On December 9, 2024 Cimeio Therapeutics reported that it has entered a research collaboration with Kyowa Kirin Co., Ltd. (Kyowa Kirin) to develop a novel therapy for diseases with high unmet need (Press release, Cimeio Therapeutics, DEC 10, 2024, View Source [SID1234648894]).

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The partnership combines Cimeio’s proprietary Shielded Cell and Immunotherapy (SCIP) platform with Kyowa Kirin’s expertise in cellular therapies and underscores both companies’ commitment to using emerging cell and gene therapy technologies to develop new ways to treat patients. Under the terms of the agreement, Cimeio is eligible to receive an upfront payment and two years of research funding. Upon Kyowa Kirin’s exercise of a commercial license option, Cimeio will be eligible for development and commercial milestones as well as royalties on sales of potential products arising from the partnership. Further terms are not disclosed.

Cimeio’s SCIP platform is based on the development of novel immunotherapies enabled by epitope-shielded cells. These cells contain modified variants of naturally occurring cell surface proteins that maintain their function but are resistant to depletion by the paired immunotherapy. These shielded cells enable the development of powerful therapeutics for previously undruggable targets, targeted conditioning for HSC transplant, and immune system reset amongst other applications.

"We are thrilled to collaborate with Kyowa Kirin, a company with a rich history of investing in innovative technologies that have the potential to significantly improve outcomes for patients with serious conditions," said Dr. Stefanie Urlinger CSO of Cimeio. "This partnership represents a significant step forward for our company and mission."

"Kyowa Kirin and Cimeio share the vision for the potential of therapeutics enabled by epitope-shielded cells," said Yoshifumi Torii, Ph.D, Executive Officer, Senior Vice President, Head of Research Division of Kyowa Kirin. "With this partnership we believe we can develop a safe and effective therapy for diseases that in the past have been incredibly difficult to treat, and we’re looking forward to working with the talented team at Cimeio."

On December 10, 2024 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that new and updated data from its industry-leading CD20xCD3 T-cell-engaging bispecific antibody programme were presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, 7-10 December 2024 (Press release, Hoffmann-La Roche, DEC 10, 2024, View Source [SID1234648977]). With more than 20 bispecific antibody abstracts accepted for presentation, data showcase the benefits of fixed-duration Columvi (glofitamab) and Lunsumio (mosunetuzumab) across different types of aggressive and indolent lymphomas. This research supports Roche’s efforts to continue innovating for patients by advancing treatment standards at earlier stages of disease while exploring additional forms of administration that could further improve the patient experience.

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"The data being presented at ASH (Free ASH Whitepaper) offer further evidence that Columvi and Lunsumio can provide lasting remissions for people with advanced lymphoma," said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. "The results underscore our ambition to transform the treatment of B-cell malignancies with a range of innovative therapeutic options."

"Lymphoma patients face challenges that extend well beyond the clinical manifestations of their disease, including the physical and emotional strain of frequent appointments and treatments," said Elizabeth Budde, M.D., Ph.D., City of Hope’s executive medical director of its Enterprise Immune Effector Cell Program and associate professor in its Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation. "While Lunsumio’s fixed duration intravenous formulation has already offered a valuable treatment option, the introduction of a subcutaneous route could provide a shorter administration time. With both routes available, we can better tailor therapy to each patient’s needs, supporting a flexible and patient-centered approach to follicular lymphoma care."

Follow-up data reinforce benefits of fixed-duration therapies beyond the end of treatment
Three-year follow-up from the pivotal phase II NP30179 study of Columvi in people with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) showed 40.0% of patients achieved a complete response (CR), with a median duration of CR of 29.8 months (95% CI: 22.0–not estimable [NE]). The majority of patients in complete remission at the end of therapy remained in remission two years after therapy completion. Safety appeared consistent with the previous analysis.1

Long-term data at four years from the pivotal phase II GO29781 study of Lunsumio in patients with R/R follicular lymphoma (FL) showed long-lasting remissions, with nearly two-thirds (64.0% [95% CI: 50.1-78.0]) of patients with a CR alive and without disease progression at 45 months. The overall response rate (ORR) and CR rates in the overall population were 77.8% and 60.0%, respectively. Consistent results were seen in patients with a history of disease progression within 24 months of frontline treatment (POD24), which is typically harder to treat. No new safety signals were observed since the previous analysis.2

Both studies also showed restoration of B-cell levels, starting from 12-18 months following Columvi treatment and after a median of 19 months following Lunsumio treatment, indicating immune system recovery and supporting the use of a fixed-duration treatment approach.1,2 Recovery of B cells following treatment for lymphoma is important so that patients can maintain immune system function.

