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Valemetostat Data at EHA Shows Promising Durable Tumor Response in Patients with Peripheral T-Cell Lymphoma and Adult T-Cell Leukemia/Lymphoma

On June 11, 2021 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that New data from for valemetostat, a potential first-in-class specific and potent dual inhibitor of EZH1 and EZH2, showed promising and durable tumor response in patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) and adult T-cell leukemia/lymphoma (ATL).1,2 The data were reported today during an oral presentation (Abstract #S218) at the Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) (#EHA2021) (Press release, Daiichi Sankyo, JUN 11, 2021, View Source [SID1234583911]).

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PTCL is a group of rare and heterogenous malignancies, including ATL, which represent about 10-15% of all non-Hodgkin lymphomas (NHL).3 The majority of patients with PTCL experience disease progression following initial treatment with a multi-drug chemotherapy-based regimen, and median overall survival following relapse is approximately 5.8 months.4 New innovative treatment strategies are needed to improve survival in these patients.

In this first-in-human phase 1 study of valemetostat in B-cell and T-cell NHL, data were reported at EHA (Free EHA Whitepaper) in the subset of patients with relapsed/refractory PTCL and ATL. The objective response rate (ORR), based on investigator’s assessment, was 54.5% (CI 95%: 38.8-69.6) in 44 patients with PTCL including 12 complete responses (CRs) and 12 partial responses (PRs). A median duration of response (DOR) of 56.00 weeks (CI 95%: 44.43-NE) and a median progression-free survival (PFS) of 52.00 weeks (CI 95%: 16.14-NE) were observed after a median follow-up of 19.93 weeks (range: 3.1-68.1).

The ORR in 14 patients with ATL was 57.1% (CI 95%: 28.9-82.3), with four CRs and four PRs. Median DOR and PFS were not estimable for patients with ATL after a median follow-up of 23.07 weeks (range: 3.3-125.0). Twelve patients with PTCL and six patients with ATL remained on treatment with valemetostat at the time of data cutoff on November 2, 2020.

The safety profile of valemetostat in patients with PTCL and ATL (n=58) was similar with that seen across all patients with NHL (n=77). Grade 3 or higher treatment emergent adverse events (TEAEs) occurred in 54 of 77 NHL patients (70.1%) and included neutrophil count decrease (23.4%), lymphocyte count decrease (22.1%), platelet count decrease (16.9%), white blood cell count decrease (15.6%), anemia (11.7%), diarrhea (1.3%) and alanine aminotransferase (ALT) increase (1.3%). Dose interruption or reductions due to TEAEs occurred in 41.6% (n=32) and 10.4% (n=8) of all patients with NHL, respectively.

"The proportion of patients who responded to valemetostat and the durability of responses observed in this trial are very encouraging for patients with PTCL, including ATL, which remains one of the most significant areas of unmet need in the treatment of hematologic cancers," said Shigeru Kusumoto, MD, Associate Professor, Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Japan. "Because both EZH1 and EZH2 play important roles for the pathophysiology of PTCL and ATL, dual targeting of EZH1 and EZH2 with valemetostat may be an innovative approach for these difficult-to-treat diseases."

"We are committed to translating the novel mechanism of valemetostat into a potential treatment option for patients with PTCL and ATL in various regions around the world where these types of blood cancers are most prevalent," said Ken Takeshita, MD, Global Head of Research and Development, Daiichi Sankyo. "Based on the promising clinical activity seen in this phase 1 study, we have initiated VALENTINE-PTCL01, a global pivotal study that will further evaluate the efficacy and safety of valemetostat in patients with relapsed or refractory PTCL including ATL."

Patients with PTCL enrolled in the study had received a median of two prior treatments (range: 1-8), including prior hematopoietic stem cell transplantation (HSCT; 20.5%). Patients with ATL had received a median of two prior treatments (range: 1-8), including HSCT (14.3%).

