On December 2, 2018 Magenta Therapeutics (NASDAQ:MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of bone marrow transplant to more patients, reported that the Company presented preclinical research on its targeted conditioning programs at the 60th annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, Magenta Therapeutics, DEC 2, 2018, View Source [SID1234531798]).

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Patients undergoing bone marrow transplant or stem cell gene therapy are first prepared, or conditioned, with non-specific, genotoxic chemotherapy alone or in combination with total body irradiation. This conditioning process is associated with significant toxicity, including development of cancers, infertility, organ toxicities, or even death. As a result, many patients do not consider undergoing a bone marrow transplant or gene therapy. Magenta is developing a portfolio of targeted antibody drug conjugates (ADCs), including non-genotoxic agents, that selectively remove the specific cells to enable a successful transplant or gene therapy procedure.

"This year’s five ASH (Free ASH Whitepaper) data presentations from our portfolio of targeted conditioning programs give further insight into our progress in addressing one of the major challenges of the transplant and gene therapy process: the genotoxic conditioning that leaves patients infertile and puts them at risk for malignancies and organ toxicity," said Michael Cooke, Ph.D., chief scientific officer, Magenta Therapeutics. "Our most advanced targeted conditioning program, C200, is focused on ADCs directed at CD117, a target expressed on stem cells and many types of leukemia cells. Preclinical data at ASH (Free ASH Whitepaper) this year show potent and selective depletion of human and non-human primate stem cells with our non-genotoxic CD117 ADC conjugated to amanitin. In addition, both this ADC and our CD45-targeted ADC from our C100 program demonstrated the additional benefit of anti-leukemia activity and survival advantage in patient-derived leukemia models. Based on these promising data, we are finalizing the CD117 and CD45 ADCs, and we expect to select a lead for development for the CD117 program to launch IND-enabling studies in 2019."

CD117-Amanitin Antibody Drug Conjugates Effectively Deplete Human and Non-Human Primate HSCs: Proof of Concept as a Targeted Strategy for Conditioning Patients for Bone Marrow Transplant, Abstract #3314

Key results, presented by Brad Pearse, Ph.D., Magenta Therapeutics:

An anti-CD117 ADC conjugated with amanitin potently depleted human and non-human primate hematopoietic stem cells and progenitors in vivo.
An anti-CD117 amanitin ADC with engineered fast half-life showed potent stem cell depletion and rapid clearance, providing appropriate pharmacokinetics for patient preparation for bone marrow transplant.
The ADCs were well tolerated at the efficacious doses.
Potent and selective depletion of stem cells with rapid clearance of the ADC could provide a significant improvement over current approaches to patient preparation with an acceptable safety profile prior to BMT for malignancies, autoimmune diseases and gene therapies, broadening patient access to these potentially curative therapies.
Magenta will next finalize the linker-toxin construct and select a lead for development in 2018, then begin IND-enabling studies in 2019.
Single Doses of Antibody Drug Conjugates (ADCs) Targeted to CD117 or CD45 Have Potent In Vivo Anti-Leukemia Activity and Survival Benefit in Patient-Derived AML Models, Abstract #3316

Key results, presented by Jennifer Proctor, Magenta Therapeutics:

CD117 is expressed on human hematopoietic stem and progenitor cells and on leukemia cells in 80% of patients with acute myeloid leukemia (AML) and in 65% of patients with myelodysplastic syndromes (MDS); CD45 is expressed on all lympho-hematopoietic cells and in nearly all blood cancers, other than multiple myeloma.
Both the anti-CD117 amanitin ADC (C200 program) and the anti-CD45 amanitin ADC (C100 program) showed potent killing of human hematopoietic stem cells and human leukemia cell lines expressing these targets in vitro.
A single dose of either ADC showed potent in vivo anti-leukemia activity in mice bearing established human leukemia cell lines.
Both ADCs also significantly improved the survival of mice engrafted with human leukemia cells from AML patients, including leukemias that were resistant to multiple lines of therapy including previous allogeneic bone marrow transplant.
Magenta Therapeutics’ C200 and C100 programs are designed with the dual intent of selectively eliminating the necessary cells to enable a successful transplant and reducing disease burden in patients with active disease or in patients who are at high risk of disease relapse.
Magenta will next finalize the linker-toxin constructs, select anti-CD117 and anti-CD45 leads for development and continue to progress ADC-based conditioning approaches targeting CD45 and CD117 toward clinical development.
Antibody Drug Conjugates Targeted to CD45 or CD117 Enable Allogeneic Hematopoietic Stem Cell Transplantation in Animal Models, Abstract #3324