A US real-world data study and economic model evaluating R/R non-Hodgkin lymphoma patient treatment-related travel burden across different bispecific antibody therapies highlight the impact of travel distance, time and associated costs, an often-overlooked aspect of the patient experience beyond clinical efficacy and safety. These factors play a crucial role in treatment decision-making, further emphasising the importance of patient-centred treatment options. The study found fixed-duration therapies, such as Columvi and Lunsumio, reduce treatment-related travel burden due to less frequent dosing.3

Studies investigating subcutaneously-administered Lunsumio show positive results
Data from a primary analysis of the phase II GO29781 study of investigational Lunsumio administered subcutaneously in patients with third-line or later FL were presented for the first time. Results show pharmacokinetic non-inferiority compared to intravenous (IV) administration, with fixed-duration Lunsumio achieving high rates of deep and durable remissions, with 76.6% of patients experiencing an ORR and a 61.7% CR rate, as evaluated by the independent review committee. The median progression-free survival was 23.7 months (95% CI: 14.6-NE), while the median overall survival was not reached. The most common all-grade adverse events (AEs) were injection-site reactions (60.6%; all Grade 1-2), fatigue (35.1%), and cytokine release syndrome (CRS; 29.8%). The rate and severity of CRS events were low (Grade 1-2, 27.6%; Grade 3, 2.1%); all occurred during cycle 1 and were resolved.4 Data has been submitted to health authorities with the aim of offering patients and healthcare providers an alternative treatment and more choice when it comes to administration options depending on their needs.

New data from a randomised phase II cohort of the investigational GO40516 study showed improved efficacy and manageable safety with outpatient, subcutaneously administered, fixed-duration Lunsumio in combination with Polivy (polatuzumab vedotin) versus MabThera/Rituxan (rituximab) in combination with Polivy, in people with R/R LBCL. In the Lunsumio-Polivy arm, the ORR was 77.5% (95% CI: 61.6-89.2) versus 50.0% (95% CI: 33.8–66.2) for MabThera/Rituxan-Polivy, and the CR rate was 57.5% (95% CI: 40.9-73.0) versus 35.0% (95% CI: 20.6-51.7). AEs of special interest occurring in ≥30% of patients in the Lunsumio-Polivy arm were injection-site reactions (55.0%) and neutropoenia (40.0%). CRS events occurred in four (10.0%) patients, all of which were Grade 1-2, occurred during cycle 1 and were resolved.5 These data support further exploration of this investigational treatment combination in the ongoing phase III SUNMO study, which could provide an alternative option in second-line DLBCL to meet diverse patient needs.

Additional data support Roche’s goal to elevate treatment standards in earlier stages of LBCL
Updated data from the phase I/Ib investigational NP39488 study showed high and durable response rates in people with R/R LBCL treated with Columvi in combination with Polivy, including those with high-grade disease and prior treatment with CAR T-cell therapy. Of the 128 efficacy-evaluable patients, the best ORR was 80.6%, with a CR rate of 62.0%, and the median duration of CR was 31.8 months (95% CI: 21.9-NE). Among patients previously treated with CAR T-cell therapy (n=28), the ORR was 75.0%, with a CR rate of 50.0%. The safety profile was manageable and consistent with the known profiles of the individual drugs. The most common AE was CRS (44.4%), which was mostly Grade 1-2.6 Results support ongoing development of this investigational combination in the phase III SKYGLO study investigating Columvi with Polivy-MabThera/Rituxan, cyclophosphamide, doxorubicin and prednisone (R-CHP) in previously untreated DLBCL.

About Columvi (glofitamab)
Columvi is a CD20xCD3 T-cell-engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. Columvi was designed with a novel 2:1 structural format. This T-cell-engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T cells, a type of immune cell, and two regions that bind to CD20, a protein on B cells, which can be healthy or malignant. This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell. Roche is investigating Columvi as a monotherapy and in combination with other medicines for the treatment of diffuse large B-cell lymphoma and mantle cell lymphoma.

About Lunsumio (mosunetuzumab)
Lunsumio is a first-in-class CD20xCD3 T-cell-engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. This dual-targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells. A robust clinical development programme for Lunsumio is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with B-cell non-Hodgkin lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, and other blood cancers.

About Polivy (polatuzumab vedotin)
Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed in the majority of B cells, an immune cell impacted in some types of non-Hodgkin lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to cancer cells such as those expressing CD79b and destroys these B cells through the delivery of an anti-cancer agent, which is thought to minimise the effects on normal cells. Polivy is being developed by Roche using Pfizer ADC technology and is currently being investigated for the treatment of several types of NHL.