Summary of Phase 1 Results

Efficacy Measure

Valemetostat Phase 1 Dose Expansion 200 mg (n=58)

PTCLiii, iv (n=44)

ATLv,vi (n=14)

ORR (%) (95% CI) i,ii

54.5% (38.8-69.6)

57.1% (28.9-82.3)

12 (27.3)

4 (28.6)

12 (27.3)

4 (28.6)

5 (11.4)

2 (14.3)

8 (18.2)

3 (21.4)

1 (2.3)

0 (0)

Not done

6 (13.6)

1 (7.1)

Time to response (weeks)

8.14 weeks (4.1-24.1)

8.14 weeks (7.3-84.1)

Median DOR (weeks) (95% CI)

56.00 weeks (44.43-NE)

NE (6.14-NE)

Median PFS (weeks) (95% CI)

52.00 weeks (16.14-NE)

NE (8.14-NE)

Abbreviations: ORR, objective response rate; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; NE, not evaluable; DOR, duration of response; PFS, progression-free survival
i As assessed by investigator
ii ORR is CR+PR (including uncertified CR [CRu] for ATL)
iii Includes PTCL subtypes: AITL (angioimmunoblastic T-cell lymphoma), PTCL-NOS (not otherwise specified), ALCL (anaplastic large cell lymphoma) and "other" PTCL
iv Median follow-up: 19.93 weeks (range: 3.1-68.1)
v Includes 7 patients with acute and 7 patients with lymphomatous ATL subtypes
vi Median follow-up: 23.07 weeks (range: 3.3-125.0)

About the Phase 1 Study

The open-label, single-arm, multi-center, first-in-human, two-part phase 1 study is evaluating the safety and efficacy of valemetostat in adult patients with relapsed/refractory NHL, including B-cell and T-cell lymphomas. Following the dose escalation portion of the study, which evaluated safety, pharmacokinetics and determined the recommended dose for expansion (200 mg once daily), the dose expansion part enrolled patients into one of two cohorts based on NHL subtype (PTCL and ATL) to further evaluate safety and assess preliminary efficacy. For more information about this study, visit ClinicalTrials.gov.

About VALENTINE-PTCL01 Trial

Data from the phase 1 study of valemetostat presented at EHA (Free EHA Whitepaper) informed the design of the recently initiated pivotal VALENTINE-PTCL01 study. A global, open-label, single-arm, two-cohort phase 2 study, VALENTINE-PTCL01 is evaluating the efficacy and safety of valemetostat in patients with relapsed/refractory PTCL and ATL who have received at least one systemic therapy and are ineligible for HSCT. The first cohort will enroll patients with PTCL, and a second cohort will enroll patients with ATL.

The primary efficacy endpoint of the study is ORR according to blinded independent central review. Secondary efficacy endpoints include CR, PR, DOR, PFS and overall survival. The study will analyze safety endpoints including adverse events as well as pharmacokinetic and exploratory biomarker endpoints. Up to 176 patients will be enrolled at approximately 70 sites in Asia, Europe, North America and Oceania. For more information about this study, visit ClinicalTrials.gov.

About PTCL and ATL

PTCL is a group of rare and heterogenous hematologic malignancies, including ATL, that represent approximately 10-15% of all NHLs.3 Approximately 544,000 new cases of NHL were diagnosed worldwide in 2020.5 There are at least 29 recognized subtypes of PTCL, which occur with significant geographic variation.6 The most common subtypes of PTCL occur frequently in Western countries and in Asia, while ATL is generally more frequent in Japan and parts of the Caribbean and Latin America.7 ATL is associated with the human T-cell lymphotropic virus type 1 (HTLV-1).8

PTCL tends to be aggressive and prognosis is generally poor, with five-year overall survival at 32% in two common PTCLs (PTCL-NOS and AITL) and at 14% for ATL.7 Initial treatment for PTCL is typically a multi-drug chemotherapy-based regimen, and a majority of patients progress with median overall survival of 5.8 months from time of relapse.4 Development of more effective medicines for PTCL and ATL continues to be an unmet clinical need, and one newer area of research and development includes therapeutic targeting of epigenetic changes that contribute to lymphomagenesis.8

