On December 11, 2017 Celgene Corporation (NASDAQ: CELG) and bluebird bio, Inc. (Nasdaq: BLUE) reported that updated results from the ongoing CRB-401 Phase 1 clinical study of bb2121, an investigational anti-B-cell maturation antigen (BCMA) CAR T cell therapy, in 21 patients with late-stage relapsed/refractory multiple myeloma will be presented in an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, Georgia (Press release, bluebird bio, DEC 11, 2017, View Source [SID1234522486]).

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The objective of this Phase 1 dose-escalation study is to evaluate safety and efficacy of bb2121 and determine a recommended Phase 2 dose.

"Celgene has a longstanding commitment to patients with multiple myeloma through our extensive research efforts in this deadly blood cancer," said Nadim Ahmed, President, Hematology and Oncology for Celgene. "Looking ahead, we see BCMA as an important target in this disease and we believe bb2121 has the potential to create significant impact on the treatment approach and outcomes for these patients."

"The growing body of bb2121 clinical data are building a compelling story, further supporting the importance of the therapy’s unique features," said Dave Davidson, M.D., chief medical officer, bluebird bio. "The responses achieved in this relapsed and refractory patient population, combined with the generally tolerable safety profile, reinforce the potential role of bb2121 as a groundbreaking CAR T therapy in multiple myeloma."

Durable clinical responses in heavily pretreated patients with relapsed/refractory multiple myeloma: Updated results from a multicenter study of bb2121 anti-BCMA CAR T cell therapy (Abstract #740)

Presenter: James Kochenderfer, M.D., the Center for Cancer Research at the National Cancer Institute in Bethesda, Maryland

Date: Monday, December 11, 3:00 pm (Oral presentation)
Location: Hall C1 (Georgia World Congress Center)

Session Title: Myeloma: Therapy, excluding Transplantation I

The open-label Phase 1 CRB-401 study (NCT02658929) is evaluating the preliminary safety and efficacy of bb2121 anti-BCMA CAR T cell in patients with relapsed and/or refractory multiple myeloma. The study also evaluated the recommended dose of bb2121 for future studies.

Patients on study were heavily pre-treated, with a median of 7 prior therapies (range: 3 – 14):

100% previously treated with lenalidomide and bortezomib
91% previously treated with pomalidomide and carfilzomib
71% previously treated with daratumumab
29% of patients were penta-refractory (bortezomib, lenalidomide, carfilzomib, pomalidomide, daratumumab)
All patients had at least one prior autologous stem cell transplant (ASCT).
As of the October 2, 2017 data cut-off, 21 patients had been enrolled and dosed in the dose-escalation phase of the study, in four dose cohorts: 50 x 106, 150 x 106, 450 x 106 and 800 x 106 CAR+ T cells. This multi-center study has enrolled patients at nine sites in the U.S with central manufacturing performed at Celgene.
Patients received a conditioning regimen of cyclophosphamide and fludarabine, followed by an infusion of bb2121 anti-BCMA CAR T cells. The CAR T cells were produced from each patient’s own blood cells, which were modified using a proprietary lentiviral vector encoding the anti-BCMA CAR.

Results in the active dose cohorts (150 x 106, 450 x 106 and 800 x 106 CAR+ T cells; N=18) were:

Median follow-up was 40 weeks (range: 6.6-69)
17/18 (94%) patients achieved an objective response
16/18 (89%) patients achieved at least a very good partial response (VGPR)
10/18 (56%) patients achieved a complete response (CR, N = 7), or unconfirmed complete response (N = 3)
9 of 10 patients who were evaluable for MRD status were found to be MRD-negative
Median PFS has not been reached in the active dose cohorts. The PFS at 6 months and 9 months was 81% and 71%, respectively.
Three patients in the dose-escalation who responded to therapy subsequently experienced disease progression.
In the dose-escalation phase, 15/21 (71%) of patients had cytokine release syndrome (CRS), mostly Grade 1 & 2, with 2 patients experiencing Grade 3 CRS (9%). Four patients received tocilizumab, 1 (Grade 2 CRS) received steroids and in each case the CRS resolved within 24 hours. The most common treatment-emergent Grade 3-4 AEs in 21 infused patients were cytopenias commonly associated with lymphodepleting chemotherapy including neutropenia (86%), anemia (57%) and thrombocytopenia (43%). There were two deaths in the active cohorts at 22 and 69 weeks following infusion, respectively. The first was due to cardiac arrest and the second was due to myelodysplastic syndrome; both subjects were in a myeloma CR at their last study assessment prior to death. Based on the findings during dose escalation, a dose expansion phase of 12 subjects has started testing doses between 150-450 x 106 CAR+ T cells. In the dose expansion phase, one patient treated at the 450 x 106 CAR+ T cells dose experienced Grade 4 neurotoxicity including focal cerebral edema and subarachnoid hemorrhage. This patient had a high tumor burden, and a history of subarachnoid hemorrhage. The event was successfully managed, and the patient remains in the response group. No other Grade 3/4 neurotoxicity was observed in the escalation or expansion cohort.

"To see these types of responses after one treatment with bb2121 in a heavily pre-treated patient population is very promising, and we are hopeful that CAR T therapy with bb2121 may become an important therapy in the fight against multiple myeloma, which remains an insidious and incurable disease," said James Kochenderfer, M.D., the Center for Cancer Research at the National Cancer Institute in Bethesda, Maryland and a primary investigator in the study."

bb2121 is an investigational compound that is not approved for any use in any country. bb2121 recently received Breakthrough Therapy Designation from the U.S. FDA and PRIME eligibility from the EMA. Celgene has also sponsored an open-label, single-arm phase 2 study (KarMMa), which is open to recruitment, to evaluate bb2121 further in patients with relapsed/refractory multiple myeloma. (NCT03361748)

About Celgene

Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through next-generation solutions in protein homeostasis, immuno-oncology, epigenetics, immunology and neuro-inflammation. For more information, please visit www.celgene.com. Follow Celgene on Social Media: @Celgene, Pinterest, LinkedIn, Facebook and YouTube.

On December 10, 2017 Agios Pharmaceuticals, Inc. (Nasdaq:AGIO) reported updated data today from its wholly owned pyruvate kinase-R (PKR) activator, AG-348, demonstrating its potential as the first disease-modifying treatment for patients with pyruvate kinase (PK) deficiency at the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Agios Pharmaceuticals, DEC 10, 2017, View Source [SID1234522569]). PK deficiency is a rare, potentially debilitating, congenital anemia.

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DRIVE PK is an ongoing global open-label, Phase 2, safety and efficacy trial evaluating AG-348 in 52 adult, transfusion-independent patients with PK deficiency. As of the July 14, 2017 data cut-off 43 patients had completed the six-month core dosing period and 9 patients discontinued treatment during the core dosing period. Of the 52 patients enrolled, 26 (50%) experienced a maximum hemoglobin (Hb) increase from baseline of >1.0 gram per deciliter (g/dL) during the six-month core period. For the 42 patients enrolled with at least 1 missense mutation, 25 (60%) experienced a maximum Hb increase from baseline of >1.0 g/dL. AG-348 remains well-tolerated with the majority of adverse events (AEs) being Grade 1 or 2. The median treatment duration was 37.5 weeks, with a maximum of 92.4 weeks.

"With some patients approaching two years of treatment, we are encouraged that AG-348 continues to be well-tolerated and demonstrates clinically relevant, sustained increases in hemoglobin in adults with PK deficiency," said Rachael Grace, M.D., of the Dana-Farber Boston Children’s Cancer and Blood Disorder Center and a principal investigator for the study. "AG-348 has the potential to be the first therapy for patients with PK deficiency that targets the underlying cause of this chronic anemia and its associated complications."

