On June 27, 2024 EditCo Bio, Inc., a leader in genome engineering innovation, reported the expansion of its T-cell editing portfolio with the launch of Knockout CD8+ T-cell Pools (Press release, EditCo Bio, JUN 27, 2024, View Source [SID1234644588]). This new addition builds upon the success of their Knockout CD4+ T-cell Pools, offering researchers an advanced tool for primary T-cell editing that brings unprecedented precision and scalability to cancer and immunotherapy research.

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Leveraging EditCo Bio’s cutting-edge automated platform, the new Knockout CD8+ T-cell Pools allow researchers to bypass challenging optimization steps and access highly functional edited T-cells ready for immediate use. This innovation accelerates the transition from research discovery to clinical application and delivers several key benefits:

Accelerated results: EditCo Bio’s unique 7-day protocol and proprietary guide RNA technology achieve knockout efficiencies approaching 100% in primary human CD8+ T-cells. Additionally, EditCo has several prescreened and optimized donor cells available to kick off projects immediately.
Dependable performance: Edited CD8+ T-cell pools demonstrate exceptional editing efficiency (~100%) and viability (>85%). with editing efficiency unchanged for at least 4 weeks in culture.
Enhanced functionality: Edited CD8+ T-cell pools showed antigen-specific CD107a mobilization, a hallmark of cytotoxic activity.
Customizable solutions: EditCo Bio can efficiently onboard customer-supplied donor cells, ensuring high knockout efficiencies, viability, and turn-around times tailored to specific project needs.
"For researchers working on the front lines of immunotherapy, having access to high-quality CD8+ T-cells can significantly accelerate the pace of discovery and therapeutic development," said Travis Maures, CSO of EditCo Bio. "Our new Knockout CD8+ T-cell Pools provide the precision, efficiency, and scalability needed to push the boundaries of what’s possible in cellular research."

The addition of Knockout CD8+ T-cell Pools further strengthens EditCo Bio’s comprehensive Engineered Cell portfolio, solidifying its position as a leader in cell engineering solutions. The company plans to continue to expand its range of edited primary cell products to include other primary cell subsets, which will be available later this year.

For more information regarding EditCo Bio’s Knockout T-cell Pools, visit www.EditCo.bio/contact.

On June 27, 2024 Abdera Therapeutics Inc., a biopharmaceutical company leveraging its advanced antibody engineering ROVEr platform to design and develop tunable, precision radiopharmaceuticals for cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ABD-147 for the treatment of patients with extensive stage small cell lung cancer (ES-SCLC) who have progressed on or after platinum-based chemotherapy (Press release, Abdera Therapeutics, JUN 27, 2024, View Source [SID1234644587]). ABD-147 is a next-generation precision radiopharmaceutical biologic therapy designed to deliver Actinium-225 (225Ac) to solid tumors expressing DLL3, a protein found on the surface of neuroendocrine tumors, but rarely expressed on the surface of normal cells or tissues.

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The FDA’s Fast Track program is designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Clinical programs with Fast Track designation may benefit from early and frequent communication with the FDA throughout the regulatory review process and may also be eligible for Accelerated Approval and Priority Review if relevant criteria are met.

"Aggressive neuroendocrine cancers such as SCLC carry a poor prognosis and new treatment options are urgently needed," said Lori Lyons-Williams, president and chief executive officer. "These cancers have the most aggressive clinical course of any type of pulmonary tumor and often rapidly metastasize to other parts of the body. We are thrilled the FDA has recognized the potential of ABD-147 to become a transformative treatment option for SCLC and we are excited to begin clinical development and provide ABD-147 to patients in need."

In the second half of 2024, Abdera plans to initiate a first-in-human Phase 1 clinical trial with ABD-147 in patients with SCLC or large cell neuroendocrine carcinoma (LCNEC) who previously received platinum-based therapy.

About Small Cell Lung Cancer and Large Cell Neuroendocrine Carcinoma

The global incidence for SCLC and LCNEC has been reported to represent approximately 325,000 patients and is expected to increase 4% annually through 2029. In the U.S., the incidence has been reported to be approximately 35,000 new cases annually. Fifteen percent of all lung cancer cases are high-grade neuroendocrine cancers. These cancers have the most aggressive clinical course of any type of pulmonary tumor and often metastasize to other parts of the body, including the brain, liver and bone. Without treatment, the median survival from diagnosis has been reported to be only two to four months. With treatment, the overall survival at five years is 5% to 10% for SCLC, and 15% to 25% for LCNEC. SCLC and LCNEC generally carry a poor prognosis and new treatment options are urgently needed.

