On December 10, 2023 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported positive final results from the Phase 2 TELLOMAK study in Sézary Syndrome (SS) (Press release, Innate Pharma, DEC 10, 2023, View Source [SID1234638397]). The results were presented at the ASH (Free ASH Whitepaper) 2023 Annual Meeting, in San Diego, California.

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As of May 1, 2023, data cutoff, patients in the Sézary Syndrome cohort (cohort 1, n=56) received a median of 5 prior systemic therapies, including mogamulizumab, and had a median follow-up of 14.4 months.

The data demonstrated that lacutamab showed robust clinical activity and an overall favorable safety profile. The global confirmed objective response rate (ORR) was 37.5% (21/56), including 2 complete responses (CR) and 19 partial responses (PR). Overall response rate (ORR) in the skin was 46.4% (26/56), including 5 CR and 21 PR and ORR in the blood was 48.2% (27/56) with 15 CR and 12 PR. Median progression-free survival was 8.0 months (95% CI 4.7-21.2). In patients who achieved a global response, the median duration of response is 12.3 months (95% CI 5.2-NE).

Best Global Response

N=56

Best Response in Skin

N=56

Best Response in Blood

N=56

Best Response in LN

N=461

Best Response (N, %)

CR

2 (3.6)

5 (8.9)

15 (26.8)

3 (6.5)

PR

19 (33.9)

21 (37.5)

12 (21.4)

6 (13.0)

SD

28 (50.0)

27 (48.2)

24 (42.9)

28 (60.9)

PD

7 (12.5)

3 (5.4)

5 (8.9)

5 (10.9)

NE

0

0

0

4 (8.7)

ORR% [95%CI]

37.5%

[26.0-50.6]

46.4%

[34.0-59.3]

48.2%

[35.7-61.0]

19.6%

[10.7-33.2]

Table 1: Efficacy results in SS patients (n=56)

____________________________________
1 includes patients not involved at baseline who progressed in the LN

"The rapid and durable responses observed in the Phase 2 TELLOMAK trial which enrolled heavily pretreated patients, confirms that treatment with lacutamab achieves clinically meaningful outcomes for patients with Sézary Syndrome after at least two prior systemic therapies," commented Dr. Sonia Quaratino, Chief Medical Officer of Innate Pharma. "Enrollment to TELLOMAK study is completed and long-term follow-up will provide more mature data on the key study endpoints in due course."

Prof. Pierluigi Porcu, Director, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, and Principal Investigator in the TELLOMAK study, added: "Sézary Syndrome patients treated with more than two prior systemic therapies including mogamulizumab, represent a high unmet medical need population with poor quality of life. It is promising to see lacutamab achieving remarkable efficacy along with favorable safety in this heavily pre-treated population. We thank the investigators, clinical research coordinators, patients and caregivers involved in the TELLOMAK program."

Innate Pharma will host a virtual KOL event, featuring Prof. Pierluigi Porcu, on lacutamab, highlighting results from ASH (Free ASH Whitepaper) oral presentation on Tuesday, December 12, 2023 at 7:00AM PST (4:00PM CET).

Virtual KOL Event Details

Tuesday, December 12, 2023 at 7:00 AM PST (4:00PM CET)

The live webcast will be available at the following link:

View Source

Participants may also join via telephone using the following registration link:

View Source

This information can also be found on the Investors section of the Innate Pharma website, www.innate-pharma.com. A replay of the webcast will be available on the Company website for 90 days following the event.

About Lacutamab

Lacutamab is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody that is currently in clinical trials for treatment of cutaneous T-cell lymphoma (CTCL), an orphan disease, and peripheral T cell lymphoma (PTCL). Rare cutaneous lymphomas of T lymphocytes have a poor prognosis with few efficacious and safe therapeutic options at advanced stages.

KIR3DL2 is an inhibitory receptor of the KIR family, expressed by approximately 65% of patients across all CTCL subtypes and expressed by up 90% of patients with certain aggressive CTCL subtypes, in particular, Sézary syndrome. It is expressed by up to 50% of patients with mycosis fungoides and peripheral T-cell lymphoma (PTCL). It has a restricted expression on normal tissues.

