On December 9, 2024 MaaT Pharma (EURONEXT: MAAT – the "Company"), a clinical-stage biotechnology company and a leader in the development of Microbiome Ecosystem TherapiesTM (MET) dedicated to enhancing survival for patients with cancer through immune modulation, reported that Prof. Malard, MD, hematology professor at Saint-Antoine Hospital and Sorbonne University, detailed updated data for 154 patients with acute Graft-versus-Host Disease (aGvHD) treated with MaaT013 in Early Access Program (EAP) in Europe during the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, MaaT Pharma, DEC 9, 2024, View Source [SID1234648907]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Speaking on the data, Florent Malard, MD, PhD, highlighted: "These findings underscore MaaT013’s potential as a transformative therapy for aGvHD, a condition with poor survival rates and limited treatment options. The high response rates and long-term survival data further validate the critical role of the gut microbiome modulation in managing aGvHD. Additionally, these results highlight the growing interest within the medical community, as demonstrated by ASH (Free ASH Whitepaper)’s dedicated symposium on the microbiome’s role in transplantation and cellular therapies."

Hervé Affagard, CEO and co-founder of MaaT Pharma, added: "The high demand from clinicians demonstrates growing adoption and trust in MaaT013. The strong real-world data from our Early Access Program not only gives us confidence as we approach Phase 3 results but also validates our immune modulation approach through microbiome-based therapies. Success in GvHD, a severe and complex immune-mediated disease, would pave the way to demonstrate the platform’s potential to address a broad range of complex immune-related diseases."

As a reminder, key findings include:

For the full cohort (154 patients) in the EAP

Durable reponse: 51% GI-ORR at Day 28 and a 44% GI-ORR at Day 56. ORR for all organs was 49% at D28 and 42% at D56.
Overall survival (OS): 53% at 6 months, 47% at 12 months, and 42% at 24 months.
Median survival follow-up: 418 days (range, 27-1644 days).
Subset (n=58) resembling the population enrolled in the Phase 3 ARES trial (receiving 2nd line ruxolitinib):

Higher response rate than the full cohort: GI-ORR was 59% at Day 28 and 54% at D56. ORR considering all organ was 55% at D28, and 56% at D56.
OS was 54% at 6 months, 49% at 12 months, and 40% at 24 months vs 15% at 12 months in published historical data (Abedin et al. Br J Haematol. 2021 Nov).

On December 9, 2024 Kura Oncology, Inc. (Nasdaq: KURA, "Kura") and Kyowa Kirin Co., Ltd. (TSE: 4151, "Kyowa Kirin") reported encouraging clinical data from KOMET-007, a Phase 1 dose-escalation trial of ziftomenib, a highly selective oral investigational menin inhibitor, in combination with standards of care, including cytarabine/daunorubicin (7+3) and venetoclax/azacitidine (ven/aza), in patients with NPM1-mutant (NPM1-m) and KMT2A-rearranged (KMT2A-r) acute myeloid leukemia (AML) (Press release, Kyowa Hakko Kirin, DEC 9, 2024, View Source [SID1234648906]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

These data were presented at the 2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. An oral presentation highlighting ziftomenib combined with 7+3 in newly diagnosed (1L) NPM1-m and KMT2A-r adverse riski AML, and a poster featuring ziftomenib in combination with ven/aza in relapsed/refractory (R/R) NPM1-m and KMT2A-r AML are available in the Posters and Presentations section on Kura’s website.

Ziftomenib was generally well tolerated in combination at all dose levels evaluated across all cohorts in the Phase 1a dose-escalation portion of the study. No dose-limiting toxicities, evidence of ziftomenib-associated QTc prolongation, drug-drug interactions or additive myelosuppression were observed. In the 7+3 combination cohorts, on-target differentiation syndrome (DS) occurred in 2% (1/51) of patients. Grade ≥3 treatment emergent adverse events occurring in ≥20% were febrile neutropenia platelet count decreased, anemia and neutropenia count decrease and white blood cell count decreased. In the ven/aza combination cohorts, on-target DS occurred in 8% (4/53) of patients. Grade ≥3 treatment emergent adverse events occurring in ≥20% were platelet count decreased, anemia and febrile neutropenia. All instances of DS were manageable, and no patients discontinued participation due to DS. The Phase 1b expansion portion of KOMET-007 is now enrolling at 600 mg in all cohorts, including patients with 1L NPM1-m or KMT2A-r AML in combination with ven/aza.