Key results, presented by Sharon Hyzy, M.S., Magenta Therapeutics:

ADCs targeted to mouse CD45 or mouse CD117 have been shown to effectively condition immunocompetent mice for autologous bone marrow transplant.
To investigate the utility of these murine-specific tool ADCs conjugated to saporin to enable allogenic transplant, Magenta assessed these ADCs as single agents or in combination with immunosuppressive agents to facilitate transplant in a murine allogeneic transplant model.
Both anti-CD45 and anti-CD117 saporin ADCs, when combined with additional immunosuppressants, enabled successful minor mismatch whole bone marrow transplants in mouse models.
Conditioning with the anti-CD45 saporin ADC plus post-transplant cyclophosphamide to prevent graft vs. host disease enabled successful engraftment across minor histocompatibility antigens.
The ADCs were more effective than an unconjugated anti-CD45 antibody, pre-transplant cyclophosphamide, or sublethal irradiation in combination with post-transplant cyclophosphamide.
Magenta will next investigate other linker-toxins as well as ADC-based conditioning in various allogeneic mouse models.
Non-genotoxic conditioning facilitates robust HSPC engraftment and multi-lineage development in a dose dependent manner in Fanconi anemia, Abstract #2041

Key results, presented by Meera Srikanthan, Ph.D., Fred Hutchinson Cancer Research Center:

Conditioning with genotoxic chemotherapy in patients with Fanconi anemia is currently utilized to open the bone marrow niche prior to infusion of hematopoietic stem cells in a bone marrow transplant but is often associated with genotoxic effects.
ADCs targeting hematopoietic stem cells are an emerging non-genotoxic method of conditioning, particularly in diseases associated with DNA damage and cancer predisposition, such as Fanconi anemia.
Researchers at the Fred Hutchinson Cancer Research Center sought to study the application of non-genotoxic ADC-based conditioning targeting hematopoietic stem cells to eliminate leukemogenic host HSCs and to facilitate the engraftment of donor cells.
Results showed that the immunotoxin-based conditioning drugs from Magenta are of similar if not superior efficacy compared to cyclophosphamide, facilitating multi-lineage engraftment of autologous stem cells, as would be used in gene therapy.
Researchers at the Fred Hutchinson Cancer Research Center will next determine whether immunotoxin conditioning facilitates engraftment of gene-modified stem cells using FancA (-/-) mice and optimize dosing of immunotoxin platform to completely eliminate host hematopoiesis in order to decrease the risk of leukemogenesis.
Targeting CD45 with an Amanitin Antibody-Drug Conjugate Effectively Depletes Human HSCs and Immune Cells for Transplant Conditioning, Abstract #4526

Key results will be presented by Rahul Palchaudhuri, Ph.D., Magenta Therapeutics, on Monday, December 3, 2018.

A human/primate cross-reactive anti-CD45 amanitin ADC potently depletes human hematopoietic stem cells and immune cells in culture.
The anti-CD45 ADC achieved efficient depletion of immune cells in the periphery and hematopoietic stem cells in the bone marrow of humanized mice.
Simultaneous depletion of immune and hematopoietic stem cells using an anti-CD45 ADC may enable safer conditioning for allogeneic transplant and enable immune-reset in autoimmune disease transplantation.
Magenta plans to optimize the anti-CD45 ADC and select a development candidate in 2019, with IND-enabling studies to begin in 2020.

On December 2, 2018 Celgene Corporation (NASDAQ: CELG) reported initial data from the dose-escalation part of an ongoing, open-label multicenter phase 1/2 study of investigational lisocabtagene maraleucel (liso-cel; JCAR017) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), including patients with cytogenetic features of high-risk disease, who were previously treated with ibrutinib (Press release, Celgene, DEC 2, 2018, View Source [SID1234531784]). The data were presented by Tanya Siddiqi, M.D. in an oral presentation at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, C.A. (Abstract #300).

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Data presented today from TRANSCEND CLL-004 include 16 patients from the ongoing phase 1 monotherapy dose-escalation part of the study. The median number of lines of prior therapy was 4.5, and 75% of patients had high-risk cytogenetic features. All patients had previously received treatment with ibrutinib, 81% had relapse/refractory disease on ibrutinib and 50% received prior treatment with ibrutinib and venetoclax. Following lymphodepletion with fludarabine (30 mg/m2) and cyclophosphamide (300 mg/m2) for three days, patients received liso-cel at dose level 1 (5×107 CAR+ T cells) or dose level 2 (1×108 CAR+ T cells).