About EZH1 and EZH2

EZH1 (enhancer of zeste homolog 1) and EZH2 (enhancer of zeste homolog 2) enzymes are part of polycomb protein complexes and act through histone methylation to regulate expression of genes involved in maintaining hematopoietic stem cells.9 These enzymes are thought to contribute to silencing of genes that suppress tumor cell growth and proliferation.10 EZH1 and EZH2 are recurrently highly expressed or mutated in many hematologic malignancies.10 Research shows that both EZH1 and EZH2 enzymes have a role in hematologic cancer progression and that simultaneous inhibition would be effective in targeting the cancers.1 There are no dual EZH1/2 directed therapies approved for cancer treatment.

About Valemetostat

Valemetostat (DS-3201) is a potential first-in-class, potent and selective small molecule EZH1/2 dual inhibitor currently in clinical development in the Alpha portfolio of Daiichi Sankyo. Valemetostat targets epigenetic regulation by inhibiting both the EZH1 and EZH2 enzymes.

The valemetostat development program includes VALENTINE-PTCL01, a global pivotal phase 2 trial in patients with relapsed/refractory PTCL and ATL; a pivotal phase 2 trial in patients with relapsed or refractory ATL in Japan; a phase 1 study in patients with relapsed/refractory NHL in the U.S. and Japan; and, a phase 1 study in patients with acute lymphocytic leukemia and acute myeloid leukemia in the U.S.

In April 2019, valemetostat received SAKIGAKE Designation for the treatment of adult patients with relapsed or refractory PTCL by the Japan Ministry of Health, Labour and Welfare (MHLW).

Valemetostat is an investigational medicine that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo Oncology

The oncology portfolio of Daiichi Sankyo is powered by our team of world-class scientists that push beyond traditional thinking to create transformative medicines for people with cancer. Anchored by our DXd antibody drug conjugate (ADC) technology, our research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in the U.S. We also work alongside leading academic and business collaborators to further advance the understanding of cancer as Daiichi Sankyo builds towards our ambitious goal of becoming a global leader in oncology by 2025.

Kyowa Kirin welcomes the decision that NICE will revisit their appraisal of the innovative systemic treatment, POTELIGEO®▼ (mogamulizumab), for adults living with two forms of ultra-rare non-Hodgkin lymphoma

On June 11, 2021 Kyowa Kirin reported that The National Institute for Health and Care Excellence (NICE) has upheld an appeal lodged by Kyowa Kirin, Lymphoma Action and Leukaemia Care, and the UK Cutaneous Lymphoma Group (UKCLG) as part of the Single Technology Appraisal for POTELIGEO (mogamulizumab) for the treatment of adults with the ultra-rare blood cancers mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy (Press release, Kyowa Hakko Kirin, JUN 11, 2021, View Source [SID1234583910]).1

The oral appeal hearing took place on 10 May 2021 in front of an independent Appeal Panel appointed by NICE. The Panel heard arguments from representatives of the appellants against the decision not to recommend POTELIGEO, as published in a Final Appraisal Document (FAD) on 4 March 2021.2

The parties involved in the appeal welcome this decision as it represents a significant and positive step forward for the cutaneous T-cell lymphoma (CTCL) community, where there is a high clinical unmet need. Kyowa Kirin remains committed to finding a solution for people living with SS or MF to have access to POTELIGEO and will continue discussions with NICE and NHS England to find a resolution.

Richard Johnson, Northern Cluster General Manager, responsible for the UK at Kyowa Kirin, commented: "The outcome of this appeal is an important step in enabling access to an innovative treatment for people with MF or SS who have few systemic treatment options. We remain committed to working with the patient and clinical community, as appropriate, and we are optimistic that future reconsideration of evidence by the Committee, could resolve the challenges with this appraisal. We strongly believe in the clinical and cost effectiveness of POTELIGEO and will continue a dialogue with NICE and NHS England."