Among the response-evaluable patients enrolled in the 7+3 combination cohort for patients with 1L NPM1-m or KMT2A-r adverse riski AML, 91% (42/46) achieved a complete remission (CR) (100% for NPM1-m, 83% for KMT2A-r patients). MRD negativity was 76% in NPM1-m and 75% in KMT2A-r patients. All NPM1-m patients (24/24) and 96% (26/27) of KMT2A-r patients remained alive as of the data cutoff on October 1, 2024, with a median follow-up of 31 and 19 weeks, respectively.

A total of 54 patients were enrolled in the combination cohort with ven/aza in R/R NPM1-m or KMT2A-r AML. The NPM1-m population achieved an overall response rate (ORR) of 68% (15/22) and a composite complete remission (CRc) rate of 50% (11/22). In NPM1-m patients with previous ven exposure, ORR was 50% (7/14) and CRc was 36% (5/14). In KMT2A-r patients, 30% of patients responded, including those with prior ven exposure.

"The findings presented at ASH (Free ASH Whitepaper) underscore the potential of ziftomenib in combination with standards of care as an early intervention in the frontline setting of AML and could offer a meaningful opportunity to improve patient outcomes," said Amer Zeidan, MBBS, MHS, chief of the Division of Hematologic Malignancies, director of Hematology Early Therapeutics Research at Yale Cancer Center, and lead investigator of the KOMET-007 trial. "The high rates of complete remission and MRD negativity across the 7+3 cohorts are particularly encouraging. The rapid enrollment in the Phase 1a portion of this study underscores the urgency and enthusiasm for further evaluating this combination approach."

Kura and Kyowa Kirin recently announced plans for KOMET-017, a global, pivotal Phase 3 study evaluating ziftomenib in combination with standards of care for adults with newly diagnosed KMT2A-r or NPM1-m AML. The trial includes two independently powered, randomized, double-blind, placebo-controlled studies: a non-intensive therapy arm testing ziftomenib with ven/aza, and an intensive therapy arm testing ziftomenib with 7+3. The positive results from KOMET-007 reported at ASH (Free ASH Whitepaper) reinforce Kura’s and Kyowa Kirin’s commitment to evaluating ziftomenib for patients across the continuum of frontline treatment options. The KOMET-017 study is expected to initiate in mid-2025.

"Starting patients on therapy early is essential to improving outcomes in AML," said Mollie Leoni, M.D., Executive Vice President, Clinical Development at Kura Oncology. "The updated KOMET-007 data underscore the combination potential of ziftomenib in the frontline setting, strengthening our confidence in its ability to provide a valuable treatment option for a significant portion of the AML population. Together, the KOMET-007 Phase 1b trial and the KOMET-017 pivotal Phase 3 study will allow us to further explore this approach and the potential to transform care if approved for AML patients worldwide."

"More than half of AML patients with an NPM1 mutation will relapse with poor survival outcomesii, making it a significant area of unmet medical need in the frontline setting," said Takeyoshi Yamashita, Ph.D., Senior Managing Executive Officer and Chief Medical Officer of Kyowa Kirin. "The data observed to date represent the potential of ziftomenib to help address the treatment gap and improve upon current standards of care. Leveraging our hemato-oncology expertise and commitment to patients, we are committed to rapidly advancing the clinical development of ziftomenib."

Virtual Investor Event

Kura will host a webcast and conference call featuring Kura Oncology management and Key Opinion Leaders Amir T. Fathi, MD, Associate Professor of Medicine at Harvard Medical School and Director of the Leukemia Program at Massachusetts General Cancer Center, and Amer Zeidan, MBBS, MHS, interim chief of the Division of Hematologic Malignancies, Director of Hematology Early Therapeutics Research at Yale Cancer Center. The live call may be accessed by dialing (800) 715-9871 for domestic callers and (646) 307-1963 for international callers and entering the conference ID: 4326549. A live webcast will be available here and in the Investors section of Kura’s website, with an archived replay available shortly after the event.

