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 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 Interius BioTherapeutics, a clinical-stage company engineering targeted, programmable vectors for the precision delivery of genetic medicines, reported that the German regulatory agency, the Paul Ehrlich Institute (PEI), has approved expansion of the INVISE first-in-human Phase 1 clinical trial evaluating INT2104 for the treatment of B-cell malignancies to Europe (Press release, Interius BioTherapeutics, JAN 7, 2025, View Source [SID1234649468]). INVISE is the first clinical trial to announce clearance to evaluate in vivo CAR gene therapy in Europe. INT2104 is a first-in-class gene therapy that delivers a CAR transgene to generate effector CAR-T and CAR-NK cells in vivo for the targeting of CD20-positive B cells.

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"We are thrilled to have received approval from PEI regulators to expand our INVISE clinical study into the EU," said Interius President and CEO, Phil Johnson, M.D. "The PEI has a rich history in supporting the advancement of novel medicines, including foundational research for in vivo CAR T therapy, and this approval highlights the strength of our preclinical data and the breakthrough potential of INT2104 to broaden access to CAR therapies. We are also thankful for our Australian clinical sites that have paved the way for our continued expansion, having recently dosed our first study participant there in October. We remain committed to transforming the current treatment paradigm through clinical evaluation of our novel products, and the PEI’s approval marks a significant step."

Dr. Marion Subklewe, M.D., Ph.D., full professor and consultant in the Department of Hematology of the LMU University Hospital, head of the Cellular Immunotherapy program and head of the Laboratory for Translational Cancer Immunotherapy at the Ludwig-Maximillian University in Munich, and INVISE Principal Investigator, added, "I am honored to collaborate with the Interius team to bring their innovative in vivo CAR gene therapy to patients in Germany and other European countries. Cancer is an incredibly complex disease that demands bold and creative solutions. Interius’ groundbreaking approach has the potential to simplify treatment, provide faster and more accessible care, and significantly improve patient outcomes while transforming the treatment journey by reducing delays and eliminating complicated procedures."

About INVISE
INVISE (INjectable Vectors for In Situ Engineering) is a first-in-human Phase 1 clinical trial evaluating the safety of INT2104 intravenous infusion in adults with refractory/relapsing B cell malignancies. The study is a global, two-part, multicenter, open-label, single dose design with a dose escalation portion designed to inform the dose of INT2104 to be used in the dose confirmation part of the trial and future studies. INVISE has been granted Human Research Ethics Committee (HREC) approval and Clinical Trial Notification (CTN) clearance by the Australian Therapeutic Goods Administration (TGA) and Paul Ehrlich Institute (PEI) regulatory clearance in Germany. Additional information and enrollment criteria may be found on clinicaltrials.gov (NCT06539338).

About INT2104
INT2104 is a wholly-owned investigational gene therapy candidate, which specifically targets CD7-positive T and NK cells and delivers a CAR transgene to create effector CAR-T and CAR-NK cells in vivo. The CAR cells target CD20-positive B cells for the treatment of B cell malignancies. Unlike ex vivo CAR-T therapies, INT2104 is an off-the-shelf, single dose treatment, administered systemically through intravenous infusion without the need for lymphodepletion or for any special equipment or training.

On January 7, 2025 Immuneering Corporation (Nasdaq: IMRX), a clinical-stage oncology company seeking to develop and commercialize more effective and better tolerated therapies for cancer patients, reported a positive data update from three pancreatic cancer arms of its ongoing Phase 2a trial of lead program IMM-1-104, as well as plans to expand the Phase 2a trial to include three additional combination arms (Press release, Immuneering, JAN 7, 2025, View Source [SID1234649467]). While approved MEK inhibitors mainly benefit a subset of patients with BRAF-driven tumors, IMM-1-104 was designed to improve tolerability and expand indications to include RAS-mutated tumors such as those found in most pancreatic cancers.

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"We are excited to report an updated ORR of 43% and DCR of 86% for IMM-1-104 in combination with modified gemcitabine/nab-paclitaxel in first-line pancreatic cancer patients. For reference, the benchmark reported for gemcitabine/nab-paclitaxel in this setting had an ORR of 23% and DCR of 48%. We look forward to reporting further data in the second quarter of 2025 and have started planning for a potential pivotal clinical trial," said Ben Zeskind, Ph.D., CEO of Immuneering.

Dr. Zeskind continued: "Today we are also sharing initial data from IMM-1-104 in combination with modified FOLFIRINOX in first-line pancreatic cancer patients. We observed target lesion shrinkage across all evaluable patients, including a 100% reduction, a rare event in this patient population. Additionally, we are reporting initial data from our monotherapy arm of IMM-1-104 in second-line pancreatic cancer. We saw clear activity, including a partial response with a 67% target lesion reduction. We believe these results provide substantiating evidence of IMM-1-104’s contribution in combination with current therapies."