The overall response rate (ORR), which was an exploratory objective, was 81%, with 43% of patients demonstrating a complete response (CR). As of September 2018, five patients have six-month follow-up and all have maintained a response and undetectable minimal residual disease (uMRD) in the blood as measured by flow cytometry (10-4). The median time-to-peak expansion was 16 days, and CAR+ T cells remained detectable in patients at three months.

"Ibrutinib is a standard of care for patients with CLL, but outcomes are poor for patients whose disease progresses on or after ibrutinib," said Alise Reicin, M.D., President, Global Clinical Development for Celgene. "These initial findings support further research with liso-cel in CLL and reinforce Celgene’s commitment to cellular therapy across a broad spectrum of blood cancers."

The most common treatment-emergent adverse events reported included anemia (88%), thrombocytopenia (81%), cytokine release syndrome (75%), neutropenia (63%), leukopenia (56%), hypokalemia (50%), pyrexia (38%), lymphopenia (31%), nausea (31%), diarrhea (25%), febrile neutropenia (25%), headache (25%), insomnia (25%), and tremor (25%). One patient (6.3%) experienced grade 3 cytokine release syndrome and three patients (18.8%) experienced grade 3 neurologic events. No patients experienced grade 4 cytokine release syndrome or neurologic events.

"In CLL, undetectable MRD correlates with improved outcomes for patients and is particularly difficult to achieve in patients who have progressed on ibrutinib," said lead study investigator Tanya Siddiqi, M.D., City of Hope National Medical Center. "The high response rates we observed in heavily pretreated patients in this initial data set, along with undetectable MRD status, that appears to be maintained over time, warrants further investigation of liso-cel in this area of high unmet need."

Liso-cel is not approved in any country.

About Liso-cel

Liso-cel is an investigational defined composition CD19-directed CAR T cell product candidate using a 4-1BB costimulatory domain. Celgene’s lead CAR T trial, TRANSCEND NHL-001, is studying liso-cel in adult patients with relapsed or refractory diffuse large B cell lymphoma, primary mediastinal B-cell lymphoma, follicular lymphoma Grade 3B, and mantle cell lymphoma.

On December 2, 2018 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company focused on the development of precision medicines for oncology, reported preliminary data in angioimmunoblastic T-cell lymphoma (AITL) and CXCL12+ peripheral T-cell lymphoma (PTCL), the two expansion cohorts in its Phase 2 clinical trial of its lead drug candidate tipifarnib in patients with relapsed or refractory PTCL (Press release, Kura Oncology, DEC 2, 2018, View Source [SID1234531800]).

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The data, presented today at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, showed encouraging activity with tipifarnib in late-stage PTCL patients, including a significant association between CXCL12 expression and clinical benefit, and proof of concept in AITL, an aggressive form of T-cell lymphoma often characterized by high levels of CXCL12 expression. A copy of the poster is available on the Company’s website at www.kuraoncology.com.

"The mechanism of action of farnesyl transferase inhibitors has remained elusive for several decades," said Antonio Gualberto, M.D., Ph.D., Head of Development and Chief Medical Officer of Kura Oncology. "Our initial data in HRAS mutant head and neck cancer provided strong evidence of activity in tumors driven by this oncogene. However, many other tumors such as T- and B-cell lymphomas, myeloid leukemias, pancreatic or breast cancers, in which anecdotal evidence of tipifarnib activity has been reported, do not usually carry HRAS mutations. We believe the preliminary results reported at ASH (Free ASH Whitepaper) validate our observation that the CXCL12 pathway is a therapeutic target of tipifarnib and provide a potential path to expand the development of tipifarnib well beyond HRAS mutant solid tumors by using CXCL12-related biomarkers to enrich for patients most likely to benefit from treatment. We will continue our efforts to identify these patient subsets and to bring this important drug candidate to patients in need."

As of November 21, 2018, a total of 39 patients were enrolled in the ongoing Phase 2 trial, including 19 patients with AITL (16 patients in the AITL extension cohort and 3 patients in the previous portion of the study). Six of the 16 AITL patients were not evaluable as of the data cutoff date, including two who were pending initial efficacy assessments. Of the 13 evaluable AITL patients, two achieved a complete response (CR) and four achieved a partial response (PR), for an objective response rate (ORR) of 46% (six of 13). According to the study protocol, the AITL cohort is considered positive when four or more responses are observed.