Patients in DRIVE PK were randomized to a starting dose of 50 mg or 300 mg twice daily, treated for six months in a core treatment period and then offered treatment in an extension period. Enrollment was completed in November 2016 with 52 patients. Nine subjects discontinued during the core treatment period. Thirty-six of 43 patients who completed the six month core treatment period entered the extension period. As of the data cut-off, 29 patients remain on treatment in the extension period.

"DRIVE PK has established a clear signal of activity for AG-348 in PK deficiency and was instrumental in informing the design of the pivotal program we are on track to initiate in the first half of 2018," said Chris Bowden, M.D., chief medical officer at Agios. "In addition to this clinical work, our planned global PKD patient registry will complement our patient finding efforts and further advance our understanding of the disease burden for this rare anemia."

Safety Data

A safety analysis conducted for all 52 treated patients as of the data cut-off shows that AG-348 continues to be well tolerated.

The majority of treatment-related AEs were Grade 1-2; the most frequent were headache, insomnia and nausea.
As previously reported, four patients experienced treatment-related AEs leading to discontinuation: pleural effusion (n=1), hypertriglyceridemia (n=1), pharyngitis/nausea (n=1) and anemia (n=1).
As previously reported, four patients experienced treatment-related serious adverse events: withdrawal hemolysis followed by anemia (n=1), anemia (n=1), osteoporosis (n=1) and hypertriglyceridemia (n=1).
A previously reported case of drug-related pharyngitis (n=1) was subsequently deemed unrelated to study drug.
Measurements of hormone levels in men at doses ≤50 mg BID suggest mild aromatase inhibition by AG-348; ongoing follow-up will continue to assess potential clinical significance.
Efficacy Data

In the efficacy analysis 26 of 52 patients (50%) overall and 25 of 42 patients (60%) with at least one missense mutation achieved rapid and sustained Hb increases from baseline of >1.0 g/dL as of the data cut-off.

In patients who had Hb increases of >1.0 g/dL, the mean maximum Hb increase was 3.4 g/dL (range 1.1-5.8 g/dL).
The median time to first Hb increase of >1.0 g/dL was 10 days (range 7–187 days).
As previously reported, the median baseline Hb in patients who experienced a maximum Hb increase of >1.0 g/dL was 9.7 g/dL (range 7.3–12.3 g/dL) vs. 8.0 g/dL (range 6.5–10.1 g/dL) in patients who did not experience the increase.
Pivotal Development Plan

Agios plans to initiate two global, pivotal trials in adults with PK deficiency in the first half of 2018 based on transfusion status:

A randomized, placebo-controlled trial with a 1:1 randomization known as ACTIVATE is expected to enroll approximately 80 patients who do not receive regular transfusions. The primary endpoint of the trial is the proportion of patients who achieve a sustained hemoglobin increase ≥1.5 g/dL.
A single arm trial of approximately 20 regularly transfused patients known as ACTIVATE-T will have a primary endpoint of reduction in transfusion burden over six months.
About Pyruvate Kinase Deficiency and Genetic Background

PK deficiency is a rare inherited disease that presents as hemolytic anemia, which is the accelerated destruction of red blood cells. The inherited mutations in PKR enzymes cause a deficit in cellular energy within the red blood cell, as evidenced by lower pyruvate kinase enzyme activity and a decline in ATP (adenosine triphosphate) levels and a build-up of upstream metabolites, including 2,3-DPG (2,3-diphosphoglycerate).

The current standard of care for PK deficiency is supportive, including blood transfusions, splenectomy, chelation therapy to address iron overload and/or interventions for other treatment- and disease-related morbidities. There is no approved therapy to treat the underlying cause of PK deficiency.

PK deficiency is an autosomal recessive disease whereby all patients inherit two mutations, one from each parent. More than 250 different mutations have been identified to date. The mutations observed in PK deficiency patients are classified in two main categories. A missense mutation causes a single amino acid change in the protein, generally resulting in some functional protein. A non-missense mutation is any mutation other than a missense mutation, generally resulting in little functional protein. It is estimated that 58 percent of patients with PK deficiency have two missense mutations, 27 percent have one missense and one non-missense mutation, and 15 percent have two non-missense mutations1.