MF and SS are two forms of CTCL3 which is a serious and potentially life-threatening form of cancer.4 Additionally, there is a significant impact on quality of life for those caring for an individual living with CTCL.5 CTCL is treatable but not curable and there is a clear unmet need for new treatment options.

Ropinder Gill, Chief Executive at Lymphoma Action commented: "We’re very grateful and pleased that the NICE Appeal Panel upheld the appeal around mogamulizumab on a number of grounds. This means that by relooking at aspects such as mogamulizumab’s cost effectiveness, there is an opportunity to make this treatment available to those people affected by skin lymphoma who have limited treatment options left. We are hopeful that NICE’s reassessment might bring parity with the SMC’s decision to make mogamulizumab available in Scotland."

About POTELIGEO (mogamulizumab)

Mogamulizumab is a first-in-class humanised monoclonal antibody (mAb) directed against CC chemokine receptor 4 (CCR4), a protein consistently expressed on cancerous cells seen in both MF and SS;6,7,8 once mogamulizumab binds to CCR4, it increases attraction of immune cells from the immune system to destroy the cancerous cells.9

Mogamulizumab has been shown to offer benefits to many patients with MF and SS.10 The MAVORIC trial compared the efficacy of mogamulizumab with vorinostat in previously treated people with relapsed or refractory mycosis fungoides or Sézary syndrome, two types of Cutaneous T-cell lymphoma (CTCL).10 Patients taking mogamulizumab experienced control over their disease for more than twice as long as those taking the comparator treatment, vorinostat*1 (7.7 months vs 3.1 months of median progression free survival), the primary endpoint of the trial.10 Levels of adverse events were similar between the two treatment groups.10 The MAVORIC trial is the largest in CTCL; it enrolled a total of 372 patients across 61 sites in 11 countries (of which 16 sites were in Europe, including three in England).10

About Mycosis Fungoides (MF) and Sézary Syndrome (SS)

MF and SS are characterised by localisation of cancerous white blood cells called T lymphocytes (T cells), to the skin.11,12 These cancerous T cells consistently express a protein called CC-chemokine receptor 4 (CCR4), which enables them to move from the blood to the skin.6,7,8 When these cancerous T cells move to the skin, they can create a localised inflammatory immune skin response, commonly resulting in visible skin symptoms of red patches or plaques 6,13,14,15,16 which can resemble psoriasis or eczema.11

MF and SS can affect the skin, blood, lymph nodes (part of the body’s immune system which is spread throughout the body) and internal organs.17 All four areas of the body are used to assess disease stage,18,19 and clinically significant involvement of the blood, particularly in more advanced disease, is linked with increased morbidity and an overall reduction in patient survival.18,20,21

CTCL can take, on average, between 2 and 7 years for individuals to receive a confirmed diagnosis.22 It is critical for doctors to consider CTCL as an early differential diagnosis as the patient’s prognosis can be affected if the disease progresses to later stages.23 Whilst most individuals that present with early stage disease do not progress to a more severe stage,24 patients with advanced disease have significantly poorer outcomes with only around half of patients (52%) surviving for just 5 years.18

CTCL is a ultra-rare disease that affects 0.7 per 100,000 patients across the UK.25 The annual incidence of MF in Europe is estimated to be between 1 in 110,000 to 1 in 350,000.26 The annual incidence of SS is 1 in 10,000,000.27 Together they represent approximately 65% of all cases of CTCL.17

Imago BioSciences’ Bomedemstat Demonstrates Continued Encouraging Clinical Activity in Phase 2 Data for Treatment of Essential Thrombocythemia and Myelofibrosis at EHA 2021 Virtual Congress

On June 11, 2021 Imago BioSciences, Inc. ("Imago"), a clinical stage biopharmaceutical company discovering new medicines for the treatment of myeloproliferative neoplasms (MPNs), reported updates on two Phase 2 clinical trials of bomedemstat, one in patients with essential thrombocythemia (ET) and, the second in patients with advanced myelofibrosis (MF) (Press release, Imago BioSciences, JUN 11, 2021, View Source [SID1234583909]). The data were presented in two e-poster presentations during the 26th European Hematology Association (EHA) (Free EHA Whitepaper) Virtual Congress (EHA 2021), taking place June 9-17, 2021.

