On January 7, 2025 Nerviano Medical Sciences S.r.l. (NMS), a clinical stage company discovering and developing innovative therapies for the treatment of cancer, reported that it has entered into a clinical trial supply agreement with Roche for provision of atezolizumab (Tecentriq)1 to be combined with the Monopolar Spindle 1 (MPS1) inhibitor NMS-153, and cGAS/STING pathway activator, for the treatment of hepatocellular cancer patients (Press release, Nerviano Medical Sciences, JAN 7, 2025, View Source [SID1234649469]).

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The new study, recently approved by health authorities, is a: "Phase II Combination Study of NMS-01940153E and Atezolizumab with or without a prior priming with low dose decitabine for the Treatment of Adult Patients with Unresectable Hepatocellular Carcinoma (HCC) Previously Treated with Immune Checkpoint Inhibitors" (EUCT Number: 2024-516737-12-00).

The trial is a Phase IIa, open-label, non-randomized, 2-part multicenter study to explore the safety, tolerability, and antitumor activity of NMS-153 administered with atezolizumab to adult patients with unresectable HCC previously treated with an approved immune checkpoint inhibitor and that have experienced clinical benefit to this treatment.

NMS has recently completed the monotherapy "Phase I/II Study on Safety and Efficacy of NMS-01940153E in Adult Patients with Unresectable Hepatocellular Carcinoma (HCC) Previously Treated with Systemic Therapy" (NCT05630937), identifying early signs of clinical activity, with an adequate safety profile.

"MPS1 inhibition has been shown to be a potent upstream re-activator of the cGAS/STING pathway in multiple cancer types, including hepatocellular carcinoma. Coupling this with decitabine to reverse tumor cell epigenetic silencing of STING, along PD-L1 blockade, is an exciting novel strategy to attempt to restore immunogenicity in treatment-refractory disease", David A. Barbie, MD, Director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, Associate Professor of Medicine at Harvard Medical School, and NMS Scientific Advisory Board member commented.

"Our goal is to bring valid therapeutic options to liver cancer patients", said Hugues Dolgos, Pharm.D., Chief Executive Officer, NMS: "The combination of atezolizumab, a drug already approved for use in hepatocellular cancer, together with NMS-153, has strong potential since each has shown clinical activity in HCC2,3, bringing hope to improve outcomes for these patients. We sincerely thank Roche for their collaboration on the trial and for providing atezolizumab".

"Unmet medical need in hepatocellular cancer remains high and this novel combination with the MPS1 mechanism offers hope. NMS is committed to development of new therapies for cancer patients." according to Lisa Mahnke, MD, PhD, Chief Medical Officer, NMS.

On January 7, 2025 Asher Biotherapeutics, a biotechnology company developing precisely-targeted immunotherapies for cancer and infectious diseases, reported an agreement with AstraZeneca (LSE/STO/Nasdaq: AZN) to supply etakafusp alfa (formerly known as AB248), Asher Bio’s investigational CD8+ T cell targeted interleukin-2 (IL-2) immunotherapy, to be evaluated in combination with rilvegostomig, AstraZeneca’s investigational PD-1/TIGIT immuno-oncology bispecific antibody, in patients with advanced or metastatic NSCLC (Press release, Asher Biotherapeutics, JAN 7, 2025, View Source [SID1234649489]).

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"This exciting agreement with AstraZeneca is a reflection of the emerging clinical data from our Phase 1 study of etakafusp alfa. Initial data demonstrate a highly differentiated clinical pharmacodynamic profile with unprecedented levels of selective CD8+ T cell activation as well as initial evidence of anti-tumor effect including confirmed objective responses," said Don O’Sullivan, Ph.D., Chief Business Officer of Asher Bio. "We look forward to collaborating with AstraZeneca to expand the potential impact of our lead cis-targeted immunotherapy in patients worldwide."

As part of this agreement, AstraZeneca will sponsor and operationalize a global study to evaluate the safety and early efficacy of etakafusp alfa as a first-line treatment in combination with rilvegostomig in patients with advanced or metastatic NSCLC. Asher Bio will retain full ownership of etakafusp alfa and will supply AstraZeneca with etakafusp alfa at no cost.

About NSCLC

NSCLC is the most common type of lung cancer, accounting for 80-85% of the ~235,000 new cases in the US this year1. NSCLC originates in cells that line the airways and can invade surrounding tissues or metastasize to other parts of the body. The condition is often diagnosed at an advanced stage when it is harder to treat and is associated with a poor prognosis. Treatment options for NSCLC are tailored to the stage, subtype, and biomarker status of the disease, and may include surgery, radiation, chemotherapy, targeted therapies, immunotherapy, or a combination of these. Lung cancer has a 5-year relative survival rate of only 26.7% 2, representing a significant unmet need for additional treatment options for people living with advanced or metastatic NSCLC.

