On August 26, 2024 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported an article in Molecular Therapy demonstrating TALEN -mediated gene editing capabilities for design of SMART DUAL CAR T-cells, which efficiently target immunotherapy recalcitrant solid tumors while mitigating potential safety risks (Press release, Cellectis, AUG 26, 2024, View Source [SID1234646092]).

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Adoptive cell therapy based on CAR T cells has proven to be lifesaving for many cancer patients. However, its therapeutic efficacy has so far been restricted to only a few malignancies, with solid tumors proving to be especially recalcitrant to efficient therapy.

One key factor for this are cancer-associated fibroblasts (CAFs), that modulate the tumor microenvironment (TME) to inhibit T cell infiltration and induce T cell dysfunction. Additionally, the sparsity of tumor-specific antigens (TSA) and expression of CAR-directed tumor-associated antigens (TAA) on normal tissues often results in on-target off-tumor cytotoxicity, raising safety concerns.

Using TALEN gene editing technology, Cellectis presents an innovative CAR T cell engineering strategy designed to overcome these challenges. Our allogeneic SMART CAR T-cells are designed to express a constitutive CAR, targeting FAP+ CAFs in solid tumors, and a second inducible CAR, expressed only in the presence of FAP+ CAFs and targeting the tumor associated antigen (TAA) named mesothelin. The resultant SMART Dual CAR T-cells efficiently infiltrate and efficiently target triple-negative breast tumors in physiologically relevant mice models, with no observable on-target, off-tumor toxicity.

"The adaptations of this approach could resolve several key challenges for CAR T-cell therapy against solid tumor-low CAR T-cell infiltration, immuno-suppressive microenvironment, antigen heterogeneity as well as on target, off-tumor toxicity. This strategy thus has significant implications for successful therapeutic development of CAR T-cells against solid tumors" said Shipra Das, Ph.D., Associate Director Immuno-Oncology and Innovation Program Management at Cellectis.

On August 26, 2024 Opna Bio reported that it has dosed the first patient with OPN-6602, a potent and selective EP300/CBP bromodomain inhibitor, in a Phase 1 clinical study in multiple myeloma (Press release, Opna Bio, AUG 26, 2024, View Source [SID1234646108]). The trial is expected to enroll up to 130 total patients with relapsed or refractory multiple myeloma at sites in the U.S. Multiple myeloma is a type of blood cancer derived from malignant plasma cells in the bone marrow. There are approximately 180,000 people worldwide who are diagnosed with multiple myeloma and 117,000 deaths attributable to the disease annually.

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The first patient was dosed at The START Center for Cancer Research in Grand Rapids, Michigan, with Dr. Andrew Sochacki, principal investigator, leading the study team. "OPN-6602 represents an exciting and novel therapeutic target that will provide a much-needed option for our relapsed and refractory myeloma patient population," stated Dr. Sochacki. "The innovative approach of this therapy has the potential to significantly improve outcomes for patients who have exhausted other treatment options. This collaboration with Opna underscores our commitment to advancing cutting-edge research and delivering new, effective therapies to patients who need them the most."

OPN-6602 is an oral, small molecule inhibitor of the E1A binding protein (EP300) and CREB-binding protein (CBP). Through EP300/CBP inhibition, OPN-6602 down regulates expression of IRF4 and MYC, two transcription factors that drive growth of multiple myeloma cells. Preclinical data presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) 2024 Annual Meeting showed that OPN-6602 significantly reduced tumor growth as a single agent (71% tumor growth inhibition) in the OPM-2 human multiple myeloma cell xenograft model as well as increased anti-tumor activity (>100% tumor growth inhibition) in combination studies.

"We are pleased to initiate clinical testing of OPN-6602, which has shown potent anti-tumor activity in multiple myeloma models as well as other cancers," said Reinaldo Diaz, MBA, chief executive officer.

The objectives of the open-label study are to assess safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of OPN-6602 as monotherapy and in combination with dexamethasone in patients with relapsed or refractory multiple myeloma. The company expects to enroll up to 90 patients in the dose-escalation cohort, with an additional 40 patients in the dose-expansion cohort. The completion date is expected in the second half of 2026.

Company Appoints Industry Experts to Board of Directors

Additionally, Opna announced the appointments of Axel Bolte, MBA, MSc, to board director and Stephanie Oestreich, PhD, MPA, to board observer, following the Myeloma Investment Fund’s recent investment in Opna. The Myeloma Investment Fund is the philanthropic investment fund of the Multiple Myeloma Research Foundation.

Mr. Bolte most recently served as founder, president and CEO of Inozyme Pharma (INZY), a rare disease company where he continues as director and advisor. He also served as a board director of IVERIC Bio (ISEE) until its sale to Astellas. Mr. Bolte is managing partner for Healthcare Advisors GmbH and was previously venture partner and investment advisor for HBM Partners AG, while serving on multiple boards of private and public companies.

Dr. Oestreich, the managing director of the Myeloma Investment Fund, brings decades of experience, previously serving as chief business officer at Galecto, vice president at Mnemo Therapeutics, as well as venture partner at RA Capital. She was also executive vice president at Evotec where she built its North American investment arm and started an incubator with Samsara BioCapital, as well as worked in business development and commercial functions at Roche and Novartis.

"We welcome Axel Bolte and Dr. Stephanie Oestreich to our board, both of whom bring valuable hands-on experience in industry operations, disease areas, financing and business development," said Diaz.