About ABD-147

ABD-147 is a targeted radiopharmaceutical biologic therapy designed to deliver Actinium-225 (225Ac), a highly potent alpha-emitting radioisotope, to solid tumors expressing delta-like ligand 3 (DLL3) with high affinity. DLL3 is a protein in the Notch pathway that is critical for the development and regulation of neuroendocrine versus epithelial cell differentiation in the lungs. In certain high grade neuroendocrine carcinomas including small cell lung cancer (SCLC), DLL3 is upregulated and specifically expressed on the cell surface in more than 80% of cases. In contrast, DLL3 is absent or very rarely expressed on the surface of nonmalignant cells. Given the high specificity of DLL3 expression on cancer cells and the distinct mechanism of action, DLL3 represents a compelling target for treating SCLC and other DLL3+ solid tumors with targeted radiotherapy.

About the ROVEr Platform

Abdera’s Radio Optimized Vector Engineering (ROVEr) platform enables the company to custom-engineer targeted radiopharmaceuticals with tunable pharmacokinetic (PK) properties to achieve high tumor uptake while minimizing renal exposure and mitigating other systemic radiotoxicities such as myelosuppression. Abdera can optimize the delivery and therapeutic index of potent radioisotopes capable of emitting powerful alpha or beta particles to selectively destroy tumor cells while sparing healthy cells, providing patients with potentially transformative new cancer treatments.

Abdera’s approach offers the ability to design radiotherapeutics against virtually any cancer target expressed on the cell surface. Coupled with a highly potent mechanism of cell killing, the ROVEr platform is uniquely poised to exploit both high- and low-expressing targets to selectively deliver therapeutic levels of radioisotope to cancer cells.

On June 27, 2024 Abbisko Therapeutics Co., Ltd. (Abbisko Therapeutics) reported that it has presented new phase II clinical data of its highly selective FGFR4 inhibitor irpagratinib (ABSK011) in combination with atezolizumab for the treatment of advanced hepatocellular carcinoma（HCC）at the 2024 ESMO (Free ESMO Whitepaper)-GI Congress (Press release, Abbisko Therapeutics, JUN 27, 2024, View Source [SID1234644586]). The presentation highlights that 220mg BID of irpagratinib in combination with atezolizumab demonstrated promising antitumor activity with an objective response rate (ORR) of 50% in FGF19+ HCC patients.

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ESMO-GI, a world-renowned gastrointestinal oncology conference, is being held in Munich, Germany, from June 26 to 29, 2024.

Abbisko presentations at ESMO (Free ESMO Whitepaper)-GI 2024:

Title: A Phase 2 Study of Irpagratinib (ABSK-011) plus Atezolizumab in Patients with Advanced Hepatocellular Carcinoma (HCC)
Poster display number：171P
Poster display session: Hepatocellular and non-biliary liver cancer
Poster display date and time: 27 June 2024, 15:35-16:30 PM (UTC+1)

Summary:

At the 2024 ESMO (Free ESMO Whitepaper)-GI conference, Abbisko Therapeutics debuted new clinical trial results with the combination of irpagratinib and atezolizumab. In HCC patients with FGF19 overexpression, the objective response rate (ORR) was 50% (5/10)in the 220 mg BID cohort, demonstrating this novel combination therapy has notable benefits in enhancing the ORR. Notably, strong efficacy and good safety were also observed in patients who had previously received immune checkpoint inhibitor (ICI) therapy, providing further evidence that targeting FGF19-FGFR4 may provide a much-needed differentiated treatment option for HCC.

Given the encouraging preliminary results from this study, Abbisko plans to explore dual/triple combinations with irpagratinib in earlier lines of therapy for HCC. Abbisko continues to look forward to combination approaches with irpagratinib to better address HCC and bring hope to patients, with aims to conduct further research and innovation in this area.

Background:

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and ranks as the sixth most prevalent cancer and third leading cause of death worldwide. Dysregulation of FGF19-FGFR4 signaling accounts for approximately 30% of HCC and plays a pivotal role in driving HCC tumorigenesis. Irpagratinib is a highly potent and selective FGFR4 inhibitor, with potential to become a first-in-class or best-in-class FGFR4 inhibitor. Abbisko Therapeutics previously presented clinical data from its first-in-human study of irpagratinib at the 2023 ESMO (Free ESMO Whitepaper) Annual Meeting, demonstrating promising anti-tumor activity as a single agent with an ORR of 40.7% in FGF19 overexpressed late-line HCC patients.

