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 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) 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 atezolizumab and Avastin showed statistically significant improvement in PFS compared with sunitinib in patients whose disease expressed PD-L1 (programmed death-ligand 1: Expression ≧1%) for the first-line treatment of locally advanced or metastatic renal cell carcinoma (RCC)(Press release, Chugai, DEC 11, 2017, View Source [SID1234522503]).

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Observations of as pre-specified subgroup analysis of the atezolizumab and Avastin combination indicated that, in people whose disease expressed PD-L1, a numerical difference favoring atezolizumab and Avastin group was seen across all patient risk factor groups (favorable, 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. As data is not fully matured, analysis for another co-primary endpoint of overall survival (OS) as well as the assessment of secondary endpoints is ongoing. Safety for the atezolizumab 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. The data of the IMmotion151 study will be presented at an upcoming oncology conference in 2018.

"Avastin is currently approved overseas for the treatment of RCC in combination with interferon. We are pleased that IMmotion151 study in which Japanese patients are participating showed the combination of atezolizumab and Avastin demonstrated an improvement in PFS," said Dr. Yasushi Ito, Senior Vice President and Head of Project & Lifecycle Management Unit. "We are committed to prepare the filing for approval in order to deliver both drugs to patients as a new treatment option as soon as possible."

About the IMmotion151 Study
A global phase III, multi-center, open label, randomized study designed to evaluate the efficacy and safety of atezolizumab plus Avastin compared to sunitinib in previously untreated patients with locally advanced or metastatic RCC.

The study’s co-primary endpoints include PFS in people whose tumors expressed PD-L1 (PD-L1 expression ≧1%) on immune cells (IC) and OS in intent to treat (ITT) population. PD-L1 expression was assessed using an immunohistochemistry (IHC) test, SP142 developed by Roche.

Depending on the presence of one or several of five risk factors, patients are classified in one of the three risk groups: "Favorable" with 0 risk factors, "Intermediate" with 1-2 risk factors and "Poor" with 3 or more factors.
Study design
915 patients were randomized into atezolizumab plus Avastin or sunitinib arm in a 1:1 ratio to receive treatment according to each group’s treatment regimen.
In Japan, Avastin is not approved for the treatment of RCC.

About atezolizumab
Atezolizumab is a monoclonal antibody designed to target a protein called PD-L1 (programmed death ligand-1), which is expressed on tumor cells and tumor-infiltrating immune cells. PD-L1 binds to PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this coupling, atezolizumab may enable to release the suppression of T cells and promotes T cells to effectively attack tumor cells.
Atezolizumab (overseas brand name: TECENTRIQ) is an anti-PD-L1 immune checkpoint inhibitor. In US, atezolizumab was granted accelerated approval for the second line treatment of locally advanced or metastatic urothelial carcinoma (mUC) by the FDA in May, 2016. The FDA also approved atezolizumab as the treatment of metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy in October, 2016 and granted accelerated approval as the first line treatment of locally advanced or mUC who are ineligible for cisplatin chemotherapy in April, 2017. In EU, EMA approved atezolizumab for the second line treatment of locally advanced or mUC, the treatment of metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy and the first line treatment of locally advanced or mUC who are ineligible for cisplatin chemotherapy in September, 2017. In Japan, the new drug application of atezolizumab for the treatment of unresectable advanced or recurrent NSCLC was filed in February, 2017.

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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.

On December 11, 2017 Juno Therapeutics, Inc. (NASDAQ: JUNO), a biopharmaceutical company developing innovative cellular immunotherapies for the treatment of cancer, and Celgene Corporation (NASDAQ: CELG) reported additional data from the TRANSCEND study of JCAR017 (lisocabtagene maraleucel; liso-cel) in patients with relapsed or refractory (r/r) aggressive B-cell non-Hodgkin lymphoma (NHL) in a presentation at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Celgene, DEC 11, 2017, View Source [SID1234522552]).

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"We are highly encouraged by the latest efficacy and tolerability data, particularly at dose level two, as these are patients with a poor prognosis who need better treatment options," said Sunil Agarwal, M.D., Juno’s President of Research and Development. "These data support a potential best-in-class profile and further support the importance of a defined cell product. We continue to enroll our pivotal cohort in DLBCL patients and over the next twelve to eighteen months we intend to explore earlier lines of therapy, additional therapeutic areas, and combinations."

TRANSCEND is an open-label, multicenter Phase 1 study to determine the safety, pharmacokinetics, and antitumor activity of JCAR017 in adult patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, follicular lymphoma Grade 3B, and mantle cell lymphoma.

The data were based on a cutoff date of October 9, 2017 and presented by Jeremy Abramson, M.D., of Massachusetts General Hospital, who is a Principal Investigator for the TRANSCEND study. They add to those disclosed on November 1, 2017 in ASH (Free ASH Whitepaper) Abstract #581.

As with previous readouts, the TRANSCEND data were presented for both the core and full groups. The core group (N=67) includes 29 patients who received dose level two (DL2 = 100 million cells), 34 patients who received dose level one (DL1 = 50 million cells), and 4 patients who received dose level one twice, approximately 14 days apart.