The study also identified a particularly responsive subset within AITL and non-AITL patients. Specifically, patients with a high ratio of expression of CXCL12 to its receptor CXCR4 experienced a 50% ORR (five of 10) and a 90% clinical benefit rate (nine of 10 with either complete response, partial response or stable disease) with tipifarnib. Patients in this Phase 2 trial had a median of three prior lines of therapy (range 1-7). The high CXCL12/CXCR4 expression ratio had 90% sensitivity and 93% specificity to identify PTCL patients likely to benefit from tipifarnib.

In addition to the Phase 2 clinical data, the results from two ancillary, non-clinical studies were also reported at ASH (Free ASH Whitepaper). In the first, the expression of CXCL12 and CXCR4 was investigated using tumor bank samples of PTCL patients treated with standard-of-care agents. Worse prognosis was observed in PTCL patients with high CXCL12/CXCR4 expression ratio, indicating that CXCL12 is a negative prognostic factor for standard PTCL therapy. In the second study, the effect of the incubation of stroma cells with tipifarnib on CXCL12 secretion was investigated in a mouse model of bone marrow culture. Tipifarnib reduced secretion of the CXCL12 chemokine from the stromal cells, providing a potential mechanism of action for the observed clinical activity.

"To our knowledge, these results position tipifarnib as the first CXCL12 inhibitor with reported proof-of-concept data, marking a significant advancement in our development strategy," said Troy Wilson, Ph.D., President and CEO of Kura Oncology. "Our data suggest that as many as 40% of PTCL patients express high CXCL12. In addition, the discovery of CXCL12-related biomarkers offers the potential to increase the opportunity for tipifarnib into other hematological and solid tumor indications. We intend to explore those indications while continuing to gather additional data from our ongoing Phase 2 study and expect to provide an update at a medical meeting next year."

The Phase 2 study was designed to investigate the anti-tumor activity of tipifarnib in patients with relapsed or refractory PTCL. After preliminary data suggested that CXCL12 expression was associated with tipifarnib’s clinical activity, two expansion cohorts were added to enroll patients with tumors expected to overexpress CXCL12: AITL tumors, and those non-AITL tumors that lack a single nucleotide variation in the 3’-untranslated region (3′-UTR) of the CXCL12 gene (CXCL12+ PTCL). CXCL12 is a stroma-derived chemokine that promotes the progression of lymphoma and other hematological and solid tumors carrying the CXCR4 receptor, and our previous results had suggested an association between CXCL12 expression and the most common form of the 3’-UTR CXCL12 variant. In the expansion cohorts, both the presence or absence of this variant and the expression levels of CXCL12 and CXCR4 were assessed.

In the expansion cohorts in the Phase 2 trial tipifarnib was dosed at 300 mg twice daily on days 1-21 of a 28-day cycle. The reported data indicated that tipifarnib was generally well-tolerated, with adverse events consistent with its known safety profile. The most common treatment-related adverse events (grade ≥ 3) were hematology-related, including neutropenia, thrombocytopenia, leukopenia, febrile neutropenia and anemia.

Last week, the U.S. Patent and Trademark Office (USPTO) issued a new patent for tipifarnib as a method of treating patients with AITL. In May 2018, the USPTO issued a patent for tipifarnib as a method of treating patients with certain CXCL12-expressing cancers, including PTCL. Both patents expand protection for tipifarnib, providing exclusivity in the U.S. to 2037.

Webcast Information

Kura’s management will host a webcast at 11:30 p.m. ET / 8:30 p.m. PT today, December 2, 2018, following the conclusion of the poster presentation at the ASH (Free ASH Whitepaper) 2018 Annual Meeting. The live audio webcast and slides of the presentation will be available from the Investors and Media section of the company website at www.kuraoncology.com, and will be archived there for 30 days.