Boston Children’s Hospital, in collaboration with Agios, is conducting a Natural History Study to better understand the symptoms and complications of PK deficiency, identify patients and treatment centers, and capture other clinical data, including quality of life measures and genetic information.

On December 10, 2017 bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies for cancer, reported data from two studies of its LentiGlobin gene therapy product candidate in patients with transfusion-dependent β-thalassemia (TDT) (Press release, bluebird bio, DEC 10, 2017, View Source [SID1234522484]). Data from the Northstar (HGB-204) and Northstar-2 (HGB-207) studies were presented today at the 59th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) by Janet Kwiatkowski, M.D., MSCE, of Children’s Hospital of Philadelphia, and Mark C. Walters, M.D., of UCSF Benioff Children’s Hospital, respectively.

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"Addressing the underlying genetic cause of TDT to restore production of functional hemoglobin can potentially eliminate or reduce the need for chronic blood transfusions in people with this disease, which we expect will reduce the risk of iron overload and associated long-term complications of TDT, and may allow cessation of chelation therapy," said Dave Davidson, chief medical officer, bluebird bio. "Northstar-2 is the first clinical trial to use our refined manufacturing process for LentiGlobin drug product. Early data from this study demonstrates consistently higher in vivo vector copy numbers and HbAT87Q hemoglobin levels, potentially enabling patients to consistently achieve near-normal or normal total hemoglobin levels. It is important to demonstrate the long-term benefit of gene therapy, and follow-up data of up to three years from the first Northstar study show that nearly all patients with non-β0/β0 genotypes were transfusion-free. We are engaged with the regulatory authorities in the context of the Breakthrough Designation from FDA, and PRIME and Adaptive Pathways from EMA, and look forward to submitting these data to seek marketing approval for LentiGlobin in TDT."

"People with transfusion-dependent thalassemia need regular blood transfusions to survive, but chronic transfusions lead to unavoidable iron overload that can result in multi-organ damage and shortened life span. Eliminating or reducing the need for transfusions can reduce the risk of these long-term complications," said Janet L. Kwiatkowski, MD, MSCE, Director of the Thalassemia Program at the Children’s Hospital of Philadelphia and Associate Professor of Pediatrics at the Perelman School of Medicine of the University of Pennsylvania, and a primary investigator of the Northstar and Northstar-2 studies. "The growing body of data from the Northstar studies indicate LentiGlobin gene therapy may enable transfusion independence for the majority of patients with non-β0/β0 genotypes – and that this effect has been durable during the 3 years of follow-up."

Clinical Outcomes up to 3 Years Following LentiGlobin Gene Therapy for Transfusion-Dependent β-Thalassemia in the Northstar HGB-204 Study (Oral Abstract #360)
Presenter: Janet Kwiatkowski, M.D., MSCE, Children’s Hospital of Philadelphia, Philadelphia, PA
Date and Time: Sunday, December 10 at 10:45 a.m.
Location: Building B, Level 2, B213-B214

The Northstar study is an open-label, single-dose, international, multi-center Phase 1/2 study designed to evaluate the efficacy and safety of LentiGlobin for the treatment of patients with TDT. The study has completed its treatment phase and 18 patients with TDT (eight with β0/β0 and 10 with non-β0/β0 genotypes) received LentiGlobin drug product (DP). Results as of September 21, 2017 include:

All 18 patients have ≥18 months follow up, with 10 completing two-year analysis. Three patients have three years of follow up (median follow-up: 27.4 months; min-max: 17.5-36.5 months).
Nine of ten patients with non-β0/β0 genotypes were free from chronic transfusions for a median of 29 months (range: 14.7-33.1 months).
Patients with non-β0/β0 genotypes who were able to achieve freedom from chronic transfusions had HbAT87Q concentrations of 3.6-9.3.
The one patient with a non-β0/β0 genotype who still required periodic transfusions was treated with LentiGlobin with a VCN in the lower range (VCN: 0.3 copies/diploid genome).
Two of eight patients with β0/β0 genotypes have not received a transfusion in more than a year (16.7 months and 15.7 months). At the patients’ last study visits (Month 36 and Month 18, respectively), total hemoglobin levels were 10.2 and 10.3 g/dL and HbAT87Q levels were 9.7 and 7.0 g/dL, respectively.
Clinically meaningful reductions in transfusion volume and frequency were observed in five of the six patients with β0/β0 genotypes who have continued to receive transfusions.
For the 18 study participants, the median DP vector copy number (VCN) was 0.7 (range: 0.3-1.5) copies/diploid genome, the median cell dose was 8.1 (range: 5.2-18.1) x 106 CD34+ cells/kg, and the proportion of transduced CD34+ cells was 17-58 percent.
The safety profile of LentiGlobin DP continues to be consistent with myeloablative conditioning with single-agent busulfan. No Grade 3 or higher DP-related adverse events (AEs) have been observed, and there is no evidence of clonal dominance.
All study participants remain enrolled in the trial, and there have been no reports of graft versus host disease (GVHD).
Results from the HGB-207 (Northstar-2) Trial: A Phase 3 Study to Evaluate Safety and Efficacy of LentiGlobin Gene Therapy for Transfusion-Dependent β-thalassemia (TDT) in Patients with non-β0/β0 Genotypes (Oral Abstract #526)
Presenter: Mark C. Walters, M.D., UCSF Benioff Children’s Hospital, Oakland, Calif.

Date and Time: Sunday, December 10 at 5:15 p.m.
Location: Building C, Level 1, C101 Auditorium

The Northstar-2 study is an ongoing, open-label, single-dose, international, multicenter Phase 3 study designed to evaluate the efficacy and safety of LentiGlobin for the treatment of patients with TDT and non-β0/β0 genotypes. As of December 1, 2017, drug product had been manufactured for 10 patients. The median LentiGlobin DP VCN these patients received was 3.3 (range: 2.4-5.4) copies/diploid genome) compared to a median DP VCN of 0.7 (range: 0.3-1.5) copies/diploid genome in the Phase 1/2 Northstar study. Results in treated patients, ages 15 to 24 years, include:

Seven patients had been infused with LentiGlobin as of October 13, 2017. The median follow-up was 3 months (range: 1-9 months).
All three patients who have ≥6 months follow-up are transfusion-free, and 2/3 have achieved or are approaching a normal total hemoglobin level (up to 12.5 g/dl total Hb; range in three patients: 8.4 – 12.5) without transfusions (up to 10.2 g/dL vector-derived HbAT87Q).
Five of six patients treated in the study with ≥3 months follow-up data available as of December 1, 2017 are making at least 6 g/dL of HbAT87Q.
The safety profile of LentiGlobin to date is similar to that observed in the Northstar study, and consistent with myeloablative conditioning with single-agent busulfan. No DP-related AEs have been observed.
All study participants remain enrolled in the trial, and there have been no reports of graft failure or graft versus host disease (GVHD).
Webcast Information
bluebird bio will host a webcast at 8:30 p.m. ET on Sunday, December 10, 2017. The webcast can be accessed under "Calendar of Events" in the Investors and Media section of the company’s website at www.bluebirdbio.com.

About TDT
Transfusion-dependent β-thalassemia (TDT) is a severe genetic disease characterized by reduced or absent hemoglobin levels that results in severe anemia and ineffective red blood cell production. Supportive care for people with TDT consists of a lifelong regimen of chronic blood transfusions to enable survival and suppress symptoms of the disease, and iron chelation therapy to manage iron overload that results from the transfusions. Despite the availability of supportive care, many people with TDT experience serious complications and organ damage due to underlying disease and iron overload.

Allogeneic hematopoietic stem cell transplant (HSCT) is currently the only available option to address the underlying genetic cause of TDT, though it carries significant risks. Complications of allogeneic HSCT include a risk of treatment-related mortality, graft failure, graft-versus-host disease (GvHD) and opportunistic infections, particularly in patients who undergo non-sibling matched allogenic HSCT.

