On December 09, 2024 GSK plc (LSE/NYSE: GSK) reported statistically significant and clinically meaningful overall survival (OS) results from a planned interim analysis of the DREAMM-7 trial evaluating belantamab mafodotin in combination with bortezomib plus dexamethasone (BVd) versus daratumumab in combination with bortezomib plus dexamethasone (DVd) as a second line or later treatment for relapsed or refractory multiple myeloma (Press release, GlaxoSmithKline, DEC 9, 2024, View Source [SID1234648954]). These data were featured today in an oral presentation at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

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The OS findings from DREAMM-7 build on previous data from the DREAMM-71 and DREAMM-82 trials, which showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for both belantamab mafodotin-based combinations versus standard of care comparators.

Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: "The compelling overall survival data from the DREAMM-7 trial establish the potential of belantamab mafodotin in combination to significantly extend the lives of patients with multiple myeloma at or after first relapse. This represents an important advancement that could redefine the treatment of relapsed or refractory multiple myeloma."

With a median follow up of 39.4 months, the analysis presented today shows a statistically significant 42% reduction in the risk of death among patients receiving the belantamab mafodotin combination (n=243) versus the daratumumab-based comparator (n=251) (HR 0.58; 95% CI: 0.43-0.79; p=0.00023). Although the median overall survival (mOS) was not reached in either arm of the study, the projected mOS for BVd is 84 months compared to 51 months for DVd.3

The three-year OS rate was 74% in the belantamab mafodotin combination arm and 60% in the daratumumab combination arm. The survival benefit favoring BVd was seen as early as four months and was sustained over time as illustrated by the separation of the lines in the Kaplan-Meier curve shown above.

María-Victoria Mateos, MD, PhD, Head of Myeloma and Clinical Trials Unit, Hematology Department and Professor of Medicine at the University of Salamanca, Spain, and DREAMM-7 principal investigator, said: "The totality of evidence from DREAMM-7 represents a potential paradigm shift for multiple myeloma patients who have experienced a relapse or become refractory to initial treatment. The OS results shown with the belantamab mafodotin combination in DREAMM-7 further cement the potential of this regimen to prolong the lives of patients with relapsed or refractory multiple myeloma compared to a standard of care daratumumab combination."

The belantamab mafodotin combination also showed statistically significant superiority on the key secondary endpoint of minimal residual disease (MRD) negativity (no detectable cancer cells) compared to the daratumumab combination. The greater than 2.5-fold improvement in the rate of MRD negativity seen at the time of the primary analysis for patients who received BVd can now be declared as statistically significant (p<0.00001) after the positive OS readout based on the predefined testing procedure. This further underscores the transformative potential of this belantamab mafodotin combination for multiple myeloma patients at or after their first relapse.

In addition to OS and MRD negativity, the belantamab mafodotin combination resulted in clinically meaningful improvements in all key secondary efficacy endpoints compared to the daratumumab combination, including duration of response (DOR) and progression-free survival 2 (PFS 2). The results indicate deeper and more durable responses among patients treated with BVd compared to DVd.

The safety and tolerability of the belantamab mafodotin regimen were consistent with the primary analysis and known safety profile of the individual agents. Grade 3 or higher adverse events of clinical interest in the belantamab mafodotin combination and daratumumab combination arms, respectively included thrombocytopenia (56% versus 35%; 34 versus 25 patients/100 person-years); anemia (9% versus 10%; exposure-adjusted rate [per 100 person-years] not reported); and neutropenia (14% versus 10%; 8 versus 7 patients/100 person-years).

Eye-related side effects, a known risk of treatment with belantamab mafodotin, were generally manageable and resolvable with dose modification, and led to a low (10%) treatment discontinuation rate.

Full data summaries for OS and other key secondary endpoints are shown below.

