On December 11, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the Phase III IMmotion151 study met its co-primary endpoint of investigator-assessed progression-free survival (PFS) and demonstrated that the combination of Tecentriq (atezolizumab) and Avastin (bevacizumab) provided a statistically significant and clinically meaningful reduction in the risk of disease worsening or death (PFS) in people whose disease expressed the PD-L1 (programmed death-ligand 1: Expression ≥1%) protein compared with sunitinib for the first-line treatment of people who have advanced or metastatic renal cell carcinoma (mRCC) (Press release, Hoffmann-La Roche, DEC 11, 2017, View Source [SID1234522504]).

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Observations of a pre-specified subgroup analysis of the Tecentriq and Avastin combination indicated that, in people whose disease expressed PD-L1, a numerical difference favouring Tecentriq was seen across all patient risk factor groups (favourable, intermed­iate and poor) compared to sunitinib; however, due to the study design these data could not be assessed for statistical significance and are descriptive only. Assessment of secondary endpoints is ongoing. Safety for the Tecentriq and Avastin combination appeared consistent with the known safety profile of the individual medicines and what was previously reported in the Phase II IMmotion150 study. No new safety signals were identified with the combination.

Results will be presented at an upcoming oncology conference in 2018. Top-line results from the co-primary endpoint of overall survival (OS) are not mature.

"We are encouraged by these results as they add to the emerging body of evidence that supports our rationale for this combination. We believe that the regimen of Tecentriq and Avastin may enhance the potential of the immune system in the initial treatment of advanced kidney cancer," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We will discuss these data with health authorities globally and hope to bring this combination forward as a potential new treatment option to patients as soon as possible.’’
IMmotion151 is the second successive positive Phase III study of Tecentriq that includes an Avastin combination component as an initial treatment. This follows the positive Phase III non-squamous non-small cell lung cancer (NSCLC) IMpower150 study that showed Tecentriq and Avastin plus chemotherapy demonstrated a PFS advantage over Avastin plus chemotherapy.

About the IMmotion151 study
IMmotion151 is a Phase III multicentre, randomised, open-label study to evaluate the efficacy and safety of Tecentriq and Avastin versus sunitinib in people with inoperable, locally advanced or metastatic renal cell carcinoma (RCC) who have not received prior systemic active or experimental therapy. It enrolled 915 people globally who were randomised 1:1 to receive Tecentriq and Avastin, or sunitinib alone.

People in the Tecentriq and Avastin arm received Tecentriq at a fixed dose of 1200 milligrams (mg) and Avastin at a dose of 15 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 3 weeks until loss of clinical benefit or unacceptable toxicity. People in the sunitinib arm received sunitinib 50 mg orally, once daily for 4 weeks followed by 2 weeks rest until loss of clinical benefit or unacceptable toxicity.

The co-primary endpoints were PFS, as determined by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) in people whose tumours expressed PD-L1 [PD-L1 expression ≥1 percent on immune cells (IC)], and OS in the overall study population (intention-to-treat, ITT). PD-L1 expression was prospectively assessed using an immunohistochemistry (IHC) test (SP142) developed by Roche Tissue Diagnostics.
Stratification factors included the presence or absence of liver metastases; level of IC staining for PD-L1 (≥1 percent vs. <1 percent) and Memorial Sloan-Kettering Cancer Center (Motzer) risk score. The Motzer prognostic scoring system predicts for OS based upon an individual’s baseline clinical and laboratory characteristics.
Depending on the presence of one or several of five variables (risk factors), patients are classified in one of the three risk groups: ‘Favourable’ with 0 risk factors, ‘Intermediate’ with 1–2 risk factors and ‘Poor’ with ≥ 3 risk factors.

About RCC
Kidney cancer remains one of the most common cancers in the world, accounting for over 140,000 deaths worldwide each year,1 with renal cell carcinoma (RCC) accounting for approximately 90% of all cases.2 Over 300,000 people are diagnosed with RCC every year and currently only about 1 in 10 people are alive beyond 5 years following diagnosis of metastatic disease.

RCC occurs when abnormal cells develop in the tissue of the kidneys, specifically in the small tubes (also known as tubules) where our blood is filtered.4 Typically, RCC is a single tumour in one kidney but, in rare cases, there can be multiple tumours, which can occur in one or both kidneys.