Lacutamab is granted European Medicines Agency (EMA) PRIME designation and US Food and Drug Administration (FDA) granted Fast Track designation for the treatment of patients with relapsed or refractory Sézary syndrome who have received at least two prior systemic therapies. Lacutamab is granted orphan drug status in the European Union and in the United States for the treatment of CTCL.

About TELLOMAK

TELLOMAK (NCT03902184) is a global, open-label, multi-cohort Phase 2 clinical trial recruiting patients with Sézary syndrome and mycosis fungoides (MF) in the United States and Europe. Specifically:

Cohort 1: lacutamab being evaluated as a single agent in approximately 60 patients with Sézary syndrome who have received at least two prior systemic therapies, including mogamulizumab. The Sézary syndrome cohort of the study could enable the registration of lacutamab in this indication.
Cohort 2: lacutamab being evaluated as a single agent in patients with MF that express KIR3DL2, as determined at baseline with a Simon 2-stage design.
Cohort 3: lacutamab being evaluated as a single agent in patients with MF that do not express KIR3DL2, as determined at baseline, with a Simon-2 stage design.
All comers: lacutamab being evaluated as a single agent in patients with both KIR3DL2 expressing and non-expressing MF to explore the correlation between the level of KIR3DL2 expression and treatment outcomes utilizing a formalin-fixed paraffin embedded (FFPE) assay under development as a companion diagnostic.
The trial is now fully enrolled. The primary endpoint of the trial is objective global response rate. Key secondary endpoints are progression-free survival, duration of response, overall survival, quality of life, pharmacokinetics and immunogenicity and adverse events.

On December 10, 2023 ImmunoGen Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported new safety and efficacy findings from the newly diagnosed (ND) cohorts of the Phase 1b/2 study of pivekimab sunirine (pivekimab) in combination with azacitidine (Vidaza) and venetoclax (Venclexta), (pivekimab triplet) in patients with ND acute myeloid leukemia (AML) (Press release, ImmunoGen, DEC 10, 2023, View Source [SID1234638396]). These findings will be presented in a poster session at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California.

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"Building upon our initial findings in frontline AML presented last year, these data show broad and consistent response rates in a larger study population and across major molecular subsets of interest, including those patients with biological mutations making them high-risk"

Post this
"We are pleased to share these new findings at ASH (Free ASH Whitepaper), which demonstrate encouraging anti-leukemia activity of the pivekimab triplet in newly diagnosed AML, a disease in which long-term survival unfortunately remains limited," said Naval Daver, MD, Associate Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. "The MRD negativity rates, which are indicative of a deep remission, are particularly promising in the treated patient population. This encouraging activity, along with a manageable safety profile, support the continued evaluation of this novel triplet in this setting."

PIVEKIMAB SUNIRINE, A CD123-TARGETING ANTIBODY-DRUG CONJUGATE, IN COMBINATION WITH AZACITIDINE AND VENETOCLAX IN PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA
Lead Author: Navel Daver, MD
Poster Session: 616 (Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II)
Date and Time: Sunday, December 10, 2023, 6:00-8:00 p.m. PT / 9:00-11:00 p.m. ET
Publication Number: 2906

In the open-label, multicenter, Phase 1b/2 study of pivekimab in combination with azacitidine and venetoclax in patients with ND CD123-positive AML, patients received the recommended Phase 2 dose of pivekimab at 0.045 mg/kg on day 7, azacitidine at 75 mg/m2 daily on days 1-7, and venetoclax at up to 400 mg for at least 14 days or up to 28 days, based on cohort assignment, in a 28-day cycle. The primary endpoints are complete remission (CR) rate, composite CR rate (CCR [CR+CRh+CRp+CRi]), minimal residual disease (MRD) negativity rate, and duration of remission. Key secondary endpoints are safety, pharmacokinetics, and immunogenicity.