Poster title: A Phase 2 Study of the LSD1 Inhibitor IMG-7289 (Bomedemstat) in Patients with Essential Thrombocythemia

The presented data show that bomedemstat was generally well-tolerated by patients with ET and demonstrated encouraging clinical activity as a monotherapy, showing symptomatic improvement in patients with significant MPN symptoms. Of the 12 patients dosed with bomedemstat for more than six weeks, 83% displayed substantial improvements in platelet count reduction, achieving platelets ≤ 400×109/L. Of the 10 patients entering the study with elevated white blood cell counts and evaluable at 12 weeks, 80% saw these counts fall within normal ranges. These improvements were achieved while maintaining stable hemoglobin levels. There were no dose limiting toxicities, no safety signals per Safety Advisory Board and one serious adverse event that was deemed unrelated.

"These encouraging data show that bomedemstat was well-tolerated and has the potential to bring meaningful clinical benefits for patients with essential thrombocythemia," said Wan-Jen Hong, M.D., chief medical officer of Imago BioSciences. "We are excited about these preliminary results from our lead asset, and look forward to completing enrollment of this study in order to lay the groundwork for a planned pivotal study in essential thrombocythemia."

Poster title: A Phase 2 Study of the LSD1 Inhibitor IMG-7289 (Bomedemstat) in Patients with Advanced Myelofibrosis

The presented data from an ongoing Phase 2 study indicated that bomedemstat as a monotherapy for patients with advanced MF offered a distinct clinical benefit profile, and was generally well-tolerated among participants. Of the 16 patients evaluable at 24 weeks, 94% showed improvements in total symptom scores (TSS), with a reduction of 50% or greater in almost a third of this subset. In an analysis of 34 patients evaluated for mutant allele frequencies (MAFs), MAFs decreased in 44% of patients and were stable in 47%, with no new mutations in up to 660 days of follow-up. Of the 18 patients evaluable for splenomegaly at 24 weeks, 89% had a reduction in spleen volume, with that of one patient decreasing by more than 35%. There were no dose limiting toxicities, no safety signals per Safety Advisory Board, and no progression to acute myeloid leukemia (AML).

"These updated clinical results reveal that bomedemstat continues to offer distinct clinical benefits for patients with advanced MF, showing overall improvement in total symptom scores, spleen volumes and anemia," said Wan-Jen Hong, M.D., chief medical officer of Imago BioSciences. "The study is now fully enrolled, so we look forward to sharing our cumulative data as we continue to advance this investigational program for patients who have few therapeutic alternatives."

Poster presentations are available on the EHA (Free EHA Whitepaper) Virtual Congress platform. The posters will also be available on the Imago website here.

Autolus Therapeutics Presents New Data on obe-cel in r/r Indolent B Cell Lymphomas and gives an update of obe-cel in r/r Adult ALL at the European Hematology Association Virtual Congress

On June 11, 2021 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported a poster presentation related to AUTO1 (obecabtagene autoleucel, obe-cel) in relapsed / refractory (r/r) indolent B cell lymphomas (IBCL) and included an update of duration of response in r/r adult Acute Lymphoblastic Leukemia (ALL) patients at the European Hematology Association (EHA) (Free EHA Whitepaper) Virtual Congress 2021 (Press release, Autolus, JUN 11, 2021, View Source [SID1234583908]).