Despite recent progress in the field of kidney cancer, treatment options for people with the disease remains limited.

About Tecentriq (atezolizumab)
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Tecentriq is already approved in the European Union, United States and more than 50 countries for people with previously treated metastatic NSCLC and for people with locally advanced or metastatic urothelial cancer (mUC) who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy.

About Avastin (bevacizumab) in RCC
Avastin (bevacizumab) is an anti-VEGF inhibitor. VEGF (vascular endothelial growth factor) is a protein that stimulates the formation and maintenance of blood vessels and has been shown to play a key role in the development of RCC.
RCC tumours are highly vascularised, meaning they have many blood vessels and also exhibit a high concentration of VEGF5. There is, therefore a strong rationale for medicines such as Avastin that block the VEGF pathway. Avastin is the only currently available treatment for patients with mRCC that directly inhibits VEGF.

There is a strong scientific rationale to support further investigation of Tecentriq and Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat first-line advanced NSCLC and mRCC. Avastin, in addition to its established anti-angiogenic effects, may further enhance Tecentriq’s ability to restore anti-cancer immunity, by inhibiting VEGF-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.
To learn more about the Roche approach to cancer immunotherapy please follow this link:
View Source

On December 11, 2017 ADC Therapeutics (ADCT), an oncology drug discovery and development company that specializes in the development of proprietary Antibody Drug Conjugates (ADCs) targeting major cancers, reported clinical data from two ongoing Phase I clinical trials evaluating ADCT-301 (camidanlumab tesirine or "Cami-T") in important subtypes of lymphoma and leukemia (Press release, ADC Therapeutics, DEC 11, 2017, View Source [SID1234522513]). The data were presented at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, USA.

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1. Interim results of a Phase I open label, single agent, dose-escalating study of ADCT-301 evaluating tolerability, safety, pharmacokinetics and efficacy in patients with relapsed or refractory B-cell Hodgkin’s or non-Hodgkin’s lymphoma

Dr. Steven M. Horwitz, Medical Oncologist at Memorial Sloan Kettering Cancer Center in New York City, and Principal Investigator, said: "Despite considerable advances in the treatment of lymphoma, a significant number of patients still relapse or become refractory to existing therapies and need new treatment options. We are excited by the 77 percent overall response rate (ORR) in Hodgkin Lymphoma (HL), including a 44 percent complete response rate. We are also seeing emerging efficacy signals in T-cell lymphomas (ORR: 33 percent) and B-cell lymphomas (ORR: 19 percent). Although still early, we are very encouraged by a median duration of response for HL patients of over 5 months to-date. The safety profile appears consistent with what we expect with this target and warhead. We are now working to determine the best dosing regimen for Phase II."

Data were presented from 86 evaluable, heavily pre-treated patients who had failed, or were intolerant to, any established therapy known to provide clinical benefit. The median age of patients was 53 years and they had a median of 4 prior therapies. Data were reported from Part 1 and Part 2 of the Phase I study as of November 1, 2017. In Part 1 (dose escalation), 71 patients were treated at dose ranges from 3-150 µg/kg every three weeks. In Part 2 (dose expansion), 15 Hodgkin Lymphoma patients were treated at 45 µg/kg every 3 weeks.

Key findings presented at the poster presentation included:

For the 27 response-evaluable patients with HL in Part 1, treated at doses greater than or equal to 45 µg/kg, the ORR was 77 percent (21/27 patients) with 12 patients achieving a complete response (44 percent) and 9 patients achieving a partial response (33 percent).
For the 12 response-evaluable patients with HL in Part 1 and Part 2, treated at the 45 µg/kg dose, the ORR was 100 percent (12/12) with 6 patients achieving a complete response (50 percent) and 6 patients achieving a partial response (50 percent).
For HL patients in Part 1 and Part 2, treated at doses greater than or equal to 45 µg/kg, a complete or partial response was achieved in 21 of 27 patients previously treated with brentuximab vedotin (77 percent), 13 of 18 patients previously treated with a checkpoint inhibitor (72 percent), 9 of 14 patients who had previously undergone a stem cell transplantation (64 percent), and 4 of 8 patients who had previously received all three of these treatments (50 percent).
ADCT-301 has been reasonably well tolerated.
The most common treatment-emergent adverse events of any grade occurring in at least 20 percent of patients in Part 1 and Part 2 were fatigue (30 percent), rash (26 percent), elevated gamma-glutamyltransferase (22 percent), and pyrexia (21 percent). The most common Grade 3 or 4 adverse events occurring in at least 5 percent of patients, regardless of attribution, were elevated gamma-glutamyltransferase (13 percent), reduced platelet count (9 percent), elevated alanine aminotransferase (6 percent), anemia (6 percent), and rash (6 percent). There were three heavily pre-treated patients diagnosed with auto-immune neurotoxicity, including two patients who developed Guillain-Barré syndrome.
These encouraging preliminary safety and efficacy results support further characterization of the dosing regime to optimize the therapeutic window in Hodgkin Lymphoma for a Phase II study.
2. Interim results of a Phase I open label, single agent, dose-escalating study of ADCT-301 evaluating tolerability, safety, pharmacokinetics and efficacy in patients with relapsed or refractory B-cell acute myeloid leukemia or acute lymphoblastic leukemia

Data were presented from 33 evaluable, heavily pre-treated, patients who had failed, or were intolerant to, any established therapy known to provide clinical benefit. The median age of patients was 67 years and they had a median of 3 prior therapies. In Part 1 (dose escalation), 33 patients were treated at dose ranges from 3-92 µg/kg every three weeks, or 30-37.5 µg/kg once weekly.

Key findings presented at the poster presentation included:

One patient achieved a complete response with incomplete blood count recovery.
ADCT-301 has shown an acceptable safety profile.
The most common treatment-emergent adverse events of any grade occurring in at least 20 percent of patients were fatigue (30 percent), nausea (24 percent), febrile neutropenia (21 percent), and pneumonia (21 percent). The most common Grade 3 or 4 adverse events occurring in at least 10 percent of patients, regardless of attribution, were febrile neutropenia (21 percent), thrombocytopenia (15 percent), fatigue (12 percent), reduced neutrophil count (12 percent), and pneumonia (12 percent).
Dose escalation will continue to investigate weekly dosing.
About ADCT-301

ADCT-301 is an antibody-drug conjugate (ADC) composed of a monoclonal antibody that binds to CD25 (HuMax-TAC, licensed from Genmab A/S), conjugated to a pyrrolobenzodiazepine (PBD) dimer toxin. Once bound to a CD25-expresing cell, ADCT-301 is internalized into the cell where enzymes release the PBD-based warhead. CD25 is an attractive target for an ADC approach as it is expressed in a wide range of hematological malignancies, including certain forms of lymphomas and leukemias, while its expression in healthy organs is restricted. ADCT-301 is being evaluated in two ongoing phase Ia/Ib clinical trials in patients with relapsed or refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), and in patients with relapsed or refractory CD25-positive acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). (www.adct-301.com)

On December 11, 2017 TG Therapeutics, Inc. (NASDAQ:TGTX), reported the presentation of six posters highlighting preclinical and clinical data sets for TGR-1202 (umbralisib), the Company’s once-daily PI3K delta inhibitor, and TG-1101 (ublituximab), the Company’s novel glycoengineered anti-CD20 monoclonal antibody, at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting, currently being held at the Georgia World Congress Center in Atlanta, Georgia (Press release, TG Therapeutics, DEC 11, 2017, View Source [SID1234522535]).

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, stated, "We are very pleased by the data presented yesterday and today during the ASH (Free ASH Whitepaper) annual meeting. The preclinical data help us to better understand the difference between TGR-1202 and other agents in the class and offers a more complete rationale for the differentiated safety profile seen in the clinic. With the updated and expanded integrated safety analysis of TGR-1202 alone and in combination with other agents, we believe we have provided the long-term follow-up sufficient to allay any lingering safety concerns related to TGR-1202 caused by the toxicity profile of first generation PI3K delta inhibitors." Mr. Weiss continued, "In 2018, with registration-directed data expected in CLL and NHL, our focus will turn to showcasing the efficacy of TGR-1202 and our proprietary combination of TG-1101 plus TGR-1202, our U2 combination, ideally leading to NDA/BLA filings in CLL and NHL."

The following summarizes the highlights from each poster presented at the ASH (Free ASH Whitepaper) 2017 meeting.