Key findings for 50 ND patients (n=25 per cohort) as of September 29, 2023 (data cut-off) include:

Anti-Leukemia Activity

In the overall population, CCR rate was 68% (34/50), CR rate was 54% (27/50), and MRD negativity rate among evaluable patients achieving CCR was 76% (22/29). MRD was assessed centrally by flow cytometry with <0.1% considered negative. Response rates and MRD negativity were numerically comparable between cohorts 1 and 2, despite differences in the venetoclax schedule.
In a post hoc subset analysis of patients unfit for intensive chemotherapy (i.e. patients >75 years of age, and/or with pre-specified comorbidities) (n=23), CCR rate was 78% (18/23), CR rate was 61% (14/23), and MRD negativity rate was 79% (11/14).
In patients known to be TP53wt (n=25), CCR rate was 88% (22/25), CR rate was 84% (21/25), and MRD negativity rate was 80% (16/20). CCR and MRD negativity rates, respectively, were high across other major molecular subsets, including:
FLT3 (ITD or TKD): 100% (6/6) and 100% (6/6)
IDH1 mutant: 100% (4/4) and 67% (2/3)
IDH2 mutant: 100% (6/6) and 83% (5/6)
NPM1 mutant: 100% (8/8) and 86% (6/7)
K/NRAS mutant: 50% (3/6) and 67% (2/3)
TP53 mutant: 50% (7/14) and 50% (3/6)
Among all MRD negative patients, the median time to MRD negativity was 1.87 months (range: 0.79-5.16 months).
Although follow-up duration was short (median 5.2 months), landmark overall survival estimate at 6 months is 86%.
The study is continuing to enroll newly diagnosed unfit AML patients.
Safety

The triplet displayed a manageable safety profile; no new safety signals were observed compared to previously reported data.
The most common non-hematologic treatment-emergent adverse events (TEAEs) (all grades [grade 3+]) seen in ≥20% of all patients were constipation (48% [2%]), peripheral edema (44% [4%]), diarrhea (40% [2%]), hypophosphatemia (34% [2%]), nausea (32% [4%]), hypokalemia (28% [4%]), fatigue (24% [6%]), hypotension (24% [2%]), and pyrexia (24% [0%]). In the overall population:
Rates of cytopenias were similar to those observed with azacitidine and venetoclax, with a median neutrophil recovery to ≥500/µL and platelet recovery to ≥50,000/µL by day 34 and day 22, respectively.
No veno-occlusive disease, capillary leak syndrome, or sinusoidal obstruction syndrome were observed.
Infusion-related reactions (IRRs) occurred in 16% of patients (0 grade 3+ IRRs).
Discontinuations due to an adverse event (AE) were 4% (2 patients).
30-day mortality was 0%.
60-day mortality was 4% (2 patients; due to pneumonia and early disease progression).
"Building upon our initial findings in frontline AML presented last year, these data show broad and consistent response rates in a larger study population and across major molecular subsets of interest, including those patients with biological mutations making them high-risk," said Michael Vasconcelles, MD, ImmunoGen’s Executive Vice President, Research, Development, and Medical Affairs. "We are pleased with the low early mortality and manageable safety profile observed, in particular the lack of prolonged cytopenias. We look forward to continuing to expand our cohort of newly diagnosed unfit patients to inform the development path for pivekimab in AML."

PRECLINICAL POSTERS
ImmunoGen is also presenting two preclinical posters at ASH (Free ASH Whitepaper).

Title: Venetoclax Synergizes with IMGN632, a Novel CD123-Targeting Antibody Conjugated to a DNA Alkylating Payload, By Suppressing DNA Damage Response and Potentiating Apoptosis in Acute Myeloid Leukemia in Vitro Models
Presenter: Anna Skwarska
Session: 604 (Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster III)
Date and Time: Monday, December 11, 2023, 6:00-8:00 p.m. PT / 9:00-11:00 p.m. ET
Publication Number: 4155

Title: Spatial Response to Pivekimab Sunirine In Vivo in a BPDCN Model
Presenter: Margaux Poussard
Session: 604 (Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster II)
Date and Time: Sunday, December 10, 2023, 6:00-8:00 p.m. PT / 9:00-11:00 p.m. ET
Publication Number: 2791

Additional information can be found at View Source, including abstracts.