About Tipifarnib

Kura Oncology’s lead drug candidate, tipifarnib, is a potent and highly selective inhibitor of farnesylation, a key cell signaling process implicated in cancer initiation and development. Tipifarnib was previously studied in more than 5,000 cancer patients and showed compelling and durable anti-cancer activity in certain patient subsets, however no molecular mechanism of action had previously been determined that could explain its activity across a range of diverse clinical indications, including squamous tumors that carry mutant HRAS, as well as in lymphoid, myeloid and solid tumors that do not carry HRAS mutations. Leveraging advances in next-generation sequencing as well as emerging information about cancer genetics and tumor biology, Kura is seeking to identify those patients most likely to benefit from tipifarnib. In November 2018, Kura initiated its first global, registration-directed trial of tipifarnib in patients with recurrent or metastatic HRAS mutant HNSCC

On December 2, 2018 Immune Design (Nasdaq: IMDZ), an immunotherapy company focused on next-generation therapies in oncology, reported long-term follow up results from a randomized Phase 2 clinical trial of 10 ug intratumoral G100, a TLR4 agonist, with or without pembrolizumab, in follicular lymphoma patients (Press release, Immune Design, DEC 2, 2018, View Source [SID1234531785]).

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In the 26 naïve and relapsed/refractory patients in the randomized trial, the data continue to support the clinical activity of G100, with overall response rates of 46% and 23% in patients receiving a G100 regimen that includes low-dose radiation, with or without pembrolizumab, respectively. Also, disease control was shown in 92% and 85% of patients treated with the G100 regimen with or without pembrolizumab, respectively. In addition, responses appeared to be durable, with overall progression free survival at 11.1 or 7.4 months in patients treated with the G100 regimen with or without pembrolizumab, respectively. The data were presented today at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in San Diego.

"Follicular lymphoma continues to be a difficult-to-treat malignancy, particularly in the relapsed setting, and to date immunotherapy has not been successful and the current standard of care is associated with a number of serious adverse events," said Carlos Paya, M.D., chief executive officer of Immune Design. "We are encouraged by the potential for lymphoma patients with G100, a first in class immuno-modulatory agent that leads to systemic anti-lymphoma benefit when injected intratumorally. The high response rates, favorable durability and excellent safety profile we’re seeing for G100 has prompted us to embark on a potentially pivotal clinical trial in the relapsed refractory setting, as well as pursue additional trials in earlier lines of therapy in follicular lymphoma and other malignancies."

Additional data presented in the poster:

Increases in immunogenicity markers of CD8+ T-cells and CD8/CD4 ratio in the tumor microenvironment correlated with clinical response (p= .0858 and .0357 respectively). Similarly, a decrease in C20-expressing tumor cells correlated with improved clinical outcomes (p=.0221).

G100 was well tolerated and the combination with pembrolizumab did not cause unexpected or worsening toxicity.
About G100

G100 is Immune Design’s lead product candidate and contains a potent synthetic small molecule toll-like receptor-4 (TLR-4) agonist called Glucopyranosyl Lipid A (GLA). G100 activates innate and adaptive immunity in the tumor microenvironment to generate an immune response against the tumor’s pre-existing diverse set of antigens. A growing set of clinical and preclinical data have demonstrated the ability of G100 to activate tumor-infiltrating lymphocytes, macrophages and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor. The induction of local and systemic immune responses has been shown to result in local and abscopal (shrinking of tumors outside the scope of the localized treatment) tumor control. G100 is currently in development to treat patients with relapsed follicular lymphoma (FL), a sub-type of Non-Hodgkin lymphoma. Immune Design intends to start a study in earlier-stage lymphoma patients in combination with rituximab, a standard treatment for lymphomas, and is evaluating studies in other B-cell malignancies beyond FL, as well as potential solid tumor indications.

On December 2, 2018 Celgene Corporation (NASDAQ: CELG) and Acceleron Pharma Inc. (NASDAQ: XLRN) reported results from the pivotal, phase 3 MEDALIST trial evaluating the efficacy and safety of investigational luspatercept to treat patients with ring sideroblast (RS+) myelodysplastic syndromes (MDS)-associated anemia who require red blood cell transfusions and who had failed, were intolerant to, or ineligible for erythropoietin therapy (Press release, Celgene, DEC 2, 2018, View Source [SID1234531801]). Results were presented by Alan F. List, M.D. during the Plenary Scientific Session at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, C.A. (Abstract #1).

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"Severe anemia resulting in red blood cell transfusion dependence is a significant challenge for patients with low- and intermediate-risk MDS. Those who become resistant or refractory to currently available treatments have limited alternatives," said Dr. List, President and CEO of Moffitt Cancer Center. "The findings from MEDALIST are very exciting as they support the hypothesis that targeting red blood cell precursor maturation could help to address patients’ anemia and allow them to achieve transfusion independence."