Clinical Data Presentations:

An Integrated Safety Analysis of the Next Generation PI3K Delta Inhibitor Umbralisib (TGR-1202) in Patients with Relapsed/Refractory Lymphoid Malignancies

This presentation includes data that were pooled from 5 completed or ongoing Phase 1 or 2 studies containing TGR-1202, including a total of 347 patients with relapsed or refractory hematologic malignancies. Patients were heavily pretreated, with 50% of patients having seen 3 or more prior lines of therapy.

Highlights from this poster include:

347 patients have been treated with TGR-1202 across the 5 studies in this pooled analysis, with median duration of exposure of 6.5 months, and 176 patients on drug for 6+ months, 104 patients for 12+ months, with the longest patients on daily TGR-1202 for 4+ years
In longer follow-up and in an expanded patient population, TGR-1202 exhibits a differentiated safety profile compared to prior generation PI3K delta inhibitors
Discontinuations due to adverse events (AEs) were rare at under 10% for all studies
Grade 3/4 AEs commonly associated with PI3K delta inhibitors have been rare, with pneumonitis ( < 0.5%), transaminitis (~2%) and colitis ( < 1%), the latter occurring with no apparent association to time on therapy
Improved tolerability with few discontinuations due to AEs has allowed patients to remain on continuous dosing to achieve and sustain promisingly high rates of response:
• 85% Overall Response Rate (ORR) for single agent TGR-1202 in relapsed/refractory Chronic Lymphocytic Leukemia (CLL)
• 53% ORR for single agent TGR-1202 in relapsed/refractory Follicular Lymphoma (FL)
KI Intolerance Study: A Phase 2 Study to Assess the Safety and Efficacy of Umbralisib (TGR-1202) In Patients with Chronic Lymphocytic Leukemia (CLL) Who Are Intolerant to Prior BTK or PI3K-delta Inhibitor Therapy (Abstract Number 4314)

This poster presentation includes data from patients with CLL who are intolerant to prior BTK or PI3K delta inhibitor therapy who were then treated with single agent TGR-1202. To be eligible for the study patients had to have received prior treatment with a BTK inhibitor (ibrutinib, acalabrutinib) or a PI3K delta inhibitor (idelalisib, duvelisib) and discontinued therapy due to intolerance within 12 months of starting treatment on this study. Thirty-three patients were evaluable for safety (30 patients with ibrutinib intolerance, and 3 patients with idelalisib intolerance) of which 32 were evaluable for efficacy (1 patient had a confirmed Richter’s Transformation (RT) at enrollment which did not meet eligibility criteria). TGR-1202 appears to demonstrate a favorable safety profile in patients intolerant to prior ibrutinib or idelalisib, with only 2 patients (6%) discontinuing due to an adverse event, neither of which was a recurrent AE from prior TKI therapy.

Highlights from this poster include:

94% (30 of 32) of patients remain progression-free
Median time on study at the data cut off was approximately 6 months with the majority of patients continuing on study and follow-up ongoing
No patient discontinued TGR-1202 due to a recurrent AE which led to discontinuation from their prior kinase inhibitor
Phase I/II Study of Pembrolizumab in Combination with Ublituximab (TG-1101) and Umbralisib (TGR-1202) in Patients with Relapsed/Refractory CLL (Abstract Number 3010)

This presentation includes data from patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) or Richter’s Transformation (RT) treated with the triple combination of TG-1101, TGR-1202, and pembrolizumab. Eleven patients were evaluable for safety (9 CLL patients and 2 RT patients) and 10 were evaluable for efficacy (9 CLL and 1 RT), with one patient too early to evaluate.

Highlights from this poster include:

One AE of increased LFTs was observed which met criteria for DLT; patient was re-challenged and remains on study treatment with TGR-1202 maintenance now 15+ months
78% (7 of 9) ORR in patients with relapsed/refractory CLL
75% (3 of 4) ORR in BTK refractory CLL patients
Responses have been durable with the first patient progression-free for 24+ months
Preclinical Data Presentations:

Differential Regulation of T Cells By PI3K Delta Inhibitors in a CLL Murine Model (Abstract Number: 3009)

This poster presentation included preclinical data describing the differential regulation of human T cells by TGR-1202 in a preclinical CLL murine model.