ABOUT PIVEKIMAB SUNIRINE
Pivekimab sunirine is a CD123-targeting ADC in clinical development for hematological malignancies, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), and other CD123+ hematologic malignancies. Pivekimab is currently being evaluated as monotherapy for patients with BPDCN and in combination with azacitidine (Vidaza) and venetoclax (Venclexta) for patients with untreated and relapsed/refractory AML. Pivekimab uses one of ImmunoGen’s novel indolinobenzodiazepine (IGN) payloads, which alkylate DNA and cause single-strand breaks without crosslinking. IGNs are designed to have high potency against tumor cells, while demonstrating less toxicity to normal marrow progenitors than other DNA-targeting payloads. The European Medicines Agency (EMA) granted orphan drug designation to pivekimab for the treatment of BPDCN in June 2020. Pivekimab also holds this designation in the US. In October 2020, the FDA granted pivekimab Breakthrough Therapy designation in relapsed/refractory BPDCN.

ABOUT ACUTE MYELOID LEUKEMIA (AML)
AML is a cancer of the bone marrow cells that produce white blood cells. It causes the marrow to increasingly generate abnormal, immature white blood cells (blasts) that do not mature into effective infection-fighting cells. The blasts quickly fill the bone marrow, impacting the production of normal platelets and red blood cells. The resulting deficiencies in normal blood cells leave the patient vulnerable to infections, bleeding problems, and anemia. It is estimated that, in the US alone, more than 20,000 people will be diagnosed with AML and more than 11,000 will die from the disease this year.

ABOUT CD123
CD123, the interleukin-3 alpha chain, is expressed on multiple myeloid and lymphoid cancers including AML, BPDCN, ALL, chronic myeloid leukemia, and myeloproliferative neoplasms. With limited expression on normal hematopoietic cells, rapid internalization, and expression on AML leukemia stem cells, CD123 is a clinically validated therapeutic target.

On December 10, 2023 Schrödinger (Nasdaq: SDGR), whose physics-based computational platform is transforming the way therapeutics and materials are discovered, reported new preclinical data on SGR-1505, its investigational MALT1 inhibitor, and SGR-2921, its investigational CDC7 inhibitor, in a poster session at the American Society of Hematology (ASH) (Free ASH Whitepaper) 65th Annual Meeting taking place virtually and in San Diego, California (Press release, Schrodinger, DEC 10, 2023, View Source [SID1234638395]). The preclinical data reported show that both SGR-1505 and SGR-2921 have multiple favorable attributes and the potential for combination activity with standard-of-care agents.

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Schrödinger also reported preliminary pharmacodynamic data from the Phase 1 study of SGR-1505 in healthy subjects, which showed that SGR-1505 inhibited cytokine release in human whole blood and demonstrated evidence of MALT1 inhibition in humans. The company will report additional data from the healthy subject study at its Pipeline Day on December 14, 2023.

"The pharmacological data for SGR-1505 and SGR-2921 demonstrate that our development candidates have favorable, differentiated profiles with best-in-class potential," stated Karen Akinsanya, Ph.D., president of R&D therapeutics at Schrödinger. "Our progress within these programs further validates our computational approach to designing therapies with the potential to address the limitations of current treatments. SGR-1505 and SGR-2921 are now being evaluated in Phase 1 clinical studies, and we look forward to seeing these programs advance."

A Phase 1 dose-escalation study of SGR-1505 in relapsed or refractory B-cell malignancy patients is ongoing in the U.S. and Europe. Additionally, a Phase 1 clinical study of SGR-2921 was recently initiated in patients with acute myeloid leukemia or myelodysplastic syndrome. Both studies are designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and determine the recommended dose for further development.

SGR-1505 Data at ASH (Free ASH Whitepaper)

The presentation (Abstract # 2997), "SGR-1505 is a Potent MALT1 Protease Inhibitor with a Potential Best-in-Class Profile," includes preclinical data demonstrating the potency of SGR-1505 and the potential for combination activity with standard of care agents. Preclinical data showed that SGR-1505 is more potent than JNJ-6633, which has previously provided clinical validation for MALT1 inhibition as a potential therapeutic strategy for treating both chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphomas (NHL). In a preclinical model of diffuse large B-cell lymphoma, SGR-1505, in combination with venetoclax, demonstrated a stronger combination impact on cell viability compared to JNJ-633 plus venetoclax. Gene expression analysis showed that SGR-1505 provides greater modulation of NF-ΚΒ and related pathway genes compared to JNJ-6633. Signaling of the NF-ΚΒ pathway is known to play a critical role in the initiation and progression of many types of cancers, particularly B cell malignancies.