On December 10, 2024 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported that the pre-specified threshold of 60 events (deaths) has been reached in its ongoing Phase 3 REGAL clinical trial of galinpepimut-S (GPS) in acute myeloid leukemia (AML), triggering the interim analysis to be conducted by the Independent Data Monitoring Committee (IDMC) (Press release, Sellas Life Sciences, DEC 10, 2024, View Source [SID1234648993]).

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The IDMC will conduct a thorough review of the current REGAL data, and the interim analysis will provide an assessment of efficacy, futility as well as safety of GPS.

"This is an exciting and very important milestone in our efforts to bring forward a new potential treatment option for AML patients," said Angelos Stergiou, MD, ScD hc, President and Chief Executive Officer of SELLAS. "Our mission at SELLAS is to develop novel therapies that prolong patients’ lives, and the outcome of the interim analysis will hopefully bring us closer to the potential of adding GPS as a powerful ally in the battle against AML. Today, we are here thanks to the unwavering support of our shareholders, dedication of our clinical investigators and the resilience of our patients and their families. The IDMC will now carefully review and analyze all the data and have scheduled a meeting in January to review results to date. We are extremely grateful to everybody who have contributed to the REGAL study, and we look forward to sharing the IDMC’s feedback and recommendations as soon as they become available."

The Company will host a call today to review the process leading up to the IDMC meeting and the potential outcomes of the REGAL interim analysis.

To access the webinar, please use the following information:

Date: Tuesday, December 10, 2024
Time: 9:00 a.m. Eastern Time
Webcast: SELLAS GPS REGAL

On December 10, 2024 Syntara Limited (ASX:SNT), a clinical-stage drug development company, reported positive interim data from its ongoing Phase 2 clinical trial evaluating SNT-5505 (200 mg BID) in combination with ruxolitinib (RUX) for the treatment of myelofibrosis (MF) (Press release, Syntara, DEC 10, 2024, View Source [SID1234649009]). The interim results2 suggest that SNT-5505 has potential as a breakthrough therapy for MF and are being presented today at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting (ASH) (Free ASH Whitepaper). Further interim data will be released in 1H 2025 and final data in 2H 2025.

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The interim data suggests that SNT-5505 compares favourably thus far to other drugs being trialled for MF demonstrating excellent tolerability and improvements in symptoms and spleen volume that increase over time.

This is in line with the anticipated disease modifying effects of a pan-LOX inhibitor that works to improve the bone marrow microenvironment and inhibits a growth factor receptor (PDGFR-b) that regulates cell expansion and division. This is encouraging, particularly given the trial patient population with a suboptimal response to existing standard of care and a high disease burden. Despite long prior RUX usage, most patients had high symptom scores and enlarged spleens at their entry into the trial.

Highlights2:

At 12 weeks of treatment, 46% of evaluable patients3 achieved a 50% improvement in Total Symptom Score (TSS50) which improved to 80% at 38 weeks of treatment. TSS50 is a standard efficacy endpoint used as the primary endpoint in MF clinical trials.
30% of evaluable patients4 achieved a spleen volume reduction (SVR) of 25% and 20% achieved an SVR of 35%. Both levels are considered clinically meaningful, with SVR35 a typical endpoint used in MF clinical trials.
Patient symptoms and spleen volume continued to improve over the duration of the interim data which is a novel finding that differentiates SNT-5505 from MF drugs on market and in later stages of development. It highlights the potential of SNT-5505 to be used in combination with JAK inhibitors to change the long-term outcomes for MF patients.
SNT-5505 is safe & well tolerated with no treatment related serious adverse events noted at this interim stage – viewed together with the excellent safety profile seen in the earlier monotherapy study⁵ this is emerging as another key differentiator to MF drugs on the market and in development.
After receiving data from a subset of patients reaching 52 weeks of treatment by March 2025, the company intends to discuss with the FDA the trial design for a pivotal Phase 2c/3 study. Concurrently, the company will also engage with potential global and regional partners.
The open-label study, which aims to assess the safety and efficacy of SNT-5505 over 52 weeks, has enrolled 16 patients with intermediate-2 or high-risk MF to date, with data extracted for use at ASH (Free ASH Whitepaper) on 14 November 2024:

13 patients had reached 12-week visit
8 patients had reached 24-week visit
5 patients had reached 38-week visit
Patients enrolled had a median RUX exposure of 3.2 years and a median baseline symptom score of 23, indicative of a high disease burden.

Professor Claire Harrison, Professor of myeloproliferative neoplasms at Guy’s and St Thomas’ NHS Foundation Trust, commented:

"This interim data confirms the excellent safety profile of SNT-5505 and also suggests that the mechanism of SNT-5505 may exert a long-term effect on the disease, with both symptoms and spleen volume continuing to improve as we now see patients on drug for 9 months. This hasn’t been seen before with this class of drug and holds potential for real long-term benefits for MF patients. I look forward to seeing the data mature in the coming months to confirm these important early findings."