Highlights from this poster include:

TGR-1202 oral treatment induced less incidence of toxicity in CLL mice compared to other PI3K delta inhibitors
TGR-1202 relatively preserved Treg quantity and function in a dose dependent manner compared to other PI3K delta inhibitors in normal and murine CLL T cells
Inhibition of casein-kinase 1 epsilon (CK1e) by TGR-1202 may explain the relative preservation of Treg cells in these in-vivo models
Umbralisib/TGR-1202 As a Novel Dual PI3K/CK1 Inhibitor Has a Unique Therapeutic Role in Silencing Oncogenes in Aggressive Lymphomas (Abstract Number 2809)

This poster presentation expanded on existing preclinical data demonstrating that TGR-1202 is synergistic with carfilzomib in certain aggressive lymphoma cell lines.

Highlights from this poster include:

TGR-1202 is highly synergistic with the proteasome inhibitor carfilzomib in cell line models of double hit lymphoma and mantle cell lymphoma
Based on this preclinical work, a Phase 1 clinical study to evaluate the safety and efficacy of TGR-1202 in combination with carfilzomib is currently enrolling patients
PI3K Delta Inhibitors Induce Primary Monocyte Cytotoxicity but Do Not Alter Monocyte Differentiation (Abstract Number 4284)

This poster presentation included preclinical data exploring the effect of PI3K delta inhibitors on monocyte activity.

Highlights from this poster include:

The clinical benefit and initial lymphocytosis seen with PI3K delta inhibitors in CLL may be related in part to direct effects on monocyte derived cells
Idelalisib and TGR-1202 differed in the extent of monocyte cytotoxicity induced and inhibition of pAKT
The direct effects of PI3K delta inhibitors on monocytes suggests these drugs may have efficacy beyond B-cell malignancies, including in monocytic neoplasms or other malignancies with monocyte derived cells in the tumor microenvironment
The above referenced presentations, are available on the Publications page of the Company’s website at www.tgtherapeutics.com.

On December 11, 2017 Nippon Kayaku presented Annual Report 2017 (Presentation, Nippon Kayaku, DEC 11, 2017, View Source;sid=43565&code=4272 [SID1234522559]).

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On December 11, 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 the ongoing HGB-205 clinical study of its LentiGlobin gene therapy product candidate in patients with severe sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT) (Press release, bluebird bio, DEC 11, 2017, View Source [SID1234522550]). The findings will be presented today in a poster session at the 59th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper).

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"People with SCD and TDT experience serious complications and organ damage as a result of their disease and complications from chronic blood transfusions. Addressing the underlying genetic causes of these diseases has the potential to dramatically improve patient outcomes," said Dave Davidson, M.D., chief medical officer, bluebird bio. "All three patients with severe SCD in the HGB-205 study showed a steady increase in HbAT87Q production in the first six months following LentiGlobin therapy, with the longest-treated patient showing stable hemoglobin levels over two and a half years. All four patients with TDT are transfusion-free following therapy, up to almost four years in the first patient treated. The durable treatment effects observed to date in this study are encouraging, particularly given the manufacturing process improvements that we implemented across our subsequent clinical studies of LentiGlobin, and additional changes to the HGB-206 study protocol that we hope will further improve outcomes for patients with SCD."

These data will be presented by Marina Cavazzana, M.D., Ph.D., Professor of Medicine at Paris Descartes University and Research Director at the Centre for Clinical Research in Biotherapy, Necker Hospital, and at the Institute of Genetic Diseases, Imagine, Paris, France. Professor Cavazzana is the primary investigator of the HGB-205 study.

"All seven patients in this study continue to experience notable clinical improvement. Since being treated with LentiGlobin therapy, the four patients with TDT have been free of chronic transfusions with near normal and stable levels of total hemoglobin," said Professor Cavazzana. "While progress has been made with medications to treat SCD and TDT, we are in need of better options for our patients. This study suggests that LentiGlobin has the potential to be a transformational one-time therapy for people with SCD and TDT."

Longer Term Follow-up on the First Patients with Severe Hemoglobinopathies Treated with LentiGlobin Gene Therapy (Poster Abstract #4609)

Presenter: Marina Cavazzana, M.D., Ph.D. Necker-Enfants Malades Hospital, Paris, France

Poster Session Date & Time:Monday, December 11 at 6:00 p.m.