About Etakafusp Alfa (AB248)

Etakafusp alfa (AB248) is a novel CD8+ T cell selective IL-2, generated by fusing a reduced potency IL-2 mutein to an anti-CD8β antibody. It was specifically engineered to selectively and potently activate CD8+ T-cells, while avoiding natural killer (NK) cells, which can act as a pharmacological sink and contribute to toxicity, and regulatory T (Treg) cells, which are immunosuppressive. Asher Bio is currently evaluating etakafusp alfa in a Phase 1a/1b clinical trial, AB248-101. The trial consists of a dose escalation and expansion phase to investigate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of etakafusp alfa alone and in combination with pembrolizumab in subjects with locally advanced/metastatic solid tumors who failed prior therapies. Initial pharmacokinetic and pharmacodynamic data from the ongoing Phase 1a/1b clinical trial support etakafusp alfa’s proof of mechanism and activity with a highly differentiated clinical profile. Early data shows potent and selective CD8+ T cell activation without substantial changes to Treg and NK cell numbers and initial evidence of anti-tumor activity, including confirmed objective responses, with a generally well-tolerated safety profile. Please refer to www.clinicaltrials.gov (NCT05653882) for additional details related to this Phase 1a/1b clinical trial.

On January 7, 2025 Pluristyx, a leading provider of Good Manufacturing Practices (GMP), cutting-edge, induced pluripotent stem cell (iPSC) technologies, reported the immediate availability of the PSXi013 iPSC line made under GMP (Press release, panCELLa, JAN 7, 2025, View Source [SID1234649470]). This off-the-shelf, readily available cell line will revolutionize the cell and gene therapy landscape, breaking the mold of how cells are supplied, and offering an unprecedented solution for researchers and developers seeking to accelerate clinical translation of their iPSC-based therapies.

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Avoiding many of the pitfalls associated with conventional iPSC reprogramming methods that can introduce genetic instability, PSXi013 has been reprogrammed using our state-of-the-art, footprint-free natural-nucleotide, mRNA technology. This innovative approach eliminates the risk of insertional mutagenesis and incorporation of synthetic nucleotides into the genome, ensuring the highest quality and safety for therapeutic applications. As the lowest passage iPSC bank available on the market (delivered at Passage 10), PSXi013 effectively minimizes the risk of genetic drift, allows the customer to select a clone on their schedule, and provides a more stable and clinically relevant starting material versus higher passage cell banks. PLSXi013 is available for immediate licensing with a simplified structure directly through Pluristyx.

"We are thrilled to launch PSXi013, a true game-changer in the field of regenerative medicine," said Dr. Benjamin Fryer, Chief Executive Officer of Pluristyx. "We have already licensed this line to several leading therapeutic developers and are excited to now share this new line with the wider industry. PSXi013 embodies our commitment to the most advanced, reliable, and clinically relevant iPSC solutions. We are empowering researchers to dramatically accelerate the development of their life-changing cell therapy with our unmatched quality, low passage number, potential for genetic modification, and robust regulatory support. "

PSXi013 is manufactured from a healthy adult donor consented under IRB approved protocols, and has been rigorously tested to meet or exceed regulatory guidelines for clinical use in all major global regulatory jurisdictions and indications.

Key features of the stem cell line that set it apart:

Prospectively designed for genetic editing and process optimization: PSXi013 is available in polyclonal format unlike all other current lines where a clone is automatically preselected by the supplier. Polyclonal iPSC pools eliminate genetic bottlenecks and enable end users to edit and/or select their cells for desired phenotype and process functionality.

Unmatched Quality and Genomic Integrity: Extensive testing, including extended serial passaging, confirms the exceptional genomic stability of PSXi013, making it an ideal foundation for large-scale, consistent clinical manufacturing.

Streamlined Regulatory Pathway: The GMP PSXi013 iPSC line will be supported by a Drug Master File (DMF) submission to the US FDA to simplify the Investigational New Drug (IND) application process and accelerate clinical trial initiation.

Proven Differentiation Potential: PSXi013 demonstrates robust differentiation potential across a wide array of therapeutically relevant cell types, including but not limited to beta islets, hepatocytes, cardiomyocytes, Natural Killer (NK) cells, mesenchymal stem/stromal cells (MSCs), and neuronal progenitors. This versatility makes it a powerful tool for developing treatments for a broad spectrum of diseases.

Addressing key safety concerns surrounding iPSC-based therapies, such as immunogenicity and uncontrolled proliferation, Pluristyx also offers custom manufacturing of genetically modified variants of PSXi013. These variants can incorporate hypoimmune technology to evade immune rejection, and Pluristyx’s proprietary FailSafe suicide switch technology to selectively eliminate proliferating cells, enhancing the manufacturability, safety, and efficacy of the final cell therapy product. Hypoimmune and FailSafe edits are currently available in iPSC lines for preclinical research and development and can be performed under GMP conditions upon request.

The launch of the GMP PSXi013 iPSC Master Cell Bank marks a pivotal moment in Pluristyx’s ongoing mission to accelerate the development of stem cell therapies. By providing a high-quality, low-passage iPSC line backed by comprehensive testing and regulatory support, Pluristyx is empowering researchers and developers to bring tomorrow’s cell therapies to patients today.

Pluristyx CEO Benjamin Fryer will be presenting the company and hosting one-on-one meetings during the JP Morgan Healthcare Conference in San Francisco next week.

