On March 26, 2024 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of Antibody Radiation Conjugates (ARCs) and other targeted radiotherapies, reported that the University of Texas Southwestern Medical Center (UT Southwestern) will lead a clinical trial studying Actinium’s Iomab-ACT, a targeted radiotherapy conditioning agent prior to patients receiving an FDA approved commercial CAR T-cell therapy (Press release, Actinium Pharmaceuticals, MAR 26, 2024, View Source [SID1234641458]). UT Southwestern will start recruiting patients following FDA’s review and clearance of the study. CAR T-cell therapy utilizes patients’ own immune cells called T-cells, which are engineered to include a chimeric antigen receptor and then reinfused into the patient to recognize and destroy cancer cells. Currently, there are six CAR-T therapies approved to treat patients with leukemias, lymphomas and multiple myeloma that collectively reached sales in 2023 exceeding $3.5 billion.

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Actinium developed Iomab-ACT with the goal of replacing the chemotherapy conditioning regimens currently used prior to cell and gene therapies. Early clinical data with Iomab-ACT conditioning prior to CAR-T demonstrates its ability to produce targeted lymphodepletion along with negligible incidences of immune effector cell-associated neurotoxicity syndrome (ICANS) or cytokine release syndrome (CRS), which are the major toxicities observed with the current chemotherapy based conditioning regimens, which are suboptimal and can limit patients from CAR-T access and may result in poor outcomes.

Sandesh Seth, Actinium’s Chairman and CEO, stated, "This is a pivotal moment for our Iomab-ACT program that presents the opportunity to produce potential practice changing clinical data. Cellular therapies such as CAR-T and gene therapies represent a multi-billion market opportunity with an expectation of nearly doubling to reach approximately 93,000 patients annually in the U.S. alone by 2030. We believe Iomab-ACT can be a universal conditioning regimen based on its potential to reduce CAR-T related toxicities such as ICANS and CRS, as evidenced by our early clinical work with a novel CD19 CAR T-cell therapy and may improve patient access and outcomes by eliminating the need for the non-targeted chemotherapy-based conditioning that are currently required prior to CAR-T therapies. This trial is a clear demonstration of Actinium’s commitment to being at the forefront of applying targeted radiotherapy to innovative applications and novel indications."

Dr. Avinash Desai, Actinium’s Chief Medical Officer, added, "Cellular therapies like CAR-T have transformed outcomes for tens of thousands of patients but clinicians continue to be frustrated with the need to use chemotherapy for conditioning. We are excited to be collaborating with the team at UT Southwestern on this first ever trial to study Iomab-ACT with a commercial CAR-T. Given the extensive data with CAR-T therapies, ­results from this study can allow us to show the impact of Iomab-ACT on reducing CAR-T related toxicities such as ICANS and CRS and improving efficacy including persistence of CAR-T cells, rates of response, and other efficacy outcomes. Based on the initial results from our clinical trial with Memorial Sloan Kettering’s CD19 CAR-T therapy, we are looking forward to initiating this study and delivering clinical proof of concept data with a commercial CAR-T."

Ongoing Iomab-ACT Phase 1 CAR-T Conditioning Results

Actinium presented results from its ongoing phase 1 trial using Iomab-ACT as conditioning prior to CD19 CAR-T therapy for patients with relapsed or refractory B-cell Acute Lymphoblastic Leukemia (B-ALL) or Diffuse Large B-cell Lymphoma (DLBCL) at the Tandem Meetings I Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR the combined annual meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood & Marrow Transplant Research (CIBMTR) in February 2024. Importantly, no patients (0/4) developed immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade, a major safety measure of the study, as ICANS is observed in 25% or more of pts w/ R/R B-ALL and DLBCL treated with various CAR T-cell products and minimal CRS. Iomab-ACT demonstrated transient depletion of peripheral blood lymphocytes and monocytes. Persistence of CAR T-cells up to 8 weeks and minimal non-hematologic toxicities have been observed to date.