Dr. Zeskind concluded: "Importantly, we continue to observe a highly differentiated safety profile for IMM-1-104, which we designed to be better tolerated and more active than existing approved MEK inhibitors already driving annual net sales of ~$2.4 billion in 2023. Accordingly, we plan to add three new Phase 2a combination arms: IMM-1-104 with a BRAF inhibitor in BRAF-mutant melanoma, and IMM-1-104 with an immune checkpoint inhibitor in both melanoma and NSCLC. We expect to initiate these arms in 2025. Today we are setting a path to break new ground in indications where no MEK inhibitors have been approved, including pancreatic cancer, and aim to provide a better tolerated and more effective alternative where MEK inhibitors are already helping patients."

Updated Data from Phase 2a Arm Evaluating IMM-1-104 with Modified Gemcitabine/nab-Paclitaxel in First Line Pancreatic Cancer as of December 5, 2024

As of December 5, 2024, three patients in the Phase 2a arm evaluating IMM-1-104 with modified gemcitabine/nab-paclitaxel in first-line pancreatic cancer achieved complete or partial responses for an overall response rate of 43% (3/7) and disease control rate of 86% (6/7). Four patients remain on treatment.
Benchmarks for gemcitabine/nab-paclitaxel alone in first-line pancreatic cancer patients were established by the Phase 3 MPACT study, which included 1 Complete Response (CR) out of 431 patients, a 23% Overall Response Rate, and a 48% Disease Control Rate1. Benchmarks for modified (m) Gemcitabine/nab-Paclitaxel, the less intensive regimen utilized in the IMM-1-104 Phase 2 combination arm, include an 18.6% ORR2.
A favorable tolerability profile was observed for IMM-1-104 in combination with modified Gemcitabine/nab-Paclitaxel.
[1] Von Hoff, et al. N Engl J Med 2013;369:1691-1703, [2] Ahn DH, et al. Therapeutic Advances in Medical Oncology. 2017;9(2):75-82

"Immuneering’s Phase 2a data in first-line pancreatic cancer are very promising," said Tanios Bekaii-Saab, M.D., Leader of the Gastrointestinal Cancer Disease Group for the Mayo Clinic Cancer Center enterprise-wide and Medical Oncology consultant in Mayo Clinic in Phoenix, Arizona. "If current trends continue, the combination of IMM-1-104 with modified gemcitabine/nab-paclitaxel may provide improved efficacy and tolerability versus gemcitabine/nab-paclitaxel in the first-line pancreatic cancer setting, where patients continue to urgently need better options. In addition, having a MEK inhibitor that appears to be as well-tolerated as IMM-1-104 may provide new opportunities for patients with different types of cancer."

Initial Data from Phase 2a Arm Evaluating IMM-1-104 with Modified FOLFIRINOX in First Line Pancreatic Cancer as of December 5, 2024

As of December 5, 2024, all evaluable patients (n=4) experienced target tumor shrinkage and disease control, with one patient achieving a 100% reduction (PR).
The combination of IMM-1-104 plus modified FOLFIRINOX (mFFX) was observed to be generally well tolerated.
The Company is currently evaluating the 320 mg QD dose of IMM-1-104 in combination with modified FOLFIRINOX.
Initial Data from Phase 2a Arm Evaluating IMM-1-104 Monotherapy in Second Line Pancreatic Cancer as of December 5, 2024

"Having demonstrated compelling activity in both the combination and monotherapy settings for pancreatic cancer, the emerging tolerability profile for IMM-1-104 is also highly promising," said Brett Hall, Ph.D., Chief Scientific Officer, Immuneering Corporation. "Looking at the table of treatment-related adverse events observed in greater than 10% of patients in our monotherapy arm, no Grade 3 or Grade 4 events were observed, and only a handful of Grade 2 events were observed. The maturing safety profile for IMM-1-104 gives us confidence that Immuneering may have developed a better tolerated MEK-inhibitor, with exciting potential for vertical, immune-modifying, and orthogonal combinations. We expect to share expanded development plans for IMM-1-104 beyond pancreatic cancer, as we continue to explore options with investigators and third parties."

As of December 5, 2024, eleven of the twenty-one evaluable patients treated in the Phase 2a arm assessing IMM-1-104 as monotherapy in second-line pancreatic cancer achieved disease control, including one patient with 67% target lesion shrinkage (PR). Nine patients remain on treatment.
IMM-1-104 monotherapy was observed to be very well tolerated in second-line pancreatic cancer patients, suggesting that IMM-1-104 may be highly suitable for both monotherapy and combination therapy.
Immuneering previously announced that IMM-1-104 received Fast Track designation from the FDA for the treatment of first- and second-line pancreatic cancer, along with orphan drug designation. The FDA also recently granted Fast Track designation for IMM-1-104 as a treatment for patients with unresectable or metastatic NRAS-mutant melanoma who have progressed on or are intolerant to PD-1/PD-L1 based immune checkpoint inhibitors. Today’s data update follows initial data that was presented in September 2024 on the trial’s arm studying IMM-1-104 in combination with modified gemcitabine/nab-paclitaxel in first-line pancreatic cancer.