Location: Building A, Level 1, Hall A2

HGB-205 is an ongoing, open-label, single-center Phase 1/2 study designed to evaluate the safety and efficacy of LentiGlobin drug product (DP) in the treatment of patients with severe SCD and TDT. The study enrolled three patients with severe SCD and four patients with TDT, who have undergone infusion with LentiGlobin DP. Results as of September 20, 2017 include:

SCD:

All three treated patients showed rising HbAT87Q levels in the first six months.
Patient 1204 was 13 years old at study enrollment. At last follow-up (35.2 months), this patient had a total hemoglobin of 12.4 g/dL, of which 6.1 g/dL was HbAT87Q (52 percent anti-sickling Hb). HbAT87Q concentration in this patient has remained stable since approximately nine months post-infusion. The patient continues to show marked clinical improvement.
Patient 1207 was 16 years old at study enrollment. At last follow-up (8.9 months), this patient had a total hemoglobin of 10.0 g/dl, of which 0.7 g/dl was HbAT87Q (14 percent anti-sickling Hb). This patient had a pre-treatment history of frequent episodes of vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) despite hydroxyurea prior to beginning regular transfusions. Patient 1207 had episodes of ACS and hospitalization at six and eight months post-treatment, and received three transfusions.
Patient 1208 was 21 years old at study enrollment. At last follow-up (6.0 months), this patient had a total hemoglobin of 10.6 g/dL, of which 2.7 g/dL was HbAT87Q (46 percent total anti-sickling Hb). This patient had a pre-treatment history of frequent episodes of VOCs and ACS prior to beginning regular transfusions, and was still symptomatic while receiving regular transfusions. Following LentiGlobin treatment, Patient 1208 has had no episodes of VOCs or ACS (with six months follow-up).
TDT:

All four patients with TDT have remained free of chronic transfusions since shortly after receiving LentiGlobin DP.
Patient 1201 (β0/βE genotype) has been free of transfusions for 45.2 months with total hemoglobin of 10.1 g/dL, of which 6.7 g/dL was HbAT87Q.
Patient 1202 (β0/βE genotype) has been free of transfusions for 40.1 months with total hemoglobin of 12.9 g/dL, of which 10.1 g/dL was HbAT87Q.
Patient 1206 (β0/βE genotype) has been free of transfusions for 23.8 months with total hemoglobin of 11.1 g/dL, of which 8.0 g/dL was HbAT87Q.
Patient 1203, who is homozygous for the severe β+ mutation IVS1-110, has been free of transfusions for 20.9 months with total hemoglobin of 8.7 g/dL, of which 6.7 g/dL was HbAT87Q.
Three of four patients (1201, 1202 and 1206) were able to begin therapeutic phlebotomy. Patient 1202 subsequently discontinued iron chelation and phlebotomy.
The safety profile of LentiGlobin DP continues to be consistent with myeloablative conditioning with single-agent busulfan. No DP-related adverse events have been observed, and there is no evidence of clonal dominance.
About SCD
Sickle cell disease (SCD) is an inherited disease caused by a mutation in the beta-globin gene, that produces βS-globin. High levels of HbS in patients with SCD are responsible for the characteristic chronic anemia, vaso-occlusive crises, and other acute and chronic manifestations of SCD which lead to significant morbidity and early mortality.

Where adequate medical care is available, common treatments for patients with SCD largely revolve around prevention of infection and management and prevention of acute sickling episodes. Chronic management may include hydroxyurea and, in certain cases, chronic transfusions. Allogeneic hematopoietic stem cell transplant (HSCT) is currently the only available option to address the underlying genetic cause of SCD, though it carries significant risk. 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 allogeneic HSCT.

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 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, GvHD and opportunistic infections, particularly in patients who undergo non-sibling matched allogenic HSCT.

About the HGB-205 Study
HGB-205 is an ongoing, open-label Phase 1/2 study designed to evaluate the safety and efficacy of LentiGlobin in the treatment of subjects with TDT and SCD. The study enrolled seven subjects who will be followed to evaluate safety and transfusion requirements post-transplant. Among patients with sickle cell disease only, efficacy will also be measured based on the number of vaso-occlusive crises or acute chest syndrome events. For more information on the HGB-205 study, please visit clinicaltrials.gov using identifier NCT02151526.