"The stabilization of event-free survival at 50% between 12 months and 24 months of follow-up supports the curative potential of obe-cel as a standalone therapy for some adult ALL patients," said Dr. Christian Itin, chief executive officer of Autolus. "The early data we presented in indolent B cell non-Hodgkin lymphoma indicate a high level of clinical activity combined with a manageable safety profile and could represent a significant opportunity to expand the benefits of obe-cel treatment to a broader population of patients with B cell malignancies."

Title: Early safety and efficacy findings of AUTO1 (CAT19), a fast-off rate CD19 CAR, in Relapsed/Refractory Indolent B Cell Lymphomas

Presenter: Clare Roddie, MD, PhD, FRCPath, Consultant Haematologist and Honorary Senior Lecturer, Cancer Institute, University College London (UCL)

Session Date and Time: Friday, June 11, 2021 at 9.00 a.m. CEST

Relapsed / refractory (r/r) indolent B cell lymphomas
As of the data cut-off date of May 17, 2021, 13 patients in Cohort D with r/r IBCL had been enrolled in the study and product was successfully manufactured for 12 patients, with one patient’s cells ongoing in manufacture. As of the data cut-off date, 9 r/r IBCL patients had received AUTO1 infusion. Three patients were pending infusion (including the patient noted above) and one patient died prior to lymphodepletion due to a Covid-19 infection. Obe-cel was well tolerated and demonstrated a favorable safety profile in adult patients with r/r low grade B-cell lymphoma, despite high disease burden. All treated patients achieved a complete metabolic remission and had robust CAR T engraftment, expansion, and persistence.

Grade 1 cytokine release syndrome (CRS) was reported in 4 patients and Grade 2 CRS in 1 patient. No immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade was observed in the study. At a median follow-up of 6 months (range 4.0-8.1m), eight of nine patients were disease free at last follow-up with one patient who relapsed at month 6 but was rescued with radiotherapy. One patient died of a COVID-19 infection at month 5.6 whilst in complete metabolic remission.

Relapse / refractory adult Acute Lymphoblastic Leukemia
As of the data cut-off date of May 17, 2021, 20 patients in Cohort A with r/r ALL had received obe-cel. The therapy was well tolerated, with no patients experiencing Grade 3 or higher CRS. Three patients (15%), all of whom had high leukemia burden (>50% blasts), experienced Grade 3 ICANS that resolved swiftly with steroids.

Of the 20 patients evaluable for efficacy, 17 (85%) of patients achieved minimum residual disease (MRD)-negative complete remission (CR) at one month. Most notably, the durability of remissions is highly encouraging. Across all treated patients, event free survival (EFS) at twelve months and twenty-four months is 50.2% with median EFS not being reached.

Conference Call
Management will host a conference call and webcast today at 8:30 am ET/1:30 pm BST to discuss the data presented at EHA (Free EHA Whitepaper). To listen to the webcast and view the accompanying slide presentation, please go to the events section of Autolus’ website.

The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID 3697562. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID 3697562.

Mustang Bio Announces Updated Interim Phase 1/2 Data for MB-106 CD20-Targeted CAR T in Patients with Relapsed or Refractory B-cell Non-Hodgkin Lymphomas and Chronic Lymphocytic Leukemia

On June 11, 2021 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported updated interim data from the ongoing Phase 1/2 clinical trial investigating the safety and efficacy of MB-106 CD20-targeted, autologous CAR T cell therapy for high-risk B-cell non-Hodgkin lymphomas ("B-NHL") and chronic lymphocytic leukemia ("CLL") (Press release, Mustang Bio, JUN 11, 2021, View Source [SID1234583907]). MB-106 is being developed in a collaboration between Mustang and Fred Hutchinson Cancer Research Center ("Fred Hutch").