Targeted Radiotherapy Conditioning Opportunity

The opportunity exists for better conditioning in other areas of cellular therapy, such as CAR-T as well as gene therapies. The pipeline of CAR-T and gene therapies has rapidly expanded, with the addressable patient population expected to nearly double and reach approximately 93,000 patients in the U.S. by 2030 based on the current pipeline of cellular therapies. The CAR-T market size in terms of revenue is estimated to grow at a CAGR of approximately 11% over the next 5 plus years. Currently, there are six CAR T-cell therapies approved by the FDA that are used to treat patients with lymphomas, leukemia, and multiple myeloma, which collectively had total sales of over $3.5 billion in 2023. The addressable market for Iomab-ACT is in line with the patient population for cell and gene therapies as all patients receive conditioning of some type prior to these treatments. We will continue to develop Iomab-ACT, our next-generation conditioning program for rapidly growing cell and gene therapies based on early promising results, ultimately with the value proposition of improving overall access and outcomes for patients who need cellular or gene therapies. A potential blockbuster revenue opportunity exists for Iomab-ACT assuming it can provide one or more clinical benefits related to lower CRS, less ICANS, longer duration of response or a higher overall success rate of cellular therapy due to benefits of targeted conditioning.

On March 26, 2024 Volastra Therapeutics, a clinical-stage biotechnology company, reported partnerships with Microsoft, Function Oncology and Tailor Bio with the goal of broadening the potential of its evolving therapeutics pipeline across a large number of tumor types through identification of predictive biomarkers (Press release, Volastra Therapeutics, MAR 26, 2024, View Source [SID1234641454]).

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Volastra leads the field in development of therapeutics that target chromosomal instability (CIN), a key characteristic of cancer associated with accelerated disease progression, increased resistance to therapies, and shortened patient survival. While CIN is a hallmark of cancer, levels of CIN vary widely across tumor types from being nearly ubiquitous in some to only partially present in others.

Volastra’s two KIF18A inhibitors are in parallel Phase 1 clinical trials treating tumor types with near-universally high levels of CIN. Significant potential remains in many other tumor types, for which a biomarker-defined approach may be able to identify subsets of patients most likely to benefit from treatment.

"Predictive biomarkers can help us expand the reach of our therapies to as many patients as possible," said Charles Hugh-Jones, M.D., FRCP, CEO at Volastra. "By leveraging the diverse expertise of our partners, we believe we can achieve this even in cancers with heterogenous levels of CIN."

Volastra has collaborated with Microsoft Research since 2020 to develop image-based artificial intelligence (AI) models that quantify CIN in patient samples.

"Our collaboration has shown extraordinary progress in creating AI techniques to identify visual hallmarks of CIN with high levels of accuracy, a process that is incredibly difficult and expensive for humans to do alone," commented Jonathan Carlson, Ph.D., Managing Director, Microsoft Research Heath Futures. "We are thrilled to continue to combine our research expertise with Volastra’s so they may amplify their impact and reach more patients."

This novel visual approach will now be complemented by the unique and distinct expertise of Function Oncology and Tailor Bio, both recognized leaders in precision medicine.

"Function’s collaboration with Volastra integrates our unique CRISPR platform to decipher patient-specific drug target vulnerabilities," said Srinath Sampath, M.D., Ph.D., M.Phil., co-founder and CEO of Function Oncology. "Our platform allows us to reach ground-state genetic truth about target dependence in cancer and beyond, and we look forward to applying this technology to Volastra’s clinical programs."

Jason Yip, MBA, co-founder and CEO of Tailor Bio commented, "Our latest Nature publication demonstrated the remarkable potential for genomic CIN signatures to quantify unique aspects of chromosomal instability. We are excited to apply our proprietary precision medicine platform to clinical trials in the rapidly advancing field of KIF18A inhibition."

On March 26, 2024 Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that the U.S. Food and Drug Administration (FDA) has granted Priority Review for its New Drug Application (NDA) for revumenib, the Company’s first-in-class menin inhibitor, for the treatment of adult and pediatric relapsed or refractory (R/R) KMT2A-rearranged (KMT2Ar) acute leukemia (Press release, Syndax, MAR 26, 2024, View Source [SID1234641453]). The NDA filing is being reviewed under the FDA’s Real-Time Oncology Review Program (RTOR) and has been assigned a Prescription Drug User Fee Act (PDUFA) target action date of September 26, 2024. RTOR allows for a more efficient review and close engagement between the sponsor and the FDA throughout the submission process, which historically has led to earlier approvals.

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"The receipt of Priority Review for the revumenib NDA filing is a significant milestone as we transition to a leading commercial-stage oncology company with the planned launches of two first- and best-in class drugs in 2024," said Michael A. Metzger, Chief Executive Officer. "With two regulatory filings now under FDA Priority Review, our team is focused on commercial preparations to enable Syndax’s continued success as we enter this next stage of growth."