To further explore the therapeutic potential of irpagratinib, Abbisko is conducting a phase 2 clinical trial of irpagratinib in combination with atezolizumab. This trial is investigating irpagratinib in combination with atezolizumab, a PD-L1 antibody, in FGF19+ advanced HCC patients, to understand safety and efficacy.

On June 27, 2024 Kazia Therapeutics Limited (NASDAQ: KZIA), a biotechnology company specialising in oncology, reported that the presentation of new data from its lead program, paxalisib, at the upcoming 21st International Symposium on Pediatric Neuro-Oncology (ISPNO 2024) June 29 – July 2, 2024, in Philadelphia, PA (Press release, Kazia Therapeutics, JUN 27, 2024, View Source [SID1234644585]). Kazia concurrently announces publication of an article in European Journal of Cancer highlighting the need for evaluating mutation-specific, CNS penetrant, inhibitors to treat pediatric patients with Diffuse Midline Glioma (DMG).

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There will be three paxalisib-related presentations in total at ISPNO, including data from the Phase 2 PNOC DMG-ACT (DMG-Adaptive Combination Trial, PNOC022) study evaluating the efficacy and safety of paxalisib in combination with ONC201. As a follow up to data presented last year at the Society for NeuroOncology, 28th Annual Meeting, lead researchers will discuss survival, pharmacokinetics, and tumor biomarkers from 132 diffuse midline glioma (DMG) patients enrolled in the Phase 2 study. Highlights of the abstract include median overall survival of 13.2 months in Cohort 1 (newly diagnosed, enrolled pre-radiation n=33), 15.8 months in Cohort 2 (newly diagnosed, enrolled post-radiation n=69) and 8.8 months in Cohort 3 (relapsed patients, enrolled after progression n=30).

The second presentation is based on novel preclinical data utilizing the addition of a novel HDAC inhibitor to the backbone therapy of paxalisib in DMG models. The third presentation will highlight preclinical data results of the combination therapy of paxalisib and gemcitabine for patients with relapsed/recurrent atypical teratoid/rhabdoid tumors AT/RT by Johns Hopkins University researchers. Based on these findings, the Pacific Pediatric Neuro-Oncology Consortium is planning to include this combination therapy in its next AT/RT international clinical trial.

Summary of Abstracts (View Source;date=%222024-6-30%22)
Clinical Trials; July 2, 2024; 8:15am
TRLS-14: PNOC022 report: a combination therapy trial using an adaptive platform design for patients with diffuse midline glioma at initial diagnosis, post-radiation therapy, or progression
Cassie Kline, Andrea Franson, Anuradha Banerjee, Alyssa T Reddy, et al

Poster Session I; June 30, 2024; 5pm
ATRT-15 Combining the PI3K inhibitor paxalisib with nucleoside analog gemcitabine to improve survival of atypical teratoid/rhabdoid tumors
Tyler Findlay, Kristen Malebranche, Anupa Geethadevi, Charles Eberhart, Jeffrey Rubens, Eric Raabe

DIPG-21 Preclinical assessment of a multimodal treatment approach with Givinostat, Paxalisib, and radiotherapy for Diffuse Midline Glioma (DMG)
Aimée du Chatinier, Michaël H Meel, Piotr Waranecki, Dennis S Metselaar, Esther

The European Journal of Cancer publication titled Paediatric Strategy Forum for Medicinal Product Development of PI3-K, mTOR, AKT and GSK3β Inhibitors in Children and Adolescents with Cancer is the output from a two-day forum in April 2023 at Dana Farber Cancer Institute. Consisting of patient advocates, regulators, researchers and pediatric clinicians, the publication concludes "Evaluation of mutation-specific, CNS-penetrant PI3-K inhibitors in children with DMG should be prioritised and innovative regulatory approaches are needed in view of the rarity of the population." The paper can be accessed at the following website: View Source(24)00801-3/fulltext

On June 27, 2024 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported plans to expand its ongoing Phase 1 clinical trial to include two combination cohorts evaluating EO-3021 for the treatment of advanced gastric or gastroesophageal junction cancer (Press release, Elevation Oncology, JUN 27, 2024, View Source [SID1234644584]). Following recently signed clinical supply agreements with Eli Lilly and Company (Lilly) and GSK, respectively, Elevation Oncology will evaluate EO-3021 in combination with ramucirumab, a VEGFR2 inhibitor, in second-line patients and in combination with dostarlimab, a PD-1 inhibitor, in the front-line setting. The Company expects to initiate dosing in the combination portion of the Phase 1 trial by year-end 2024.