The core group includes patients with DLBCL (NOS and transformed from follicular lymphoma) who are ECOG Performance Status 0-1. These patients represent a high-risk patient population, with approximately 90% of treated patients having one or more predictors of poor survival, including double or triple hit lymphoma, being chemorefractory to front-line or subsequent therapies, never reaching a complete remission with prior treatments, or never having undergone an autologous transplant. Enrollment of the pivotal cohort is ongoing with the core group at DL2.

The full analysis group represents evaluable r/r patients in the DLBCL cohort (N=91), which includes an additional 24 patients with poor performance status (ECOG Performance Status 2) or with niche subtypes of aggressive NHL. In both analysis groups all efficacy data are based on at least one month of follow-up with a 28-day restaging scan and all safety evaluable data are based on having received JCAR017 (liso-cel) with at least one month of follow-up. Product was available for 98% (126/128) of patients apheresed in the DLBCL cohort.

"The results of this study continue to show the exciting potential of this CAR T therapy," said Jay Backstrom, Chief Medical Officer and Global Head of Regulatory Affairs for Celgene. "Our collaboration with Juno reflects our commitment to delivering transformational treatments to patients with blood cancers such as non-Hodgkin lymphoma."

Topline data from the presentation as of the October 9, 2017 data cutoff date included:

Responses in core group

At DL2, the data showed a 3 month overall response rate (ORR) of 74% (14/19) and a 3 month complete response (CR) rate of 68% (13/19). Of patients that have reached 6 months of follow-up, 50% (7/14) were in CR. Across doses, 80% (16/20) of patients with CR at 3 months stayed in CR at 6 months, and 92% (11/12) of patients in response at 6 months remain in response as of data cutoff.
Across doses, median duration of response (DOR) was 9.2 months and median durability of CR was not reached.
Tolerability in core group

1% (1/67) experienced severe cytokine release syndrome and 15% (10/67) experienced severe neurotoxicity.
36% (24/67) had any grade CRS and 21% (14/67) had any grade NT.
58% (39/67) had no CRS or NT of any grade.
At dose level 1, 3% (1/34) experienced severe CRS and 21% (7/34) experienced severe NT.
At dose level 2, 0% (0/29) experienced severe CRS and 7% (2/29) experienced severe NT.
13% (9/67) received tocilizumab and 18% (12/67) received corticosteroids.
Tolerability across doses in full group

1% (1/91) experienced severe CRS and 12% (11/91) experienced severe NT.
35% (32/91) had any grade CRS and 19% (17/91) had any grade NT.
60% (55/91) had no CRS or NT of any grade.
The most common treatment-emergent adverse events (TEAEs) other than CRS and NT that occurred at ≥25% included neutropenia (49%), anemia (38%), fatigue (37%), thrombocytopenia (29%), nausea (27%), and diarrhea (25%). The most common TEAEs were similar between core and full groups.
JCAR017 (liso-cel) is a defined composition CD19-directed CAR T cell product candidate using a 4-1BB costimulatory domain. Juno believes JCAR017’s clinical profile could enable outpatient administration. A biologics license application filing is expected to be completed in the second half of 2018, with approval as early as the end of 2018.

ASH Investor and Analyst Event and Webcast

The Juno ASH (Free ASH Whitepaper) Investor and Analyst Event and webcast will be held Monday, December 11, 2017 at 8:30 p.m. Eastern Time. The webcast can be accessed live on the Investor Relations page of Juno’s website, www.JunoTherapeutics.com, and will be available for replay for 30 days following the event.

On December 11, 2017 Fate Therapeutics, Inc. (NASDAQ:FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported Day 100 clinical data from the Phase 1 stage of its PROTECT clinical trial of ProTmune, the Company’s next-generation hematopoietic cell graft for patients with hematologic malignancies (Press release, Fate Therapeutics, DEC 11, 2017, View Source [SID1234522554]). All seven subjects receiving ProTmune remained alive and relapse-free during the first 100 days following hematopoietic cell transplantation (HCT). Three of the seven subjects experienced acute graft-versus-host disease (GvHD) during the first 100 days following HCT. Each of these three subjects responded to standard-of-care steroid treatment with a median time to resolution of the maximum GvHD grade of 7 days [range: 5-8 days].

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"The significant risk of GvHD limits broad application of allogeneic transplant due to uncertainty of its short- and long-term impact on the recipient. It occurs frequently with variable intensity and can be a devastating disease when unresponsive to treatment. The requisite extended use of immunosuppressive agents to treat GvHD compromises the anti-leukemia activity of the transplant procedure and can significantly increase the risk of cancer relapse and mortality while also placing patients at risk for opportunistic infection," said Richard Maziarz, M.D., Principal Investigator, Oregon Health Sciences University. "The administration of a hematopoietic cell graft that is optimized to attenuate T-cell alloreactivity and maintain the graft’s anti-leukemia activity is a novel and highly-attractive therapeutic approach to decrease the risk and enhance the curative potential of allogeneic transplantation."