On December 10,2017 AOP Orphan Pharmaceuticals AG (AOP Orphan) reported that the latest follow-up results on Ropeginterferon alfa-2b from AOP Orphan´s trial CONTINUATION-PV for patients with Polycythemia Vera (PV) were presented at ASH (Free ASH Whitepaper) 2017(Press release, AOP Orphan Pharmaceuticals, DEC 10, 2017, View Source [SID1234522508]).

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CONTINUATION-PV is an open-label, multicenter, phase IIIb study assessing the long-term efficacy and safety of Ropeginterferon alfa-2b versus hydroxyurea (HU) or best available treatment (BAT) in patients with polycythemia vera who previously participated in the pivotal PROUD-PV study.

Ropeginterferon alfa-2b is a novel, long-acting, mono-pegylated proline interferon (ATC L03AB15). It is administered once every 2 weeks, or monthly during long-term maintenance, and is expected to be the first interferon approved for PV worldwide. AOP Orphan´s submission for marketing authorization in the EU is currently under EMA review.

At 12 months (PROUD-PV study), Ropeginterferon alfa-2b was shown to be non-inferior in Complete Hematologic Response (CHR) and to have a significantly better safety and tolerability profile compared to hydroxyurea (HU).

At 24 months, treatment with Ropeginterferon alfa-2b achieved a high CHR of 70.5%, significantly higher than a CHR of 49.3% with HU/BAT (p=0.0101).
Importantly, response rates increased steadily in the Ropeginterferon alfa-2b-treated patients over the two-year treatment period in contrast to HU/BAT. Also, the composite endpoint, CHR including disease symptom improvement, was higher in patients treated with Ropeginterferon alfa-2b versus HU/BAT at 24 months (49.5% versus 36.6%, p=0.1183).
A pronounced treatment effect of Ropeginterferon alfa-2b was also observed on the mutant JAK2 allele burden at 24 months: 69.6% of patients treated with Ropeginterferon alfa-2b compared to only 28.6% on HU/BAT achieved partial molecular response (p=0.0046).

A comparable number of patients experienced treatment-related adverse events (70.1% for Ropeginterferon alfa-2b and 77.2% for HU). Events of special interest for the interferon alfa-class, in particular thyroid disorders and depression were below 5% in the Ropeginterferon alfa-2b arm. Notably, disease- or treatment-related secondary malignancies including two leukemias occurred only in the HU cohort.

Professor Heinz Gisslinger from the Medical University of Vienna, presenting the results at ASH (Free ASH Whitepaper) stated, "the observed superior efficacy of Ropeginterferon alfa-2b over hydroxyurea/best-available-therapy after 24 months, is a clear proof of the long-term value of this treatment modality. Thus, Ropeginterferon alfa-2b will provide a valuable and safe new first line therapy for PV patients".Professor Jean-Jacques Kiladjian from the Saint-Louis Hospital & Paris Diderot University in France, concluded, "the disease modification capability of Ropeginterferon alfa-2b suggested by a significant reduction of mutant JAK2 allelic burden and the malignant clone, holds promise for improvement of progression-free survival and long-term patient benefit."

About Ropeginterferon alfa-2b
Ropeginterferon alfa-2b is a novel, long-acting, mono-pegylated proline interferon with improved pharmacokinetic properties offering improved tolerability and convenience. Ropeginterferon alfa-2b was discovered by PharmaEssentia. Ropeginterferon alfa-2b has Orphan Drug designation in the European Union and the United States of America. PharmaEssentia has exclusively licensed the rights for Ropeginterferon alfa-2b to AOP Orphan for European, Commonwealth of Independent States (CIS), and Middle Eastern markets for the development and commercialization in the field of Myeloproliferative Neoplasms (MPNs).