Key Secondary Endpoints
Endpoint

belantamab mafodotin +
bortezomib + dexamethasone (BVd)
n=243

daratumumab +
bortezomib + dexamethasone (DVd)
n=251

OS (overall survival), HR (95% CI)

0.58 (0.43-0.79)

P-value1

p=0.00023

OS, median (95% CI), months

NR (NR-NR)

NR (41.0-NR)

OS rate at 24 months, % (95% CI)

79% (73-84)

67% (61-73)

OS rate at 36 months, % (95% CI)

74% (68-79)

60% (54-66)

MRD (minimal residual disease) negativity rate for patients with CR or better, % (95% CI)

25.1% ​(19.8-31.0)​

10.4% ​(6.9-14.8)​

ORR (overall response rate), % (95% CI)

83.1% ​(77.8-87.6)

71.3% ​(65.3-76.8)​

CR (complete response), or better, % (95% CI)

35.8% ​(29.8-42.2)

17.5% ​(13.0-22.8)​

VGPR (very good partial response), or better, % (95% CI)

66.3%​ (59.9-72.2)

46.2% ​(39.9-52.6)​

Median DOR (duration of response) (95% CI), months

40.8 (30.5-NR)​

17.8 (13.8-23.6)​

Median PFS 2 (progression-free survival 2), months

NR (45.6-NR)​

33.4 (26.7-44.9)

HR

0.59 (0.45-0.77)

1One-sided p-value based on stratified log-rank test.

In 2024, regulatory filings for belantamab mafodotin combinations for the treatment of relapsed or refractory multiple myeloma based on the results of the DREAMM-7 and DREAMM-8 trials have been accepted in the US4, European Union5, Japan6 (with priority review), China (for DREAMM-7 only, with priority review; Breakthrough Therapy Designation7 also granted), United Kingdom, Canada and Switzerland (with priority review for DREAMM-8).

About the DREAMM clinical development program

The DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical development program continues to evaluate the potential of belantamab mafodotin in early lines of treatment and in combination with novel therapies and standard of care treatments. In addition to DREAMM-7 and DREAMM-8, a phase III study in newly diagnosed transplant ineligible multiple myeloma, DREAMM-10, is expected to be initiated by the end of 2024.

About DREAMM-7

The DREAMM-7 phase III clinical trial is a multi-center, open-label, randomized trial evaluating the efficacy and safety of belantamab mafodotin in combination with bortezomib plus dexamethasone (BVd) compared to a combination of daratumumab and bortezomib plus dexamethasone (DVd) in patients with relapsed/refractory multiple myeloma who previously were treated with at least one prior line of multiple myeloma therapy, with documented disease progression during or after their most recent therapy.

A total of 494 participants were randomized at a 1:1 ratio to receive either BVd or DVd. Belantamab mafodotin was scheduled to be dosed at 2.5mg/kg intravenously every three weeks.

The primary endpoint is PFS as per an independent review committee. The key secondary endpoints include OS, duration of response (DOR), and minimal residual disease (MRD) negativity rate as assessed by next-generation sequencing. Other secondary endpoints include overall response rate (ORR), safety, and patient reported and quality of life outcomes.

Results from DREAMM-7 were first presented1 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series in February 2024, shared in an encore presentation at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting, and published in the New England Journal of Medicine.

About multiple myeloma

Multiple myeloma is the third most common blood cancer globally and is generally considered treatable but not curable.8,9 There are approximately more than 180,000 new cases of multiple myeloma diagnosed globally each year.10 Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.11 Many patients with multiple myeloma, including approximately 65% in the US, are treated in a community cancer setting, leaving an urgent need for new, effective therapies with manageable side effects that can be administered outside of an academic center.12,13,14

About belantamab mafodotin

Belantamab mafodotin is an investigational antibody-drug conjugate comprising a humanized B-cell maturation antigen monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker. The drug linker technology is licensed from Seagen Inc.; the monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa Inc., a member of the Kyowa Kirin Group.

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]).

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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 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported new and updated data for odronextamab were presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, CA (Press release, Regeneron, DEC 9, 2024, View Source [SID1234648923]). The presentations, including two orals, showcase the depth and breadth of the odronextamab clinical development program, with twelve abstracts spanning several B-cell non-Hodgkin lymphoma (B-NHL) subtypes across earlier lines of treatment.