The NDA submission is supported by positive data from the pivotal AUGMENT-101 trial of revumenib in adult and pediatric patients with KMT2Ar acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). As previously reported, the trial met its primary endpoint at the protocol-defined interim analysis with a complete remission (CR) or a CR with partial hematological recovery (CRh) rate of 23% (13/57; 95% confidence interval [CI]: [12.7, 35.8, one-sided p-value = 0.0036]) among the 57 efficacy evaluable patients in the pooled KMT2Ar acute leukemia population. 70% of patients who achieved a CR/CRh and were assessed for minimal residual disease (MRD) were MRD negative. Additionally, 63% (36/57) of the efficacy-evaluable patients achieved an overall response, 39% (14/36) of whom underwent hematopoietic stem cell transplant (HSCT), with 50% (7/14) restarting revumenib as post-transplant maintenance at the time of the data cutoff.

About Revumenib

Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged, also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and NPM1-mutant AML. Positive topline results from the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint were presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and data from the Phase 1 portion of AUGMENT-101 in acute leukemia was published in Nature. Revumenib was granted Orphan Drug Designation by the FDA and European Commission for the treatment of patients with AML and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted Breakthrough Therapy Designation (BTD) by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

About Real-Time Oncology Review (RTOR)

RTOR provides a more efficient review process for oncology drugs to ensure that safe and effective treatments are available to patients as early as possible, while improving review quality and engaging in early iterative communication with the applicant. Specifically, it allows for close engagement between the sponsor and the FDA throughout the submission process and it enables the FDA to review individual sections of modules of a drug application rather than requiring the submission of complete modules or a complete application prior to initiating review. Additional information about RTOR can be found at: View Source

On March 26, 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 topline data from the Phase 2a study of SLS009 and provides an update on Phase 3 REGAL Study of GPS in AML (Press release, Sellas Life Sciences, MAR 26, 2024, View Source [SID1234641452]). The Company will host a webinar to discuss the data and the REGAL update today at 8:15 am ET.

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"Completion of enrollment in the Phase 3 REGAL trial represents an important milestone in our goal to deliver GPS to AML patients," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "We are extremely grateful to the patients, their families, and investigators who have helped us achieve this significant milestone. Additionally, we are pleased to share that the Steering Committee has reviewed the study as of the March 1, 2024, cutoff date. As of this evaluation, 123 patients were enrolled with 66 of them discontinuing the treatment. In the trial, patients are recorded as having stopped the study treatment in cases of death for any reason, relapse, intolerable toxicity, or treatment completion. Regarding the GPS arm, we are pleased to report that we have not observed any intolerable toxicities in any patient population across all our clinical studies thus far, although toxicities are commonly observed with therapies used in the control arm. Therefore, almost all patients who are off treatment may have most likely either relapsed or passed away. The most frequent cause of death in this patient population is relapse. As the study sponsors, we lack specific information on the outcomes of these 66 patients, hindering our ability to confirm whether the required number of events for interim analysis – 60 – has been reached. The determination of such outcomes, the primary endpoint of the trial, lies within the purview of the IDMC, which is now scheduled to meet by the end of April."

The REGAL Steering Committee met on March 22, 2024, to discuss the study and believes the high number of patients who completed participation in the study signals that the interim analysis requiring 60 events may be imminent. The Committee also expressed its satisfaction with SELLAS’ overall clinical study conduct and complimented SELLAS for addressing such a debilitating and high unmet medical need as no drugs are approved in the AML CR2 maintenance setting.

Dr. Stergiou continued: "We are extremely excited to share positive topline data from the Phase 2a trial of SLS009 in AML patients resistant to venetoclax combination therapies. In the selected optimal dose regimen of 30 mg BIW a 50% response rate was achieved, far surpassing the targeted 20% rate. Notably, we identified promising biomarkers and observed a 100% response rate at the optimal dose level and a 57% response rate across all the levels tested in patients with those biomarkers. The SLS009 aza-ven treatment was well-tolerated and evoked anti-leukemic effects in 67% of patients across all levels dosed. The first patient who achieved a complete response continues on the study and remains leukemia-free 9 months post-enrollment. These compelling results from the Phase 2a reinforce our belief that SLS009 represents a potential breakthrough for relapsed and/or refractory AML patients, addressing one of the most urgent unmet medical needs."