Preliminary clinical biomarker data from the Phase 1 study in healthy subjects showed that SGR-1505 inhibited cytokine release in ex vivo stimulation of human whole blood. The inhibition of certain cytokines in whole blood from human subjects dosed with SGR-1505 provides pharmacodynamic evidence of MALT1 inhibition. These data are consistent with prior preclinical observations in an in vitro whole blood assay from healthy human subjects, where approximately a 50-fold lower concentration of SGR-1505 was needed to achieve 90 percent inhibition of cytokine release compared to JNJ-6633. The data support continued evaluation of SGR-1505 in the ongoing Phase 1 study in patients with advanced B-cell malignancies.

SGR-2921 Data at ASH (Free ASH Whitepaper)

The presentation (Abstract #2801), "SGR-2921, a Potent CDC7 Inhibitor, Demonstrates Significant Anti-Leukemic Responses in Patient-Derived AML Models Representing Difficult-to-Treat Disease," includes preclinical data for SGR-2921 which demonstrate the potency, breadth of activity and synergistic effects of SGR-2921 in combination with standard-of-care therapies. In vitro, SGR-2921 exhibited greater potency compared to other clinical-stage CDC7 inhibitors and showed anti-proliferative activity in AML patient-derived samples regardless of driver mutations. In vivo, SGR-2921 showed dose-dependent reduction of AML blasts in multiple AML models representing difficult-to-treat disease. SGR-2921 also showed synergistic activity in combination with decitabine in p53-mutated AML models in vivo. Together, these data support the ongoing evaluation of SGR-2921 as a potential treatment for AML, with particular utility in patients with high-risk mutations and relapsed and refractory AML.

Schrödinger Pipeline Day Webcast Information

Schrödinger will review the company’s proprietary research and development programs, including updates on SGR-1505 and SGR-2921, at its Pipeline Day taking place in-person and virtually on December 14, 2023. Pipeline Day will be a hybrid event, with a webcast and limited in-person attendance available to members of the investment community. The presentation can be accessed in the "Investors" section of Schrödinger’s website and will be archived for approximately 90 days. To participate in the live webcast, please register for the event here. It is recommended that participants register at least 15 minutes in advance of the event.

On December 10, 2023 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for cancer, reported that an abstract outlining PK and PD profiling data from the Company’s ongoing Phase 1 study of ADI-001 for the potential treatment of relapsed or refractory aggressive B-cell NHL was made available as part of the 65th ASH (Free ASH Whitepaper) Annual Meeting, being held December 9-12, 2023 in San Diego, California (Press release, Adicet Bio, DEC 10, 2023, View Source [SID1234638394]). The data will be provided during a poster presentation at the ASH (Free ASH Whitepaper) Annual Meeting on Sunday, December 10, 2023.

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"We are pleased to share encouraging observations from the pharmacokinetic and pharmacodynamic analyses of ADI-001 at ASH (Free ASH Whitepaper), further characterizing its potential as a best-in-class allogeneic CAR T platform. The data presented today showed dose-dependent expansion and persistence that met or exceeded that in prescribing information of approved autologous CD19 CAR T therapies, supporting ADI-001’s potential as an effective therapeutic option for patients with advanced cancers," said Francesco Galimi, M.D., Ph.D., Chief Medical Officer. "Historically, expansion and persistence of cell therapy products and release of functional cytokines have correlated with patient outcomes. We remain on track to provide a clinical update from the Phase 1 study in NHL patients in the second half of 2024."