On January 7, 2025 Verismo Therapeutics, a clinical-stage biotechnology company developing the novel KIR-CAR platform for solid tumors and blood cancers, reported a strategic investment from the Institute for Follicular Lymphoma Innovation (IFLI), a global non-profit foundation dedicated to advancing treatment options for follicular lymphoma (FL) (Press release, Verismo Therapeutics, JAN 7, 2025, View Source [SID1234649487]). This partnership aims to enhance Verismo’s SynKIR-310 pipeline and provide catalytic investment for the pipeline’s FL arm, accelerating the development of next-generation cell therapies that address high unmet medical needs.

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The investment from IFLI will help advance Verismo’s SynKIR-310 pipeline, which aims to treat FL along with other non-Hodgkin lymphoma (NHL) subtypes. IFLI’s deep expertise in FL will be crucial in guiding Verismo through FL-specific clinical considerations and aiding in patient recruitment.

"We are thrilled to receive this strategic investment from IFLI, which shares our vision for developing transformative therapies for patients suffering from aggressive tumors and lymphomas," said Bryan Kim, CEO of Verismo Therapeutics. "This funding will enable us to expedite the clinical development of our SynKIR-310 program, which is currently in Phase 1 clinical trial. IFLI’s support will enable us to bring our novel therapies to FL patients more quickly and efficiently."

Verismo Therapeutics is currently running a multicenter, open-label study of a single infusion of SynKIR-310 in participants with post-CAR T and CAR-naive relapsed/refractory B-NHL (NCT06544265), including FL. This clinical study is a basket trial in B-NHL subtypes. The design includes two dose levels and an expansion cohort at the Recommended Phase 2 Dose (RP2D), with a total enrollment of up to 18 patients. With IFLI’s investment totaling up to $4,050,000 over 3 years, Verismo aims to expand the number of FL-focused clinical sites to enroll more FL patients.

"IFLI is excited to support the next wave of transformative cell therapies with Verismo lead SynKIR-310 targeting CD19," said Michel Azoulay, MD, MBA, Chief Medical Officer of IFLI. "We expect that positive Phase 1safety and preliminary efficacy data will support accelerated clinical development in FL for patients not responding to first line immunotherapy as well as exploration in additional NHL."

IFLI has a proven track record of advancing lymphoma treatments through strategic funding and collaborative partnerships, including its support for groundbreaking research at Washington University in St. Louis, which leverages ctDNA sequencing to improve the understanding and treatment of FL.

On January 7, 2025 Alloy Therapeutics Inc. ("Alloy"), a biotechnology ecosystem company dedicated to democratizing access to cutting edge drug discovery technologies, reported a target specific collaboration and license agreement for the use of their novel and proprietary AntiClastic Antisense Platform with Sanofi for a central nervous system (CNS) target (Press release, Alloy Therapeutics, JAN 7, 2025, View Source [SID1234649453]). In return, Sanofi will provide Alloy with upfront license fees and near-term preclinical milestone payments up to $27.5 million. Alloy will also be eligible to receive discovery, development, and commercial milestone payments of over $400 million, as well as tiered royalties on sales of any products resulting from the collaboration. This collaboration underscores a shared commitment to advancing innovative therapeutics in the CNS space.

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Alloy’s AntiClastic Antisense platform allows drug developers to realize the true potential of antisense therapeutics by reaching intracellular disease targets at the RNA level. The platform addresses limitations of current antisense chemistries relating to therapeutic index. This technology platform was launched by Alloy in 2023 after exclusively licensing its underlying intellectual property which implements a novel spatial conformation of the oligonucleotide developed by Sudhir Agrawal of Arnay Sciences.

"At Alloy Therapeutics, we’re transforming RNA therapeutics by bridging foundational insights with modern innovation," said Vinod Vathipadiekal, Chief Scientific Officer, Genetic Medicines at Alloy Therapeutics. "Our work on the AntiClastic Antisense platform and the data generated is pushing the technology beyond current standards and driving innovation that has the potential to redefine what’s possible in RNA therapeutics. With the capabilities we have built and validated, we are excited to work with Sanofi, and we look forward to continuing to deliver on Alloy’s commitment to open collaboration and accessible technologies to ensure these breakthroughs can drive the development of superior RNA-based therapies for patients."

Through the collaboration, Sanofi will leverage their neuroscience expertise and collaborate with Alloy to use the AntiClastic Antisense platform for delivery of therapeutics to the brain, aiming to develop a novel class of genetic medicine capable of crossing the blood-brain barrier.

"We’re excited to partner with Sanofi, a global leader in healthcare innovation, on this landmark licensing agreement for our AntiClastic Antisense platform," said Errik Anderson, Alloy Therapeutics CEO and Founder. "When we began working with Dr. Agrawal, a renowned leader in antisense therapeutics, to integrate his groundbreaking work into Alloy’s genetic medicines platform, we were confident in its potential to revolutionize antisense drug development and reshape the broader drug discovery landscape. This collaboration exemplifies Alloy’s adaptable, multi-modality approach, providing our partners with a comprehensive suite of discovery solutions and access to novel platforms to accelerate the development of the most effective therapies for patients in need."