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OLYMPIA-1 Part 1 Results Showcased Compelling Potential in Previously Untreated Follicular Lymphoma (FL)
The ongoing Phase 3 OLYMPIA-1 confirmatory trial consists of a non-randomized safety run-in (Part 1) followed by a randomized efficacy portion (Part 2) evaluating odronextamab monotherapy versus rituximab plus standard-of-care chemotherapies.

In Part 1 (N=13), odronextamab led to complete responses (CR) in all 12 patients evaluable for efficacy at week 12. Historical clinical trial data indicate that the standard-of-care regimen R-Chemo was associated with an objective response rate (ORR) of 89% and 67% CR rate.1 Among the 13 patients evaluable for safety, none experienced a dose-limiting toxicity (DLT). The most common treatment-emergent adverse events (TEAEs) were cytokine release syndrome (CRS; 62%), diarrhea (46%) and rash (39%). All cases of CRS were Grade 1. Infections occurred in 39% of patients, and 15% experienced a Grade 3 infection. Grade ≥3 TEAEs occurred in 46% of patients, which included one patient who discontinued early due to elevated liver enzymes. There were no reports of tumor lysis syndrome (TLS) or immune effector cell associated neurotoxicity syndrome (ICANS).

"The OLYMPIA-1 Phase 3 trial is designed to explore a novel, chemotherapy-free, fixed duration treatment that is being studied in the outpatient setting in patients with previously untreated follicular lymphoma," said Elizabeth Brém, Associate Clinical Professor, Division of Hematology/Oncology at UC Irvine. "These compelling, initial data show the paradigm-changing potential of odronextamab in previously untreated patients and reinforce the remarkable complete response rates odronextamab demonstrated in late-line follicular lymphoma. We look forward to seeing the results of the Part 2 portion, which offers the first head-to-head evaluation of odronextamab monotherapy compared to standard-of-care chemo-immunotherapies."

Durable Responses Shown in Diffuse Large B-Cell Lymphoma (DLBCL) that has Progressed After CAR-T Therapy
The primary analysis from an expansion cohort of the ELM-1 trial, which evaluated patients with DLBCL who progressed after CAR-T therapy, were presented in an oral session. Among 60 patients – with a median duration of treatment of 12 weeks (range <1 to 154 weeks) and a median duration of follow-up of 16 months – results assessed by independent central review showed:

48% ORR, with 32% achieving a CR. These responses were observed across patients with high-risk features, including those that were refractory to their last therapy, double refractory, or refractory prior to CAR-T.
Among all patients, there was a 15-month median duration of response (DoR) (95% confidence interval [CI]: 3 months to not estimable [NE]), 5-month median progression-free survival (PFS) (95% CI: 3 to 5 months), and a 10-month median overall survival (OS) (95% CI: 5 to 16 months).
Among CR patients, medians were not reached in terms of PFS (95% CI: 9 months to NE) and OS (95% CI: 15 months to NE).
All patients experienced TEAEs, including 77% who experienced Grade ≥3 TEAEs. CRS occurred in 48% of patients (25% were Grade 1 and 23% were Grade 2). Infections occurred in 50% of patients, and 20% experienced a Grade ≥3 infection, including one treatment-related death due to COVID-19 pneumonia. No TLS or ICANS cases were reported.

"Studies show that half of patients receiving CAR-T therapies relapse within six months, and up to 35% of patients do not go on to receive subsequent treatments, highlighting the critical unmet need in diffuse large B-cell lymphoma progressing after CAR-T," said Matthew Matasar, M.D., MS, Chief of Blood Disorders at Rutgers Cancer Institute and RWJBarnabas Health. "ELM-1 is one of the only trials that has prospectively evaluated the efficacy and safety of a CD20xCD3 bispecific antibody in patients with relapsed or refractory large B-cell lymphoma progressing after CAR-T therapy. It is encouraging to see these outcomes with odronextamab in a patient population that to date has had an incredibly poor prognosis and limited treatment options."