Today, Immuneering also announced initial pharmacokinetic, pharmacodynamic and safety data from the Phase 1 portion of the company’s Phase 1/2a trial of IMM-6-415. To date, IMM-6-415 has demonstrated its potential to induce Deep Cyclic Inhibition, and in doing so has been well tolerated – consistent with what was observed preclinically for the development candidate.

Near-Term Milestone Expectations

IMM-1-104

Further IMM-1-104 Phase 2a data expected in the second quarter of 2025
Initiation of Phase 2a arm of IMM-1-104 in combination with BRAF inhibitor in melanoma planned for 2025
Initiation of Phase 2a arms of IMM-1-104 in combination with checkpoint inhibitors in both melanoma and NSCLC planned for 2025
Conference Call

Immuneering will host a conference call and live webcast at 8:30 a.m. ET / 5:30 a.m. PT on January 7, 2025, to discuss the data and provide a business update. Individuals interested in listening to the live conference call may do so by dialing (800) 715-9871 for U.S callers and (646) 307-1963 for other locations and reference conference ID 4497245, or from the webcast link in the "investors" section of the company’s website at www.immuneering.com A webcast replay will be available in the investor relations section on the company’s website for 90 days following the completion of the call.

On January 7, 2025 GSK plc (LSE/NYSE: GSK) reported that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for GSK5764227 (GSK’227), its B7-H3-targeted antibody-drug conjugate (ADC) being evaluated for the treatment of adult patients with relapsed or refractory osteosarcoma (bone cancer) who have progressed on at least two prior lines of therapy (Press release, GlaxoSmithKline, JAN 7, 2025, View Source [SID1234649466]). The Breakthrough Therapy Designation aims to expedite the development and review of drugs with the potential to treat a serious condition and where preliminary clinical evidence may indicate substantial improvement over currently available therapy.1 This is the third regulatory designation for GSK’227, following the European Medicines Agency’s decision to grant Priority Medicines (PRIME) designation and the FDA’s decision to grant Breakthrough Therapy Designation for relapsed or refractory extensive-stage small-cell lung cancer in August 2024 and December 2024, respectively.2,3

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Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: "This latest regulatory designation for GSK’227 exemplifies the potential of our targeted ADC in patients with difficult to treat cancers. For patients with relapsed or refractory osteosarcoma, there is an urgent unmet medical need with no approved treatment options once the cancer returns a second time, and chemotherapy provides limited benefit in this setting."

The US FDA’s Breakthrough Therapy Designation is supported by data from the ARTEMIS-002 study. This is a phase II, open-label, randomised, multi-centre, clinical trial evaluating the efficacy and safety of GSK’227 in patients with relapsed or refractory osteosarcoma and other unresectable bone and soft tissue sarcomas, conducted by Hansoh Pharma. More than 60 patients were enrolled, including 42 patients with osteosarcoma. Results from ARTEMIS-002 were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.4 Last year, GSK acquired exclusive worldwide rights (excluding China’s mainland, Hong Kong, Macau, and Taiwan) from Hansoh Pharma to progress clinical development and commercialisation of GSK’227. GSK recently began a global phase I trial (NCT06551142) as a part of the development plan to support a registrational pathway for GSK’227.

Osteosarcoma mainly affects children and young adults and is the most common primary bone cancer, accounting for 20-40% of all bone cancers.5 It is a rare disease with an annual incidence of 3.3 patients per million in the US, representing less than 1% of all new cancer diagnoses.6,7 Approximately 20-30% of patients who present with localised (non-metastatic) osteosarcoma and 80% of those who present with metastatic osteosarcoma experience relapsed or refractory disease.8 Following first-line chemotherapy, treatment options for patients with relapsed or refractory osteosarcoma are severely limited, with no clear standard of care available.9 After patients progress on two prior lines of treatment, options become even more limited, with no approved therapies.

About GSK’227
GSK’227, also known as HS-20093, is a novel investigational B7-H3-targeted antibody-drug conjugate composed of a fully human anti-B7-H3 monoclonal antibody covalently linked to a topoisomerase inhibitor payload. HS-20093 is being developed by Hansoh Pharma for the treatment of lung cancer, sarcoma, head and neck cancers and other solid tumours in multiple phase I, II and III clinical trials in China. GSK’s global phase I trial for GSK’227 began in August 2024.