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"EO-3021 has the potential to change the treatment paradigm for tumors that express Claudin 18.2, including a majority of gastric and gastroesophageal junction adenocarcinomas," said Valerie Malyvanh Jansen, M.D., Ph.D., Chief Medical Officer of Elevation Oncology. "Based on safety data from preclinical and clinical trials, we believe EO-3021 benefits from a differentiated safety profile and will be readily combinable. We also know that combination-based regimens are a mainstay of cancer care, and that the combination of two therapies with distinct mechanisms of action often enables patients to achieve deeper, more durable responses. As such, we are excited to begin evaluating EO-3021 together with ramucirumab, a VEGFR2 inhibitor, and with dostarlimab, a PD-1 inhibitor, in the second- and first-line settings, respectively. In parallel, we continue to advance our Phase 1 trial of EO-3021 monotherapy toward initial safety and efficacy data by mid-third quarter."

Clinical Development Plans for EO-3021 in Combination

EO-3021 is a differentiated, potential best-in-class antibody drug conjugate (ADC) targeting Claudin 18.2. EO-3021 was designed with site-specific conjugation at glutamine (Q295), with the goal of increasing the stability of the linker-payload and minimizing the potential for free monomethyl auristatin E (MMAE) compared to traditional cysteine-based conjugation. In preclinical studies and the Phase 1 clinical trial conducted by Elevation Oncology’s partner, data showed a favorable tolerability profile, with limited MMAE-related toxicities.

Initial development of EO-3021 in combination will explore two regimens for the treatment of gastric or gastroesophageal junction cancer:

EO-3021 in combination with ramucirumab in second-line patients: Ramucirumab is a monoclonal antibody that targets VEGFR2 and is approved for use in combination with paclitaxel for the treatment of second-line gastric or gastroesophageal junction cancer with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy. With EO-3021, Elevation Oncology aims to introduce a combination agent that, when paired with ramucirumab, can potentially deliver improved safety and efficacy as compared to the approved combination of ramucirumab and paclitaxel.
EO-3021 in combination with dostarlimab in front-line patients: Dostarlimab is approved alone and in combination with chemotherapy for certain types of dMMR and MSI-H endometrial cancer in the US; it also has an accelerated approval in certain dMMR solid tumors. By combining EO-3021 and an immune checkpoint inhibitor, Elevation Oncology aims to deliver synergistic benefit, potentially offering patients improved outcomes beyond those seen with existing immunotherapy regimens for gastric or gastroesophageal junction cancer in the front-line setting.
Each combination cohort will include a dose escalation and expansion portion, evaluating the combination of EO-3021 and ramucirumab or EO-3021 and dostarlimab. The primary endpoints will include safety and anti-tumor activity. Elevation Oncology plans to initiate dosing in the combination portion of the Phase 1 trial by year-end 2024.

In June 2024, Elevation Oncology entered into clinical supply agreements with Lilly and GSK to supply their respective compounds for these combination cohorts. Elevation Oncology will sponsor and conduct all clinical development of both combinations and will assume all costs associated with the study. All companies will retain commercial rights to their respective compounds.

Elevation Oncology continues to enroll patients in the monotherapy cohort of its ongoing Phase 1 clinical trial (NCT05980416) and remains on track to share initial safety and efficacy data by mid-third quarter 2024, with additional data in the first half of 2025.

About EO-3021

EO-3021 (also known as SYSA1801) is a differentiated, clinical-stage antibody drug conjugate (ADC) with best-in-class potential comprised of an immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets Claudin 18.2. EO-3021 is site-specifically conjugated to the monomethyl auristatin E (MMAE) payload via a cleavable linker with a drug-to-antibody ratio (DAR) of 2. Claudin 18.2 is a specific isoform of Claudin 18 that is normally expressed in gastric epithelial cells. During malignant transformation, the tight junctions may become disrupted, exposing Claudin 18.2 and allowing them to be accessible by Claudin 18.2 targeting agents. Elevation Oncology is evaluating EO-3021 in a Phase 1 study (NCT05980416) in patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2 including gastric, gastroesophageal junction, pancreatic or esophageal cancers.

Elevation Oncology has the exclusive rights to develop and commercialize EO-3021 in all global territories outside Greater China.