preclinical study, MDMX and MDM2 were evaluated as potential targets for treating wild type p53 T-cell lymphomas by using ALRN-6924 to inhibit their expression. The data showed that ALRN-6924 induced apoptotic cell death in TCL lines, and significantly reduced tumor burden compared to the vehicle in animal models. Furthermore, ALRN-6924 had a favorable safety profile and demonstrated superior efficacy across multiple TCL subtypes compared to the current standard-of-care.

Commented David Weinstock, M.D. of Dana-Farber Cancer Institute, "Given the need for new treatment approaches for T-cell lymphomas, we evaluated ALRN-6924 in animal models and found that the compound’s dual inhibition mechanism for restoring the function of p53 showed promising activity across multiple TCL subtypes, including PTCL. Animal models in our studies displayed key markers that demonstrated consistency with on-target p53 activation and apoptosis, supporting further clinical development of ALRN-6924 for PTCL." i

AML Study Highlights (Abstract #795)

The preclinical data presented showed that dual inhibition of MDMX and MDM2 by ALRN-6924 led to activation of p53-dependent pathways in AML cells. The disruption of MDMX/p53 and MDM2/p53 interactions resulted in strong anti-leukemic effects, and induced cell cycle arrest and apoptosis in cell lines and wild type p53 AML patients’ cells. The compound exhibited strong on-target activity in AML cell lines and primary cells in vitro, as well as in a patient who received ALRN-6924. The data further demonstrated that ALRN-6924 showed superiority over MDM2-only inhibition, and led to improved survival in in vivo AML models.

"These results support our understanding that in most patients with acute myeloid leukemia, a devastating disease with limited therapeutic options, p53 is circumvented by activation of its natural suppressor proteins, MDMX and MDM2," said Ulrich Steidl, Ph.D., M.D. of the Albert Einstein College of Medicine. "The ability to reactivate the p53 pathway by inhibiting both MDMX and MDM2 using a novel therapeutic modality such as stapled peptides is an exciting new chapter in p53 research. The studies presented today strengthen the rationale for the use of ALRN-6924 in acute myeloid leukemia and other wild type p53 cancers." ii

About ALRN-6924
ALRN-6924 is a first-in-class product candidate designed to reactivate wild type p53 tumor suppression by disrupting the interactions between the two primary p53 suppressor proteins, MDMX and MDM2. Aileron believes ALRN-6924 is the first and only product candidate in clinical development that can equipotently bind to and disrupt the interaction of MDMX and MDM2 with p53. Based on preclinical data and preliminary evidence of safety and anti-tumor activity in its ongoing clinical trials, there may be a significant opportunity to develop ALRN-6924 as a monotherapy or combination therapy for a wide variety of solid and liquid tumors. ALRN-6924 is currently being evaluated in multiple clinical trials for the treatment of acute myeloid leukemia (AML), advanced myelodysplastic syndrome (MDS) and peripheral T-cell lymphoma (PTCL). For information about its clinical trials, please visit www.clinicaltrials.gov.

On December 11, 2017 Spark Therapeutics (NASDAQ:ONCE), a fully integrated gene therapy company dedicated to challenging the inevitability of genetic disease, and Pfizer Inc. (NYSE:PFE), reported that, with a cumulative follow-up of more than 13 patient years of observation, all 11 participants in the ongoing Phase 1/2 clinical trial of investigational SPK-9001 for the treatment of patients with hemophilia B had discontinued routine infusions of factor IX concentrates and shown sustained steady-state factor IX activity levels with no serious adverse events, thrombotic events or factor IX inhibitors observed (Press release, Pfizer, DEC 11, 2017, View Source [SID1234522561]). Based on individual participant history for the year prior to the study, the overall annualized bleeding rate (ABR) was reduced by 97 percent (calculated based on data after week four; 95 percent based on data after infusion) to a mean of 0.3 (0.5) annual bleeds, compared to a mean of 10.5 bleeds annually before SPK-9001 administration. Overall annualized infusion rate (AIR) was reduced 99 percent (calculated based on data after week four; 97 percent based on data after infusion) to a mean of 0.8 (1.7) annual infusions, compared to a mean of 62.5 infusions per year before SPK-9001 administration. Data on all 11 participants were presented today by Lindsey A. George, M.D., attending physician in the Division of Hematology at Children’s Hospital of Philadelphia and principal investigator of the trial, at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Atlanta.

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"We believe these longer-term data are meeting critical goals of our hemophilia programs," said Katherine A. High, M.D., president and head of research and development at Spark Therapeutics. "Now, with four participants followed for more than 18 months, we continue to see consistent levels of factor IX activity, no serious adverse events, as well as a sustained reduction in both the symptoms of hemophilia and the prophylactic and disease management protocols that were used prior to infusion with SPK-9001."

As of the Nov. 29, 2017 data cutoff, the mean steady-state factor IX activity level at 12 weeks post-administration for the 11 participants was 36 percent of normal (range as of the data cutoff: 15 to 78 percent). As of the data cutoff, the last participant to be infused, who received SPK-9001 manufactured using an enhanced process, was out eight months following SPK-9001 infusion, with a mean factor IX activity level of 60 percent. Spark Therapeutics will enroll up to four additional participants in the current Phase 1/2 clinical trial who will receive SPK-9001 manufactured using an enhanced process to test its comparability to the SPK-9001 received by the first 10 participants enrolled in the ongoing trial.

In this open-label, non-randomized and multicenter Phase 1/2 clinical trial, there were no serious adverse events during or following infusion with SPK-9001, and no participants experienced thrombotic events or developed factor IX inhibitors. Two participants developed an asymptomatic and transient increase in liver enzymes that resolved with a tapering dose of oral corticosteroids. One participant with severe joint disease administered factor for suspected joint bleeding, while a second participant recorded one spontaneous bleed.

About Hemophilia B
Hemophilia, a rare genetic bleeding disorder that causes the blood to take a long time to clot because of a deficiency in one of several blood clotting factors, is almost exclusively found in males. People with hemophilia are at risk for excessive and recurrent bleeding from modest injuries, which have the potential to be life threatening. People with severe hemophilia often bleed spontaneously into their muscles or joints, or rarely into other critical closed spaces such as the intracranial space, where bleeding can be fatal. The incidence of hemophilia B is one in 25,000 male births. People with hemophilia B have a deficiency in clotting factor IX, a specific protein in the blood. Hemophilia B also is called congenital factor IX deficiency or Christmas disease. The current standard of care requires recurrent intravenous infusions of either plasma-derived or recombinant factor IX to control and prevent bleeding episodes. There exists a significant need for novel therapeutics to treat people living with hemophilia.

About the SPK-FIX Program and SPK-9001
SPK-9001 is a novel investigational vector that contains a bio-engineered adeno-associated virus (AAV) capsid and a codon-optimized, high-activity human factor IX gene enabling endogenous production of factor IX.

Spark Therapeutics and Pfizer entered into a collaboration in December 2014 for the SPK-FIX program, including SPK-9001, under which Spark Therapeutics is responsible for conducting all Phase 1/2 studies for any product candidates, while Pfizer will assume responsibility for pivotal studies, any regulatory activities and potential global commercialization of any products that may result from the collaboration.