The data presented in an e-poster session at the European Hematology Association (EHA) (Free EHA Whitepaper) 2021 Virtual Congress ("EHA2021") by Mazyar Shadman, M.D., M.P.H., Associate Professor, Clinical Research Division of Fred Hutch, included safety and efficacy data from the cell manufacturing process that was modified to combine the culture of CD4+ and CD8+ cells. In the 15 patients treated, the overall response rate ("ORR") was 93% (14/15) with a complete response ("CR") rate of 67% (10/15). In 11 patients with follicular lymphoma ("FL"), ORR and CR were 91% (10/11) and 82% (9/11), respectively. As of the time of the e-poster submission to EHA (Free EHA Whitepaper)2021, all patients who achieved CR remained in remission. One patient with FL had an initial partial response with a later disease progression, had a spontaneous CR and remains in remission. The patient with CLL also had a CR and undetectable measurable residual disease in peripheral blood and bone marrow by flow cytometry (10-4) (uMRD4) on day 28. CAR T persistence was seen in all dose levels ("DL") and, while expansion was faster in higher DL, the levels were comparable by day 28.

From a safety profile perspective, cytokine release syndrome ("CRS") occurred in 6 patients (40%): 3 patients with grade 1 and 3 patients with grade 2. Only 1 patient (6.5%) experienced grade 2 immune effector cell-associated neurotoxicity syndrome ("ICANS") and none of the 11 patients with FL experienced ICANS of any grade. No grade 3 or higher CRS or ICANS were seen in any patient.

Dr. Shadman commented, "MB-106 continues to demonstrate a very favorable safety and efficacy profile, as well as sustained complete responses. This compelling clinical activity, including the complete remissions in 67% of the patients in the trial, demonstrates the potential of MB-106 as a viable CD20-targeted CAR T cell therapy. We are pleased that all complete responders continue to remain in remission, and we continue to enroll all eligible CD20+ NHL and CLL patients into this trial."

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "We are encouraged by the updated MB-106 safety and efficacy data presented by Dr. Shadman today. As reported last month, the FDA has accepted Mustang’s IND application to initiate a multicenter Phase 1/2 clinical trial investigating the safety, tolerability and efficacy of MB-106 for relapsed or refractory B-NHL and CLL. We look forward to commencing the trial later this year and further advancing MB-106 for patients with B-NHL and CLL who are in need of new treatment options."

For more information on the clinical trial at Fred Hutch, please visit www.clinicaltrials.gov using the identifier NCT03277729.

Webinar
On Tuesday, June 15, 2021, at 1 p.m. ET, Mustang will host a webinar with Dr. Shadman and colleague Brian Till, M.D., both of Fred Hutch, to discuss the updated interim results from the ongoing Phase 1/2 clinical trial investigating the safety and efficacy of MB-106 CD20-targeted CAR T for B-NHL and CLL. Mustang’s management team will also provide more details on the planned MB-106 Phase 1/2 clinical trial to be conducted under Mustang’s Investigational New Drug ("IND") application. The Company recently announced that the U.S. Food and Drug Administration ("FDA") accepted its IND to initiate a multicenter Phase 1/2 clinical trial investigating the safety, tolerability and efficacy of MB-106 for relapsed or refractory B-NHL and CLL. Following the formal presentations, the Mustang team, along with Drs. Till and Shadman, will be available for questions. To register for the webinar, please click here. An archived replay will be accessible on the Events page of the Investor Relations section of Mustang’s website: www.mustangbio.com for approximately 30 days following the call.

About MB-106 (CD20-targeted CAR T Cell Therapy)
CD20 is a membrane-embedded surface molecule which plays a role in the differentiation of B-cells into plasma cells. The CAR T was developed by Mustang’s research collaborator, Fred Hutch, in the laboratories of the late Oliver Press, M.D., Ph.D., and Brian Till, M.D., Associate Professor in the Clinical Research Division, and exclusively licensed to Mustang in 2017. MB-106 has been optimized as a third-generation CAR derived from a fully human antibody and is currently in a Phase 1/2 open-label, dose-escalation trial at Fred Hutch in patients with B-NHL and CLL. Additional information on the trial can be found at View Source using the identifier NCT03277729.