Data highlights included in the ASH (Free ASH Whitepaper) presentation were as follows:

Robust dose-dependent expansion and persistence of ADI-001 were observed using three different methodologies for measuring exposure.
ADI-001 displayed a strong exposure profile and was positively associated with both PD correlates and clinical response, as supported by the following:
At DL3 and DL4, ADI-001 Cmax and Tmax that met or exceeded that in prescribing information of approved autologous CD19 CAR T therapies.
Increasing dose levels showed higher Cmax and AUC and were associated with patient clinical responses.
ADI-001 stimulation and proliferation were associated with peak levels of CAR+ cells and higher production of polyfunctional cytokines, particularly in patients whose best overall response was complete response or partial response.
Elevating levels of endogenous cytokines, comprising stem cell factor and IL-15, may potentially contribute to increased ADI-001 expansion and clinical response.
ADI-001 exposure or clinical response showed no correlation with the degree of shared HLA alleles between patient and ADI-001.
Details of the poster presentation are as follows:

Title: Expansion, Persistence and Pharmacodynamic Profile of ADI-001, a First-in-Class Allogeneic CD20-Targeted CAR Gamma Delta T Cell Therapy, in Patients with Relapsed/Refractory Aggressive B-Cell Non-Hodgkin’s Lymphoma
Poster Number: 3478
Session Name: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster II
Presenting Author: Monica Moreno, Ph.D.
Date/Time: Sunday, December 10, 2023, from 6:00 – 8:00 p.m. PST
About ADI-001

ADI-001 is an investigational allogeneic gamma delta CAR T cell therapy being developed as a potential treatment for relapsed or refractory B-cell NHL. ADI-001 targets malignant B-cells via an anti-CD20 CAR and via the gamma delta innate and T cell endogenous cytotoxicity receptors. Gamma delta T cells engineered with an anti-CD20 CAR have demonstrated potent antitumor activity in preclinical models, leading to long-term control of tumor growth. ADI-001 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the potential treatment of relapsed or refractory B-cell NHL.

About the GLEAN Study

The Phase 1 study is an open-label, multi-center study of ADI-001 enrolling adults diagnosed with B-cell malignancies who have either relapsed, or are refractory to, at least two prior regimens. The primary objectives of the study are to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ADI-001, and to determine optimal dosing as a monotherapy. For more information about the clinical study design, please visit www.clinicaltrials.gov (NCT04735471).

On December 10, 2023 Be Biopharma, Inc. ("Be Bio"), a company pioneering the discovery and development of Engineered B Cell Medicines (BCMs), reported results from a new preclinical study demonstrating that the company’s novel engineered BCM, BE-101, produces active and sustained levels of Factor IX (FIX) for the treatment of hemophilia B (Press release, Be Biopharma, DEC 10, 2023, View Source [SID1234638393]).​ These data were shared during an oral presentation at the 65th annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) taking place in San Diego, California. Also today, Be Bio announced plans to advance BE-101 as its lead program for the treatment of people with severe or moderately severe hemophilia B.​

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In addition, the company announced the appointment of Glenn Pierce, M.D., Ph.D., globally renowned hemophilia physician-researcher, as a member of the Be Bio Scientific Advisory Board.

"The preclinical study findings presented today demonstrate that BE-101 can produce predictable, persistent FIX activity levels with the potential to prevent bleeding and joint damage in persons with hemophilia B," said Richard A. Morgan, Ph.D., chief scientific officer, Be Bio. "We are excited by these findings as we advance this novel BCM into clinical development to address enduring unmet medical needs for people living with hemophilia B. Our data demonstrate that a single dose of BE-101 allows for sustainable, steady-state FIX levels, making it a potentially transformative FIX replacement option for adults and children with hemophilia B."​

"Despite several major advances in treatment options for people with hemophilia B, including extended-release recombinant factor IX biologics and the availability of a new gene therapy, significant unmet needs remain for people living with hemophilia B. Many people living with hemophilia B still experience bleeding episodes, irreversible joint damage and pain with current extended-release factor IX biologic therapy. A redosable treatment that can provide sustained therapeutic levels of FIX has the potential to prevent irreversible joint damage before it occurs, which could be a major therapeutic advance for adults and importantly, children living with hemophilia B," Dr. Pierce said.

"Our goal is to create a new, potentially transformative treatment option that will provide people with hemophilia B the freedom to live a normal life, free of limitations from hemophilia B. We look forward to filing our Investigational New Drug application for BE-101 in mid-2024​," said Joanne Smith-Farrell, Ph.D., chief executive officer, Be Bio. ​"As we announce our lead program in hemophilia B, we are delighted to welcome Dr. Pierce to our Scientific Advisory Board," Smith-Farrell said. "Dr. Pierce is a tireless patient advocate, hemophilia survivor, biotechnology industry leader, and deeply respected hematology thought leader. All of us at Be Bio are inspired by the opportunity to advance BE-101 as the first program in a bold new class of cell therapies with the potential to transform care for people living with serious disease."