About Polycythemia Vera
Polycythemia Vera (PV) is a cancer of the blood-building cells in the bone marrow resulting in a chronic increase of red blood cells, white blood cells and platelets. This condition may result in circulatory disorders such as thrombosis and embolism, as well as malignant transformation to myelofibrosis or leukemia.

On December 9, 2017 Kadmon Holdings, Inc. (NYSE: KDMN) reported additional positive findings from an ongoing Phase 2 clinical trial demonstrating that KD025, its Rho-associated coiled-coil kinase 2 (ROCK2) inhibitor, was well tolerated and resulted in clinically meaningful responses in patients with chronic graft-versus-host disease (cGVHD) (Press release, , DEC 10, 2017, View Source [SID1234522516]). The results are being presented today in a poster at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta (Poster #3256).

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New data from Cohort 2 of the trial (KD025 200 mg BID; n=16) showed an Overall Response Rate (ORR) of 63%, as of a data cutoff date of November 20, 2017. Updated data from Cohort 1 (KD025 200 mg QD; n=17) showed an ORR of 65%. While data from Cohort 2 continue to mature, responses were durable in Cohort 1, lasting five months or longer in 70% of patients. Responses were also rapid: 71% of patients across Cohorts 1 and 2 achieved response by the first assessment (after 8 weeks of treatment). Responses were observed across all affected organs, including Complete Responses (CRs) in upper and lower gastrointestinal (GI) tract, mouth, skin, joints, esophagus, eyes and liver. In addition, 64% of patients from Cohorts 1 and 2 were able to reduce steroid dose, and four patients completely discontinued steroids. Eighty-three percent (83%) of patients were able to reduce dose of tacrolimus, another immunosuppressive agent used to treat cGVHD. KD025 was well tolerated, with no drug-related serious adverse events (SAEs) in either cohort.

"Treatment with KD025 has demonstrated clinical activity across multiple organs affected by cGVHD, including CRs in difficult-to-treat fibrotic manifestations such as those in eyes and joints," said Madan Jagasia, MD, MS, MMHC, Professor of Medicine; Chief, Section of Hematology-SCT, Medical Director, Division of Hematology-Oncology, Vanderbilt University Medical Center; Co-Leader, Translational Research and Interventional Oncology; Vanderbilt-Ingram Cancer Center; and study investigator. "In addition, KD025 has been well tolerated, with no drug-related SAEs, and does not appear to increase risk of infection, a common consequence of immunosuppressants frequently used to treat cGVHD."

"The overall response and durability of response observed are particularly compelling in this complex patient population, the majority of which had cGVHD involvement in four or more organs," said Harlan W. Waksal, M.D., President and CEO at Kadmon. "We will continue to observe response rate, durability and safety in this ongoing clinical trial as well as in future planned studies of KD025 in cGVHD."

The ASH (Free ASH Whitepaper) poster is now available on the Investors section of Kadmon.com, under "Presentations & Events." Additional data and analysis from the KD025-208 study will be provided on Monday, December 11, 2017, after market close (4:00 p.m. ET), via slides that will be available on the Investors section of Kadmon.com.

About KD025-208
KD025-208 is an ongoing Phase 2 clinical trial of KD025 for the treatment of cGVHD. The trial is being conducted in adults with steroid-dependent or steroid-refractory cGVHD and active disease. The dose-finding trial includes 48 patients divided into three cohorts at different dose levels (KD025 200 mg QD, 200 mg BID and 400 mg QD), enrolled sequentially following a safety assessment of each cohort. An expansion cohort of approximately 40 patients will be enrolled after the optimal dose has been determined. In October 2017, KD025 received orphan drug designation from the U.S. Food and Drug Administration for cGVHD.

About cGVHD
cGVHD is a common and often fatal complication following hematopoietic stem cell transplantation, a procedure that is often used to treat patients with cancers such as myeloma or leukemia. With cGVHD, transplanted immune cells (graft) attack the patient’s cells (host), leading to inflammation and fibrosis in multiple tissues, including skin, mouth, eye, joints, liver, lung, esophagus and GI tract.