Compelling Efficacy Highlighted in Marginal Zone Lymphoma (MZL) in Heavily Pretreated Patients
Another oral presentation featured data from a cohort of heavily pretreated patients with relapsed/refractory (R/R) MZL, a setting with no approved treatment options. In the potentially pivotal ELM-2 trial, 42 patients were enrolled, of which 35 patients were evaluable for efficacy. At a median duration of follow-up of 11 months, results showed:

77% ORR, with all responders achieving a CR, per investigator assessment.
Medians were not reached in terms of DoR (95% CI: 12 months to NE), duration of CR (95% CI: 12 months to NE), PFS (95% CI: 15 months to NE) and OS (95% CI: NE to NE).
Among 42 patients evaluated for safety, the most common TEAEs (≥15%) were CRS (55%; all were Grade 1 or 2), infusion-related reaction (36%), pyrexia (36%) and neutropenia (31%). Grade ≥3 TEAEs occurred in 83% of patients and included neutropenia and increased levels of alanine aminotransferase and aspartate aminotransferase. Infections occurred in 69% of patients, and 24% experienced a Grade ≥3 infection. Four patients (10%) discontinued treatment due to TEAEs.

Odronextamab is approved in the European Union as Ordspono to treat R/R FL or DLBCL after two or more lines of systemic therapy but its safety and efficacy have not been fully evaluated by any other regulatory authority. For complete product information, please see the Summary of Product Characteristics that can be found on www.ema.europa.eu. The U.S. regulatory resubmission for odronextamab in R/R FL after two or more lines of systemic therapy is expected to be submitted in the first half of 2025. The potential use of odronextamab in R/R MZL is investigational and has not been approved by any regulatory authority.

About B-Cell Non-Hodgkin Lymphomas (B-NHL)
B-NHL is the most common lymphoma in the United States and has several different subtypes including FL, DLBCL and MZL. FL and MZL are slow-growing subtypes, and both are incurable. It is estimated that approximately 120,000 FL cases are diagnosed annually worldwide, while MZL is estimated to be 5 to 10% of NHLs. DLBCL is an aggressive subtype, with up to 50% of high-risk patients experiencing progression after first-line treatment. It is estimated that approximately 163,000 DLBCL cases are diagnosed annually worldwide.

About the Odronextamab Clinical Trial Program
Odronextamab is a CD20xCD3 bispecific antibody designed to bridge CD20 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation and cancer-cell killing. It is being investigated in a broad clinical program spanning several trials.

ELM-1 is an ongoing, open-label, multicenter Phase 1 trial to investigate the safety and tolerability of odronextamab in patients with CD20+ B-cell malignancies previously treated with CD20-directed antibody therapy, including a cohort of patients who had progressed after CAR-T therapy.

ELM-2 is an ongoing, open-label, multicenter Phase 2 trial investigating odronextamab across five independent disease-specific cohorts, including DLBCL, FL, mantle cell lymphoma, MZL and other subtypes of B-NHL. The primary endpoint is ORR according to the Lugano Classification as assessed by IRC, and secondary endpoints include CR, PFS, OS and DoR.

OLYMPIA is a broad Phase 3 clinical trial program investigating odronextamab in earlier lines of therapy and other B-NHLs and includes:

OLYMPIA-1 evaluating odronextamab against rituximab plus standard-of-care chemotherapies in FL.
OLYMPIA-2 evaluating odronextamab plus chemotherapy against rituximab plus standard-of-care chemotherapies in FL.
OLYMPIA-3 evaluating odronextamab plus chemotherapy against rituximab plus standard-of-care chemotherapies in previously untreated DLBCL.
OLYMPIA-4 evaluating odronextamab compared to an investigator’s choice of standard-of-care regimens in previously treated aggressive B-NHL.
OLYMPIA-5 evaluating odronextamab plus lenalidomide against rituximab plus lenalidomide in FL and MZL.
Regeneron is also investigating additional odronextamab combination therapies in R/R aggressive B-NHL. These include the ATHENA-1 trial evaluating odronextamab in combination with a costimulatory CD22xCD28 bispecific antibody (REGN5837) and the CLIO-1 trial evaluating odronextamab in combination with Regeneron’s PD-1 inhibitor Libtayo (cemiplimab).