Summary of Topline Data from Phase 2a data of SLS009 in AML

Patients Characteristics

As of March 15, 2024 data cutoff, 21 patients were treated
All patients were diagnosed with AML refractory to or relapsed after venetoclax containing regimens
20 out of 21 (95%) enrolled patients had adverse/high-risk cytogenetics and 1 patient (5%) had intermediate cytogenetics
Median age was 70 and 19/21 (90.5%) of patients were older than 60
Safety

SLS009 in combination with aza/ven has been well-tolerated at all tested dose levels
No dose-limiting toxicities (DLT) at any of the studied dose levels and no treatment-related high-grade (≥G3) toxicities were observed
Hematologic toxicities profile was consistent with aza/ven standalone treatment

Efficacy

A total of 21 patients were enrolled in the study as of March 15, 2024: 10 in the 45 mg safety cohort, 11 in the 60 mg cohort (2 x 30 mg twice a week or 60 mg once a week)

10% response rate in the 45 mg QW safety cohort (dose level below the recommended Phase 2 dose, RP2D)
20% response rate in the 60 mg QW cohort
50% response rate in the 60 mg, 2 x 30 mg BIW cohort
Observed strong anti-leukemic activity, defined as 50% or more bone marrow blast reduction in 67% of patients across all dose levels
Median survival rate has not been reached in any of the dose levels
The first patient enrolled in the study who achieved a complete response (CR) continues on the study and remains leukemia-free 9 months after enrollment
Biomarkers

During the trial the Company identified potential biomarkers currently undergoing testing as predictive markers in the most recent portion of the study
Patients with the identified biomarkers exhibited significantly higher response rates:
100% response rate at the optimal dose level (30 mg BIW)
57% response rate across all dose levels
Furthermore, the Company has clarified the proposed biological basis and mechanism of action for SLS009 activity in patients with these biomarkers
The relevant biomarkers are present in multiple hematologic and solid cancer indications, with a substantial proportion of patients exhibiting them in additional indications, ranging up to ~50% of patients in some indications
The Phase 2a clinical trial of SLS009 is an open-label, single-arm, multi-center study designed to evaluate the safety, tolerability, and efficacy of SLS009 in combination with aza/ven at two dose levels, 45 and 60 mg. In the 60 mg dose cohort patients were randomized into either a 60 mg dose once per week or a 30 mg dose two times per week. The target response rate at the optimal dose level is 20% with a target median survival over 3 months. In addition, the study aims to identify biomarkers for the target patient population and enrichment for further trials.

On March 26, 2024 The Swedish biotech company Neogap Therapeutics reported to have received SEK 5 million from Eurostars in a collaboration project with the French biotech company Okomera (Press release, Neogap Therapeutics, MAR 26, 2024, View Source,c3951209 [SID1234641451]). The funding aims to enhance the development of an analysis method for T-cell activity against the patient’s tumour.

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Neogap is developing pTTL, personalised Tumour Trained Lymphocytes, a tailored cell therapy that utilises modified proteins, known as neoantigens, to activate the immune system specifically against cancer cells. The therapy is currently being assessed in phase I/II clinical trials for the treatment of colorectal cancer.

As part of the Eurostars-funded project, Neogap collaborates with the French biotech company Okomera, which has developed an innovative method to analyse cell interactions. The method allows for the analysis of how T-cells kill tumour cells in what is known as a killing assay, requiring only a minimal quantity of the cell product. This analysis is set to deepen the understanding of the interactions between T-cells and tumour cells, potentially enabling predictions about the efficacy of Neogap’s cell therapy products. The goal is to develop a system that can easily and reliably measure the capability of Neogap’s T-cell product, pTTL, in eradicating cancer cells.

"We are very grateful for Eurostars’ backing, which not only recognises the scientific potential of our company but also reinforces our role as an innovator in analysis methods for next-generation cell therapies. The funding enables further research that is essential for advancing our cell therapy product to later clinical phases," says Samuel Svensson, CEO of Neogap Therapeutics.

"Through our collaboration with Neogap, we’re afforded the opportunity to integrate Okomera’s technology into developing analytical methods for their pioneering cancer therapies. We eagerly anticipate the advancements this partnership will bring to the field of precision medicine," says Sidarth Radjou, CEO of Okomera.