About Ziftomenib

Ziftomenib is a selective and oral menin inhibitor currently in development for the treatment of genetically defined AML patients with high unmet need. In April 2024, ziftomenib received Breakthrough Therapy Designation (BTD) by the FDA for the treatment of R/R NPM1-mutant AML based on data from Kura’s ongoing KOMET-001 clinical trial. Additional information about clinical trials for ziftomenib can be found at kuraoncology.com/clinical-trials/#ziftomenib.

On December 9, 2024 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported new data highlighting the quality-of-life improvements observed in patients with cutaneous T-cell lymphoma (CTCL) treated with lacutamab in the TELLOMAK Phase 2 clinical study (Press release, Innate Pharma, DEC 9, 2024, View Source [SID1234648905]). These data were presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The TELLOMAK study addresses a critical unmet need for patients with advanced-stage CTCL, particularly Sézary syndrome (SS) and mycosis fungoides (MF), who often experience debilitating symptoms such as severe itching and recurrent skin infections that profoundly impact their physical and social well-being.

Patients with relapsed or refractory CTCL face limited treatment options and often report lower health-related quality of life, particularly those in advanced stages. TELLOMAK’s findings reveal promising signs that lacutamab may help alleviate some of the most distressing symptoms of this disease early on treatment. The TELLOMAK trial enrolled 163 patients with advanced CTCL, including 56 with SS and 107 with MF. The study’s quality of life measures included the Visual Analogue Scale (VAS) for itch intensity and the Skindex-29 score, a validated tool for assessing the impact of skin conditions on patient quality of life.

"These findings underscore the potential of lacutamab for patients with advanced CTCL, particularly Sézary syndrome and mycosis fungoides, who face severe symptoms and limited treatment options. The promising results, including sustained itch reduction and improved skin symptoms, offer hope for enhancing quality of life. We are excited about lacutamab’s potential to bring meaningful relief to patients enduring this challenging disease," commented Dr Pierluigi Porcu, Director, Division of Medical Oncology and Hematopoietic Stem Cell Transplantation Thomas Jefferson University, and principal investigator in the TELLOMAK study.

"We are encouraged by the data showing that lacutamab may help alleviate some of the most distressing symptoms of cutaneous T cell lymphomas. We remain committed to bringing lacutamab to patients in need and we remain focused on exploring all pathways forward to ensure this potential treatment reaches those who could benefit from it. Our dedication to addressing the unmet needs of patients continues to drive our efforts," added Dr Sonia Quaratino, Chief Medical Officer of Innate Pharma.

Health-related quality of life findings from the TELLOMAK Phase 2 study

Sézary Syndrome Patients (n=56)

•Patient Profile: Median age of 69, advanced disease (67.9% with erythema covering over 80% body surface area), and a median of five prior systemic therapies, high score of pruritus (VAS 6.2) and severe Skindex-29 score (52.7) at baseline.

•Improvement in Itch intensity: From Week 5, patients experienced a reduction in itch intensity, with a clinically significant 2-point decrease on the VAS scale to mild by Week 13 (VAS<4), which was sustained over time.

•Reduction in Skin-Related Symptoms: Patients reported notable improvements on the Skindex-29 scale, beginning as early as Week 5 (Skindex 38.7). Scores continued to decrease to mild then low score (Skindex 27.8 by Week 13 and Skindex 14.4 by Week 45), indicating sustained improvements in skin-related symptoms over time.

Mycosis Fungoides Patients (n=107)

•Patient Profile: Median age of 62, less advanced disease (15.9% T4 stage), and a median of four prior systemic therapies, high score of pruritus (VAS 6) and severe Skindex-29 score (56.3) at baseline.

•Improvement in Itch intensity: from Week 5 (VAS 5), with a deeper improvement observed from Week 37 (<4) onward.

•Reduction in Skin-Related Symptoms: Skindex-29 scores also showed early reductions from Week 5 with less severe score (Skindex 46.3), with more pronounced decreases to moderate score by Week 29 (Skindex 38.8) then low score, reflecting gradual yet meaningful improvement in symptoms affecting daily life.

Translational analysis of the TELLOMAK Phase 2 study.

In addition, data on the translational analysis from the study in patients with R/R Sézary Syndrome were presented at the 66th ASH (Free ASH Whitepaper) Annual Meeting.