On August 26, 2024 Delcath Systems, Inc. (Nasdaq: DCTH) ("Company" or "Delcath"), an interventional oncology company focused on the treatment of primary and metastatic liver cancers, reported the publication of an independent study conducted by investigators at the University Hospital of Leipzig, Germany, in the European Society for Medical Oncology journal of Gastrointestinal Oncology (Press release, Delcath Systems, AUG 26, 2024, View Source [SID1234646093]). The study, titled "Hepatic chemosaturation with melphalan in patients with primary or secondary liver tumors with or without extrahepatic tumor manifestation," highlights the efficacy and safety of repeated chemosaturation treatments using Delcath’s CHEMOSAT Hepatic Delivery System.

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Key Findings from the Independent Study:

Patient Population: This retrospective study evaluated the efficacy of CHEMOSAT in 33 previously treated patients with unresectable intrahepatic metastases from various cancers: uveal melanoma (N=19), cholangiocarcinoma (N=8), hepatocellular carcinoma (N=2), and one patient each with ciliary body melanoma, acinar cell carcinoma, pancreatic cancer, or tonsil cancer (N=4). In addition to hepatic metastases, 7 out of 33 patients also had limited extrahepatic disease, which was found not to significantly impact overall survival.
Disease Control Rate: The study reported a disease control rate (DCR) of 91%, with 30 out of 33 patients experiencing either objective tumor response or stable disease. Notably, 6 patients (18.2%) achieved complete response (CR) in the liver, including 5 patients with uveal melanoma and 1 patient with cholangiocarcinoma, who received a median of 5 treatment cycles.

Hepatic Progression-Free Survival: Median hepatic progression-free survival (hPFS) was 52 weeks across all patients, with particularly strong outcomes for specific cancers:
69 weeks (16 months) median hPFS in patients with uveal melanoma.
38 weeks (8.5 months) median hPFS in patients with cholangiocarcinoma.
Importance of Repeated Treatments: The investigators’ approach of using CHEMOSAT in the form of regularly repeated treatment cycles as clinically indicated (Figure 1), similar to systemic chemotherapy, resulted in long-term disease control in the majority of patients and was well tolerated.
Tolerability and Safety: The safety profile of CHEMOSAT was consistent with published literature. Most patients experienced transient hematological adverse events, which were routinely managed with supportive care. Importantly, no significant liver damage was reported, even in patients who underwent multiple treatment cycles. Treatment was discontinued in 2 patients due to adverse events, and 2 patients withdrew consent during the treatment period.

Dr. Vojislav Vukovic, Chief Medical Officer of Delcath Systems, commented, "The results of this independent study reinforce the potential of our CHEMOSAT Hepatic Delivery System as an essential tool in the management of primary and secondary liver tumors, particularly for patients with limited treatment options. The high rate of disease control observed, even in patients with extrahepatic tumor spread, underscores the importance of continuing to explore and refine this treatment approach in larger, prospective trials."

On August 26, 2024 Diakonos Oncology Corp., a clinical-stage immuno-oncology company, reported the final closing of an oversubscribed seed financing of $11.4 million (Press release, Diakonos Oncology, AUG 26, 2024, View Source [SID1234646109]). The round was led by biotechnology investment firm Restem Group Inc., with participation from existing investors.

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To date, funds have enabled the company to establish manufacturing operations, add key leadership positions, and complete enrollment for the Phase 1 study of lead asset DOC1021 in the treatment of glioblastoma (GBM). The additional capital will fund operations into late 2025 and allow Diakonos to initiate the Phase 2 trial in GBM prior to closing a Series A round.

"We greatly appreciate the support of these investors in sharing our passion for improving the lives of patients suffering from deadly cancers such as glioblastoma," said Mike Wicks, Diakonos CEO. "The fact that this financing is nearly triple our initial target also shows they share our confidence in the effectiveness of our unique cancer therapy. This investment will fund operations through the final readout of key safety and efficacy data from our Phase 1 trial and will allow the company to ramp up preparations for pipeline expansion and the initiation of our Phase 2 GBM trial which is expected to begin in the fourth quarter of this year."

"We are thrilled to invest in this groundbreaking company that is at the forefront of cancer treatment innovation. As a firm deeply involved in the cell therapeutic field, we recognize the immense potential of their pioneering work with dendritic cell therapies and we are confident that this can become a new standard of care for cancer in the future," said Andres Isaias, Executive Chairman of Restem Group Inc.

About DOC1021

DOC1021 is a first-of-its-kind dendritic cell vaccine (DCV) that initiates a complete cytotoxic TH1 immune response against a patient’s cancer through our proprietary double loading technology. Enrollment in the two-year Phase 1 trial was completed in December 2023.

In addition to the lead GBM study, two other clinical trials of Diakonos’ DCV are ongoing for the treatment of pancreatic cancer and angiosarcoma. Diakonos has received Fast Track designations from the FDA for both the GBM and pancreatic cancer programs. The company has also received Orphan Drug Designation for the GBM program.

Diakonos’ DCVs activate robust cytotoxic TH1 cell signaling pathways that better harness a patient’s immune system to target and eliminate cancer cells. This is achieved without any genetic modification of the patient’s immune cells and without the need for toxic preconditioning.

On August 26, 2024 Genmab A/S (Nasdaq: GMAB) reported that its Chief Executive Officer Jan van de Winkel, Ph.D. and Chief Financial Officer Anthony Pagano will participate in a fireside chat at the Morgan Stanley 22nd Annual Global Healthcare Conference at 1:05 PM EDT / 7:05 PM CEST on September 4, 2024 (Press release, Genmab, AUG 26, 2024, View Source [SID1234646094]). A webcast of the event, which will include brief opening remarks followed by a question-and-answer session, will be available on Genmab’s website at View Source

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