These potential uses described in the OLYMPIA, ATHENA-1 and CLIO-1 trials are investigational, and their safety and efficacy have not been evaluated by any regulatory authority. For more information, visit the Regeneron clinical trials website or contact via [email protected] or +1 844-734-6643.

On December 9, 2024 Carisma Therapeutics Inc. (Nasdaq: CARM) ("Carisma" or the "Company"), a leader in macrophage-focused therapeutics, reported a strategic reprioritization of its pipeline, cessation of development of CT-0525, and a reduction in the workforce by 34% (Press release, Carisma Therapeutics, DEC 9, 2024, View Source [SID1234648939]). These measures will enable Carisma to focus its resources on advancing its in vivo macrophage engineering platform for the development of fibrosis, oncology and autoimmune disease therapies. This decision aligns Carisma’s efforts with next-generation, high-potential programs addressing significant unmet patient needs while enhancing operational efficiency.

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"Following a comprehensive review of our portfolio, we have made the strategic decision to prioritize advancing our in vivo macrophage engineering platform," said Steven Kelly, President and Chief Executive Officer of Carisma. "The compelling data generated by both the Moderna-partnered in vivo CAR-M oncology programs as well as our internal liver fibrosis program underscore the potential to revolutionize treatment paradigms with an innovative and patient-centric approach."

"These strategic initiatives, re-directing our investments to the in vivo macrophage engineering platform, discontinuing development of our anti-HER2 program and reducing our workforce, aim to streamline our operations and reduce operating expenses over time," Kelly continued. "While these decisions are very challenging, they are made in the best interest of our shareholders. We remain deeply grateful for the significant contributions of the employees departing Carisma."

Reprioritization Plan, Pipeline Updates, and Upcoming Milestones:

As part of this reprioritization of our pipeline, Carisma will discontinue development of the anti-human epidermal growth factor receptor 2 ("anti-HER2") program, and redirect the Company’s focus to developing off-the-shelf products using its in vivo macrophage engineering platform:

Fibrosis

Carisma’s initial fibrosis program is focused on addressing liver fibrosis, a significant global health challenge. Preclinical data presented at the American Association for the Study of Liver Diseases (AASLD) Liver Meeting 2024 demonstrated the potential of Carisma’s engineered macrophages to reduce inflammation, resolve fibrosis, and promote liver regeneration.
The Company plans to nominate a development candidate for its liver fibrosis program in the first quarter of 2025, reflecting its expertise in macrophage biology and fibrotic diseases.
Oncology

In collaboration with Moderna, Inc. (Nasdaq: MRNA), Carisma is advancing multiple programs utilizing an in vivo chimeric antigen receptor macrophage and monocyte ("CAR-M") plus mRNA/LNP approach. The lead program is an anti-glypican 3 (GPC3) in vivo CAR-M therapy that has demonstrated the potential for this scalable, patient-friendly approach to transform solid tumor therapy. In addition to this program, Moderna has nominated four undisclosed oncology research targets under the collaboration and has the right to designate up to ten oncology targets as development targets.
Autoimmune

In collaboration with Moderna, Carisma has two in vivo CAR-M research programs for the treatment of autoimmune diseases associated with two distinct targets where there is significant unmet medical need.
Carisma retains all rights in autoimmune disease beyond these two nominated targets.
Discontinuation of anti-HER2 Development

The Company’s decision was based on an assessment of the competitive landscape in anti-HER2 treatments, including the impact of recently approved anti-HER2 therapies on HER2 antigen loss/downregulation, and the effects on the future development strategy of any anti-HER2 treatment.
The Company has completed patient enrollment of the Phase 1 clinical trial of CT-0525 and will not enroll patients in the previously planned Cohort 3 of the study.
Based on the data available to date from the anti-HER2 program, CAR-M cell therapy has been shown to be safe, well-tolerated, and feasible to manufacture, and it holds the potential to become a meaningful treatment option for patients.
Corporate Updates

As part of the strategic restructuring, Carisma will reduce its workforce by 34%. The Company expects the reduction in workforce to be substantially complete and to pay the majority of related reduction in workforce amounts by the end of the first quarter of 2025. The Company is committed to supporting affected employees through this transition.
As part of the workforce reductions, our Chief Financial Officer, Richard Morris, our General Counsel, Eric Siegel, and our Senior Vice President, Human Resources, Terry Shields, will leave the Company effective December 31, 2024. Carisma expresses gratitude for their contributions.
The Company expects to incur approximately $2.7 million in connection with the reduction in the workforce, which primarily represents one-time employee termination benefits directly associated with the workforce reduction.