Dr. Pierce has more than 30 years of experience in biopharmaceutical research and development and has been involved in the development and approval of six hemophilia therapies. He currently serves on the World Federation of Hemophilia (WFH) Vice President Medical and WFH USA Board of Directors and the U.S. Medical and Scientific Advisory Council of the National Bleeding Disorders Foundation. The co-author of more than 200 scientific papers, Dr. Pierce also served on the Blood Products Advisory Committee of the U.S. Food and Drug Administration and the Committee on Blood Safety and Availability of the US Department of Health and Human Services.

BE-101 Oral Presentation at American Society of Hematology (ASH) (Free ASH Whitepaper)

Poster Title: "Development of an Ex Vivo Precision Gene Engineered B Cell Medicine That Produces Active and Sustained Levels of FIX for the Treatment of Hemophilia B"
Presentation #: 463
Oral Presentation Session: 703. Cellular Immunotherapies: Basic and Translational: Novel Approaches for Next Generation Cellular Immunotherapies
Date/Time: Sunday, December 10, 9:30am PT
Presenter: Richard A. Morgan, Ph.D., Chief Scientific Officer, Be Bio

Study Summary

In this study, primary human B cells were isolated and engineered by CRISPR/Cas9 genome editing followed by AAV-mediated homology directed repair (HDR) insertion of human FIX gene into the CCR5 safe harbor locus. The cells were then further expanded and differentiated toward the plasma cell lineage, resulting in FIX-producing BCMs. Approximately 50% targeted integration was achieved, as measured by droplet digital PCR (ddPCR). Engineered BCMs secreted up to 60 ng/1e6 cells/hour of FIX protein, approaching 40% of IgG secretion rate as measured by ELISA. Vitamin K-dependent activated partial thromboplastin time (aPTT), using the one stage clotting assay, demonstrated biological activity of BCM-produced FIX. Similarly, FIX-expressing BCMs exhibited vitamin K-dependent activity in vitro in the chromogenic assay. FIX-expressing BCMs were transferred into immunodeficient NOG-hIL6 mice, with stable FIX production demonstrated for >168 days in vivo. Redosability was demonstrated with increased engraftment (measured by human IgG levels) and a concomitant increase in plasma FIX. The safety of FIX-expressing BCMs has been characterized based on 28-day and 5-month in vivo studies in NOG-hIL6 mice (n=168 mice). Neither abnormal clinical observations nor mortality were observed in those studies. Biodistribution of the FIX-expressing BCMs was assessed using qPCR. The data confirmed the expected biodistribution of FIX-expressing BCMs in bone marrow tissue, where they engraft stably over time.

About Hemophilia B

Hemophilia B is an X-linked recessive bleeding disorder that affects approximately 1:20,000 males. It is caused by mutations in the gene that encodes for the FIX protein, an essential enzyme in the coagulation cascade. This can lead to spontaneous bleeding as well as bleeding following injuries or surgery.1 People with hemophilia B bleed longer than other people. Bleeds can occur internally, into joints and muscles, or externally, from minor cuts, dental procedures or trauma.2 While an adeno-associated virus (AAV) vector-based gene therapy has been approved for some adults as a potential new option, the current standard of care and only treatment for children remains prophylactic administration of exogenous FIX derived from recombinant protein. The short biological half-life of FIX requires frequent infusions to maintain therapeutic levels.

About Engineered B Cell Medicines – A New Class of Cellular Medicines

Imagine what could "Be?" In nature, a single B cell engrafts in the bone marrow and can produce thousands of proteins per second at constant levels over decades. B cells are nature’s exquisite medicine factories, manufacturing proteins to fight disease and maintain health. Unleashing the power of B cells is driving a new class of cellular medicines – Engineered B Cell Medicines (BCMs). BCMs have the potential to be durable, allogeneic, redosable and administered without toxic conditioning. The promise of BCMs could transform therapeutic biologics with broad application — across protein classes, patient populations and therapeutic areas.