MEDALIST met the primary endpoint of red blood cell transfusion independence (RBC-TI) for 8 or more weeks during the first 24 weeks of the study. Treatment with luspatercept resulted in a statistically significantly greater proportion of patients achieving RBC-TI ≥ 8 weeks compared to placebo. The study also found in secondary endpoints that treatment with luspatercept resulted in a statistically significant higher percentage of patients achieving RBC-TI of 12 or more weeks in the first 24 or 48 weeks of the study, as well as hematologic improvement-erythroid (HI-E) of 8 or more weeks.

Endpoints Luspatercept Placebo P-Value
RBC-TI ≥8 weeks (weeks 1-24) 37.9 % (58/153) 13.2 % (10/76) < 0.0001
RBC-TI ≥12 weeks (weeks 1-24) 28.1 % (43/153) 7.9 % (6/76) 0.0002
RBC-TI ≥12 weeks (weeks 1-48) 33.3 % (51/153) 11.8 % (9/76) 0.0003
HI-E ≥ 8 weeks (IWG 2006, weeks 1-24) 52.9 % (81/153) 11.8 % (9/76) < 0.0001

MEDALIST Safety Summary

Treatment-emergent adverse events (TEAEs) of Grade 3 or 4 were reported in 42.5% (65/153) of patients receiving luspatercept and 44.7% (34/76) of patients receiving placebo. Progression to acute myeloid leukemia (AML) occurred in four patients, three patients (2.0%) receiving luspatercept and one patient (1.3%) receiving placebo. Five patients receiving luspatercept (3.3%) and four patients receiving placebo (5.3%) experienced one or more TEAE that resulted in death.

Most common TEAEs of any Grade in Greater than 10% of Patients in Either Arm

Luspatercept
N=153

Placebo
N=76

Fatigue 26.8 % 13.2 %
Diarrhea 22.2 % 9.2 %
Asthenia 20.3 % 11.8 %
Nausea 20.3 % 7.9 %
Dizziness 19.6 % 5.3 %
Back pain 19.0 % 6.6 %

"The MEDALIST results demonstrate the potential clinical benefit of luspatercept in achieving red blood cell transfusion independence in patients with low-to-intermediate risk RS+ MDS, an area in need of new treatments," said Alise Reicin, MD, President, Global Clinical Development for Celgene. "Based on these results, we are encouraged that this first-in-class erythroid maturation agent may help these patients address the underlying cause of their disease-related chronic anemia."

"It’s truly an honor to showcase the results from the MEDALIST trial as the first presentation of the ASH (Free ASH Whitepaper) Plenary Session," said Habib Dable, President and Chief Executive Officer of Acceleron. "The results from the MEDALIST trial increase our confidence in the potential of luspatercept to provide a meaningful treatment option for patients suffering from lower-risk RS+ MDS worldwide. We’re excited to continue our clinical development program in MDS, beta-thalassemia, and myelofibrosis, while also exploring additional applications for luspatercept in a range of diseases associated with anemia."

Luspatercept is not approved in any region for any indication. The companies are planning regulatory application submissions of luspatercept in the United States and Europe in the first half of 2019.

About MEDALIST

MEDALIST is a phase 3, randomized, double blind, placebo-controlled, multi-center study evaluating the safety and efficacy of luspatercept in patients with very low-, low-, or intermediate-risk non-del(5q) myelodysplastic syndromes (MDS). All patients were RBC transfusion dependent and were either refractory or intolerant to prior erythropoiesis-stimulating agent (ESA) therapy, or were ESA naïve with endogenous serum erythropoietin ≥ 200 U/L, and had no prior treatment with disease modifying agents. The median age of the patients enrolled in the trial was 71 years in the luspatercept treatment group and 72 years in the placebo group. Median transfusion burden in both treatment arms was 5 RBC units/8 weeks. 229 patients were randomized to receive either luspatercept 1.0 mg/kg (153 patients) or placebo (76 patients) via subcutaneous injection once every 21 days. The study was conducted at 65 sites in 11 countries.

About Luspatercept

Luspatercept is a first-in-class erythroid maturation agent (EMA) that is believed to regulate late-stage red blood cell maturation. Acceleron and Celgene are jointly developing luspatercept as part of a global collaboration. Phase 3 clinical trials continue to evaluate the safety and efficacy of luspatercept in patients with MDS (the MEDALIST trial) and in patients with beta-thalassemia (the BELIEVE trial). The COMMANDS phase 3 trial in first-line, lower-risk, MDS patients, the BEYOND phase 2 trial in non-transfusion-dependent beta-thalassemia, and a phase 2 trial in myelofibrosis are ongoing. For more information, please visit www.clinicaltrials.gov.