PROTECT Phase 1 Day 100 Clinical Results

Clinical data from the Phase 1 stage of PROTECT were presented today by Dr. Maziarz during a poster session at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. The Phase 1 stage included seven adult subjects with hematologic malignancies undergoing matched unrelated donor HCT following myeloablative conditioning. During the first 100 days following HCT, all seven subjects receiving ProTmune remained alive and relapse-free. Three of the seven subjects experienced acute GvHD during the first 100 days following HCT, all of whom responded to standard-of-care steroid treatment. The median time to resolution of the maximum GvHD grade was 7 days [range: 5-8 days]. There were no events of graft failure, and there were no ProTmune-related serious adverse events reported by investigators.

PROTECT Day 100 Clinical Data
Subject 1 2 3 4 5 6 7
Hematologic Malignancy MDS AML AML ALL ALL ALL AML
CD34+ cell dose (x106/kg) 10.3 4.6 10.9 4.8 3.2 3.0 9.4
CD3+ cell dose (x108/kg) 3.1 1.8 2.6 2.8 2.0 1.2 2.8
ProTmune-related SAEs None None None None None None None
Day of Neutrophil Engraftment 1 Day 14 Day 18 Day 22 Day 15 Day 16 Day 18 Day 19
Acute GvHD / Grade (CIBMTR) None None Grade 2 None Grade 2 Grade 3 None
Treatment Responsive — — Yes — Yes Yes —
Time to Resolution of Maximum Grade — — 7 days — 8 days 5 days —
Cancer Relapse-free Yes Yes Yes Yes Yes Yes Yes
Survival Yes Yes Yes Yes Yes Yes Yes
1 As measured from the day following HCT

"The Day 100 clinical results from our Phase 1 stage of PROTECT support the unique therapeutic potential of ProTmune to reduce graft-versus-host disease and promote relapse-free survival. We are very encouraged by these initial clinical findings and the potential of ProTmune to deliver transformative benefits to cancer patients," said Chris Storgard, M.D., Chief Medical Officer of Fate Therapeutics. "The randomized, controlled and double-blinded Phase 2 stage of PROTECT is enrolling subjects at 14 U.S. centers of excellence. Given the high rates of morbidity and mortality underlying hematopoietic cell transplantation, we have also engaged the FDA, under our Fast Track designation for ProTmune, to discuss the necessary activities for product registration."

All subjects receiving ProTmune in the PROTECT Phase 1 stage are being followed for a period of two years following HCT. As of a November 29, 2017 data cut-off, all subjects remained relapse-free, and there were no events of graft failure and no serious adverse events related to ProTmune reported by investigators. Non-relapse mortality was reported in two subjects (Subject 1 on Day 228; Subject 3 on Day 151). Five of seven subjects remained on study with median time on study of 154 days [Day 106 — 254].

PROTECT Phase 2 Design
The Phase 2 stage of PROTECT is a randomized, controlled and double-blinded clinical trial assessing the safety and efficacy of ProTmune in up to 60 adult subjects with hematologic malignancies undergoing matched unrelated donor HCT following myeloablative conditioning. Subjects are being randomized, in a 1:1 ratio, to receive either ProTmune or a conventional matched unrelated donor mobilized peripheral blood cell graft. The primary efficacy endpoint of PROTECT is cumulative incidence of Grades 2-4 acute GvHD by Day 100 following HCT, where prospective clinical studies have shown that 40% to 80% of patients undergoing matched unrelated donor transplant experience Grades 2-4 acute GvHD. Immunosuppressant treatments are effective in only about half of affected HCT patients and are associated with a marked increase in severe infections and cancer relapse. Additional endpoints, such as rates of cancer relapse, chronic GvHD, non-relapse mortality and overall survival, are also being assessed. Fourteen U.S. centers are currently open for enrollment in the Phase 2 stage of PROTECT.

About Acute GvHD
Acute graft-versus-host disease (GvHD) is a severe immunological disease that commonly arises in patients during the first weeks following allogeneic HCT when newly-transplanted donor immune cells attack the patient’s tissues and organs, resulting in a potentially fatal immune system reaction. Prospective clinical studies have shown that 40% to 80% of patients undergoing matched unrelated donor transplant experience Grades 2-4 acute GvHD, with most incidents occurring by Day 60 following HCT despite the use of standard prophylaxis regimens. The disease is the leading cause of early morbidity and mortality in matched unrelated donor transplant, where death directly attributable to acute GvHD or its treatment occurs in 10% to 20% of patients. There are currently no FDA-approved preventive therapies and very few treatment options for acute GvHD.

About ProTmune
ProTmune is an investigational next-generation hematopoietic cell graft for the prevention of acute graft-versus-host disease (GvHD) in patients undergoing allogeneic hematopoietic cell transplantation. ProTmune is manufactured by pharmacologically modulating a donor-sourced, mobilized peripheral blood graft ex vivo with two small molecules (FT1050 and FT4145) to decrease the morbidity and mortality of acute GvHD while maintaining the anti-leukemia activity of the graft. ProTmune has been granted Orphan Drug and Fast Track Designations by the U.S. Food and Drug Administration, and Orphan Medicinal Product Designation by the European Commission.