On December 09, 2024 Opna Bio, a clinical-stage biopharmaceutical company focused on the discovery and development of novel oncology therapeutics, reported interim data from its lead clinical program, OPN-2853, in patients with advanced myelofibrosis showing encouraging levels of spleen reduction, with minimal toxicities and adverse events (Press release, Opna Bio, DEC 9, 2024, View Source [SID1234648955]). Preclinical data from a second program, OPN-6602, showed significant tumor regression in multiple myeloma models as a single agent and in combination with other therapeutics. The presentations took place this weekend at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting, December 7-10, 2024, in San Diego.

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OPN-2853 Shows Spleen Reduction in Patients with Advanced Myelofibrosis

OPN-2853, a small molecule bromodomain and extra-terminal motif (BET) inhibitor, is being evaluated in an ongoing Phase 1 investigator-led study in patients with advanced myelofibrosis who are no longer responding to ruxolitinib alone. Myelofibrosis is a type of blood cancer that causes fibrosis in the bone marrow, anemia and enlarged spleen, amongst other symptoms. The study is testing three dose levels of OPN-2853 (20 mg, 40 mg and 80 mg), given orally once daily, in combination with ruxolitinib. As of February 2024, the cut-off date, 16 patients had been enrolled at different dose levels, across multiple sites in the United Kingdom, coordinated by the Cancer Research UK (CRUK) Clinical Trials Unit at the University of Birmingham.

In 12 evaluable patients, the median spleen size was reduced from baseline with spleens no longer palpable in 50% of evaluable patients. The combination dose has been well tolerated, and the majority of patients have completed eight cycles of combination treatment.

"We are very encouraged by these data to date, which demonstrate that daily dosing of OPN-2853 in combination with ruxolitinib was well tolerated, and showed spleen reduction in patients with myelofibrosis who have very limited options once they have progressed," said principal investigator Adam Mead, PhD, MRCP, FRCP, professor of hematology at the University of Oxford and CRUK senior cancer research fellow. "We are enthusiastic about the OPN-2853 and ruxolitinib combination and expect to have a recommended Phase 2 dose in early 2025."

Opna Bio is planning further clinical development with OPN-2853.

OPN-6602 Combinations Demonstrate Complete Tumor Regression in Preclinical Multiple Myeloma Models

OPN-6602, an oral, small molecule inhibitor of the E1A binding protein (EP300) and CREB-binding protein (CBP), is currently being tested in a Phase 1 trial in patients with multiple myeloma (MM). MM is a type of blood cancer derived from malignant plasma cells in the bone marrow.

In MM mouse xenograft models, OPN-6602 showed 71% tumor suppression as a single agent, and 100% tumor regression when combined with dexamethasone, pomalidomide or mezigdomide with a sustained duration of response. RNA sequencing of treated tumors showed that OPN-6602 downregulated key MM driver and signature genes, and has the potential to overcome resistance mechanisms to standard-of-care regimens.

"We are very encouraged by the strength of the OPN-2853 clinical and OPN-6602 preclinical data, which highlights the potential of their unique pharmacokinetic profiles and validates our ‘safety by design’ approach. Both drug candidates have a high Cmax and short half-life, which allows for continuous daily dosing and effective target engagement with rapid clearance to mitigate toxicities," said Gideon Bollag, PhD, co-founder and chief scientific officer of Opna Bio. "This confers a significant advantage to these drugs when used as single agents and a potentially synergistic effect when used in combination with other therapies."