The results show lacutamab induced early and deep depletion of KIR3DL2-expressing circulating tumor cells (CTCs) irrespective of the baseline blood tumor burden. Blood response correlated with the percentage of KIR3DL2 expression on CTCs. In addition, lacutamab induced depletion of skin KIR3DL2+ CD4+ cells regardless of their density and percentage among CD4+ T cells, which occur prior to the median time to skin response. The patients responding to lacutamab in skin have higher baseline CD68+ CD16+ macrophage density suggesting antibody-dependent cell phagocytosis is a mechanism of action of lacutamab in skin.

These data confirm at a translational level the activity of lacutamab, and its potential as a compelling future treatment option for SS patients with high unmet medical need.

The presentation and poster will be available in the publication section of Innate Pharma’s website.

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 in 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 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 9, 2024 Mendus AB ("Mendus" publ; IMMU.ST), a biopharmaceutical company focused on immunotherapies addressing tumor recurrence, reported that it has presented positive survival data from the ongoing ADVANCE II Phase 2 trial at the ASH (Free ASH Whitepaper) 2024 conference (Press release, mendus, DEC 9, 2024, View Source [SID1234648904]). The data showed that the majority of AML patients treated with vididencel remain alive and disease-free in long-term follow-up, with a median follow-up of 41.8 months.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

AML is an aggressive blood-borne tumor which requires immediate chemotherapy to reduce the level of malignant blasts in bone marrow and blood. After chemotherapy, the risk of disease relapse due to residual cancer cells is high and the only potentially curative approach in AML is a hematopoietic stem cell transplant (HSCT, or "bone marrow transplant"). Mendus’ lead product vididencel is designed to stimulate active immunity against residual cancer cells. Active immunity, built up by the patient’s immune system, is the only long-lasting form of immunity. Mendus is developing vididencel as a maintenance therapy in AML, in order to improve disease-free and overall survival in patients who are in first complete remission following first-line chemotherapy.

"We are encouraged by the updated survival data presented at ASH (Free ASH Whitepaper) confirming that the majority of patients treated with vididencel as part of the ADVANCE II trial are alive today at a median follow-up of 41.8 months, with all patients having passed 3-year follow-up and two patients already 5-year follow-up." said Erik Manting, CEO of Mendus. "These data mark a significant milestone for Mendus, and support our accelerated preparations for a registration trial, bringing vidicencel to the final development stage before it can broadly reach patients in need. In parallel, we will look for opportunities to initiate additional trials, such as the ongoing AMLM22-CADENCE trial evaluating vididencel with oral azacitidine, in collaboration with the Australasian Leukaemia and Lymphoma Group. The preclinical data presented at ASH (Free ASH Whitepaper) further support the broader exploration of vididencel as a maintenance therapy in AML and potentially other blood-borne tumors, such as CML."

ADVANCE II data presented at ASH (Free ASH Whitepaper)
The ADVANCE II Phase 2 trial is an international multi-center Phase 2 trial evaluating vididencel as maintenance treatment for AML patients in first complete remission (CR1) following chemotherapy. Patients participating in the trial were ineligible for HSCT and had measurable residual disease (MRD), which is associated with increased relapse rates. The ADVANCE II trial has completed the active study phase of 70-week follow-up from the start of vididencel treatment and patients are now in long-term follow up.

The updated ADVANCE II data presented at ASH (Free ASH Whitepaper) show that 13 out of 20 patients treated with vididencel were alive and 11 patients were still in CR1 as of the November 4, 2024 cut-off-date, with a median follow-up of 41.8 months. Median relapse-free (RFS) and overall survival (OS) was not reached, as the majority of patients remained alive and disease-free. All patients had passed 3-year follow-up and 2 patients completed 5-year follow-up. The 1-year survival stood at 88%, 3-year survival at 71% and the estimated 5-year survival was 58%.

The only drug approved for post-chemo AML maintenance therapy is oral azacitidine, which in MRD-positive patients led to a median RFS of 7.1 months and a median OS of 14.6 months in the registration trial1. The estimated 3-year OS for the whole treated patient population which included MRD-positive and -negative patients was 37.4% and 5-year OS was 26.5%2.