Key points from the interim data2:

Safety and tolerability:
SNT-5505, in combination with a stable dose of RUX, was safe and well tolerated. There were no treatment related serious adverse events (SAEs) attributed to SNT-5505.
Substantial symptom relief observed over time:
At Week 12 – 46% (6/13) of evaluable patients3 achieved a ≥50% reduction in Myelofibrosis Symptom Assessment Form Total Symptom Score (TSS50), a benchmark for clinical response recognised by regulatory authorities such as the FDA.
At Week 38 – 80% (4/5) of evaluable patients achieved a TSS50.
Spleen volume reductions in the majority of patients:
82% (9/11) of evaluable patients3 experienced stable or reduced spleen volume with no dosage adjustments in RUX.
30% (3/10) of evaluable patients achieved an SVR25 and 20% (2/10) achieved an SVR35 with indications that patients were improving further at later timepoints.
Notably, spleen reductions over the period of the interim data were achieved in patients despite significant duration (>2 years) prior RUX exposure with many on low daily doses (≤20 mg/day).
80% (4/5) of evaluable patients showed further reductions in spleen volume from Week 24 to Week 38 which is a novel finding that differentiates SNT-5505 from other treatments on market and in development.
Haematological parameters remain stable:
Haemoglobin levels and platelet counts were generally stable across the cohort, with few major haematological toxicities reported.
One (of 2) transfusion dependent patients showed reduced transfusion requirements (approximately 70% reduction from baseline) over the period of the interim data.
Syntara CEO Gary Phillips added:

"A well tolerated drug that produces increasing and durable benefit the longer patients stay on is an exciting prospect and would differentiate SNT-5505 from other MF drugs on the market and in development. The changes in symptom score seen in the interim data at 9 months, albeit from a relatively small cohort of patients, suggests a superiority to other drugs that have been trialled in this patient group and are particularly important given the emphasis that the FDA and other regulatory bodies place on this measure. We will continue to analyse the data coming in, and anticipate requesting feedback from the FDA on the next stage of clinical development in Q2 2025 when we will have a number of patients with 12 months of treatment data."

Of the 16 enrolled patients, 12 patients were continuing to receive treatment as of the ASH (Free ASH Whitepaper) data cut off. Subsequent to the data cut off, a further three patients discontinued after receiving 6 months of therapy. No discontinuations for adverse events were considered related to SNT-5505 treatment. This level of discontinuations in clinical trials is consistent with a patient group with a high disease burden.

The Phase 2 trial has been designed to evaluate SNT-5505 in combination with RUX in patients with intermediate-2 or high-risk MF. Patients must have been on RUX for at least 12 weeks (stable dose for ≥8 weeks) before enrolling and be symptomatic. The study is being conducted across 19 sites in Australia, South Korea, Taiwan, and the USA, and the last patient visit is expected in July 2025.

On December 10, 2024 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported the initiation of the pivotal TACTI-004 Phase III clinical trial for the treatment of first-line metastatic non-small cell lung cancer (1L NSCLC) (Press release, Immutep, DEC 10, 2024, View Source [SID1234649046]).

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"The receipt of regulatory approval from the Australian Therapeutic Goods Administration to commence the TACTI-004 trial is a significant milestone for Immutep and marks its transformation into a Phase III company. This also represents a key step towards potentially establishing a new standard of care for patients with metastatic NSCLC. We are confident based on the strength of eftilagimod alfa’s data that it can make a meaningful difference in cancer patients’ lives, and we eagerly anticipate enrolling the first patient into this important study during the first quarter of 2025," said Marc Voigt, CEO of Immutep.

Immutep has successfully completed regulatory submissions to the vast majority of the more than 25 countries that will be part of the global TACTI-004 trial. Australia represents the first approval by all regulatory authorities including ethics committees and Institutional Review Boards (IRB). The Company also anticipates full approval in the United Kingdom shortly as it has received clearances from the Medicines and Healthcare products Regulatory Agency (MHRA) and the Research Ethics Committee (REC). Additional approvals from multiple countries are expected in the weeks and months ahead.

The registrational TACTI-004 Phase III trial will evaluate eftilagimod alfa, a soluble LAG-3 protein that activates dendritic cells, in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab) and chemotherapy compared to KEYTRUDA in combination with chemotherapy and placebo in ~750 metastatic 1L NSCLC patients, regardless of PD-L1 expression. The 1:1 randomized, double-blind, multinational, controlled study, with dual primary endpoints of progression-free survival and overall survival, will include over 150 clinical sites in over 25 countries across the globe.

The Company expects to enrol the first patient in Q1 of CY2025.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.