(1Roboz et al. (2022) Blood; 139(4):2145, 2Wei et al., (2023) Am J Hematol 98: E84)

Immunomonitoring data from the ADVANCE II trial presented at ASH (Free ASH Whitepaper) demonstrated that patients with multiple T cell responses following vididencel treatment (sustained vaccine-induced responses, or sVIR) had a significantly better OS than patients without a sVIR (p=0.036) and a higher number of MRD responses, with 6 our of 9 patients showing MRD clearance or > 10-fold reduction in MRD level. There were also clear differences between patient groups at baseline. Particularly patients with high levels of B cells and low levels of inhibitory T cells showed significantly improved OS (p=0.0109) and the majority of these patients (6 out of 8) demonstrated sVIR following vididencel treatment. The data confirm that vididencel stimulates a broad, active immune response against residual disease, which is associated with improved clinical outcome.

"The data presented at ASH (Free ASH Whitepaper) confirm that vididencel acts as an active immunotherapy against residual cancer cells and has the potential to deliver durable clinical responses in AML. Combined with a strong safety profile, we believe this makes vididencel one of the most promising maintenance treatments currently in development in AML." said Jeroen Rovers, CMO of Mendus. "Based on the positive ADVANCE II data, we are executing on a clinical trial strategy aimed at market registration of vididencel in AML, while exploring opportunities to broaden the addressable patient population."

Other abstracts presented at ASH (Free ASH Whitepaper)
In addition to the ADVANCE II Phase 2 trial data in the post-chemotherapy maintenance setting, Mendus presented two abstracts based on preclinical data exploring the use of vididencel in additional patient populations. AML patients ineligible for high-intensity chemotherapy can be treated today with a combination of azacitidine (AZA) and venetoclax (VEN). In vitro data demonstrated that AZA and VEN do not interfere with vididencel’s mode of action and that VEN stimulates the processing of vididencel by antigen-presenting cells. In vivo data confirmed that vididencel and AZA+VEN act synergistically in a humanized mouse model for AML, supporting the clinical exploration of vididencel in AML patients treated with AZA+VEN. The second preclinical abstract addressed the potential use of vididencel in chronic myeloid leukemia (CML). Data showed that vididencel can stimulate cellular immunity against a CML cell line and investigated the combination potential of vididencel with different tyrosine kinase inhibitor drugs currently used for the treatment of CML. The possibility to improve immunity against residual cancer cells with vididencel addresses the need to improve treatment-free remission rates, allowing CML patients to control their disease without the need for life-long medication.
All data presented at ASH (Free ASH Whitepaper) are available on the Mendus corporate website via View Source

On December 9, 2024 Ichnos Glenmark Innovation (IGI), a global fully integrated clinical-stage biotech company developing multispecifics in oncology, reported first-time clinical data from the early dose-escalation portion of its Phase 1 study of ISB 2001 for the treatment of relapsed or refractory multiple myeloma (RRMM) (Press release, Ichnos Sciences, DEC 9, 2024, View Source;utm_medium=rss&utm_campaign=igi-presents_first-clinical_data_from-phase-1-study_of_trispecific_treat_antibody_isb-2001_showing_high_overall-response_rate_orr_with_durable_responses_and_favorable_safety_profile_in_pa [SID1234648903]). ISB 2001 is an investigational trispecific TREAT antibody for the treatment of RRMM that targets BCMA and CD38 on myeloma cells and CD3 on T cells. Initial results from 20 patients treated as of October 1, 2024, demonstrated an overall response rate (ORR) of 75% (15/20) across all doses tested (0.005 to 1.2 mg/kg), with a stringent complete remission (sCR) and complete remission (CR) rate of 20%. The ORR was 83% among the 18 patients treated at active doses (0.05 mg/kg and higher doses), including sCR/CR rate of 22%. The safety profile was mild with good tolerability, comparing favorably with first-generation 1+1 bispecifics.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The data were presented today during an oral session at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, CA.

"The data presented today on ISB 2001 highlight its remarkable effectiveness as a novel trispecific-antibody T cell engager," said Professor Hang Quach, M.D., Professor of Haematology at the University of Melbourne and Director of Haematology at St Vincent’s Hospital Melbourne. "These results are among the most impressive I have seen in this patient population. ISB 2001 has the potential to revolutionize the treatment landscape for heavily pretreated patients with multiple myeloma who have exhausted currently approved therapies."

ISB 2001 was designed to enhance avidity with two binders targeting distinct myeloma-associated antigens – even at low expression levels – while offering improved safety compared to first-generation bispecific antibodies. IGI is developing ISB 2001 to meet the critical needs of RRMM patients, who have received prior T-cell directed therapies (including CAR-T cells and bispecifics).

"Early data based on only 20 patients are encouraging. ISB 2001 showed high clinical responses in a heavily pretreated and advanced patient population. Combined with a favorable safety and tolerability profile, these findings suggest ISB 2001 could represent a major advance in the treatment of RRMM in the future," said Lida Pacaud, M.D., Chief Medical Officer at IGI. "We are excited to advance the development of ISB 2001 by completing dose-escalation and moving swiftly into the dose-expansion part of the trial to establish the recommended Phase 2 dose and optimal dosing schedule."

ISB 2001 Phase 1 Dose Escalation Study Design

The Phase 1, first-in-human, open-label study is evaluating the safety and anti-myeloma activity of ISB 2001 in patients with RRMM (NCT05862012). The study is enrolling patients with RRMM who have been treated with immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies and are refractory to, or intolerant of, established therapies known to provide clinical benefit in multiple myeloma. Patients with prior CAR-T cell therapies, bispecifics and/or prior BCMA targeted agents were eligible.

The study is being conducted in two parts: dose escalation and dose expansion. This dataset comes from patients treated in the dose escalation at six sites in the United States and Australia.

Preliminary ISB 2001 Phase 1 Dose Escalation Results

The early portion of the trial is evaluating the safety and anti-myeloma activity of ISB 2001. Twenty heavily pretreated patients with RRMM were enrolled as of October 1, 2024. These patients had received a median of 6 prior lines of therapy. Six patients (30%) had extra-medullary plasmacytomas, and 4 of the 12 patients assessed (33%) had high cytogenetic risk. Five (25%) patients were triple-refractory, 14 (70%) were penta-exposed, 2 (10%) were penta-refractory and 13 (65%) were refractory to the last therapy prior to study entry. About half of patients (n=9) had received bispecific antibodies, with other prior therapies including anti-BCMA targeted therapies (n=8), and CAR-T cell therapies (n=2).

ISB 2001 showed a favorable safety profile in patients with heavily pretreated RRMM. No dose-limiting toxicity was detected, and no adverse events led to treatment discontinuation. Grade 1 CRS was observed in 13 patients (65%), and only 2 patients (10%) experienced Grade 2. The median duration of CRS was 2 days (range: 1–8). No immune cell-associated neurotoxicity syndrome (ICANS) was observed. Injection site reactions were reported in 10 patients (50%), all Grade 1. Grade 3 infections were reported in 3 patients (15%).

In the 20 heavily pretreated patients, the ORR was 75% across all dose levels.

Responses to ISB 2001 at active doses (0.05 mg/kg or higher) were durable and deepened over time:

The ORR was 83% among the 18 patients which included stringent Complete Responses (sCRs) in 3 patients (17%), Complete Response in 1 patient (6%), Very Good Partial Responses (VGPRs) in 9 patients (50%), and Partial Responses (PRs) in 2 patients (11%).
The median time to first objective response was 36 days (range: 29–99).
16 patients (80%) remain on treatment at data cutoff.
Dose-proportional PK with long half-life of over 10 days and low immunogenicity (2/20 patients, 10% across all doses tested) support exploring less-frequent dosing than weekly subcutaneous administration.

T cell activation, proliferation and soluble BCMA reduction were observed in most patients at effective doses.

Potential Opportunity for ISB 2001

ISB 2001 was developed using IGI’s proprietary BEAT protein platform, which combines TCR interface-based heavy chain pairing and universal light chain technology to create multispecific antibodies. This innovative design can increase binding to tumor cells while minimizing on-target, off-tumor side effects and/or boost immune cell activity against tumor cells by triggering multiple signals.

"While there have been significant advancements in treatments for relapsed/refractory multiple myeloma, many patients still experience relapse. IGI designed ISB 2001 to offer a therapeutic option to patients who have previously received T-cell directed therapies including first-gen bispecific and CAR-T cell therapies." said Cyril Konto, M.D., President and CEO of IGI. "These results further validate IGI’s BEAT technology which addresses the stability and engineering bottlenecks that previously hindered the large-scale production of bispecific and multispecific antibodies."