On November 25, 2024 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company developing a novel class of therapeutic biologics to selectively engage and modulate disease-specific T cells for the treatment of cancer and autoimmune disease, reported that it will take part in an unplugged fireside discussion at the Piper Sandler 36th Annual Healthcare Conference being held in New York, NY, Dec 3-5, 2024 (Press release, Cue Biopharma, NOV 25, 2024, View Source [SID1234648624]).

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During the fireside discussion, Cue Biopharma will provide an overview highlighting recent clinical and preclinical program updates as well as strategic business and partnering model objectives.

Presentation Details
Date and Time: Wednesday, December 4, 2024, from 9 a.m. EST – 9:25 a.m. EST
Webcast Link: View Source;tp_key=a82c532edc
Presenter: Daniel Passeri, M.Sc., J.D., chief executive officer, Cue Biopharma

A live and archived webcast of the fireside discussion will be available on the Events page in the Investors and Media section of the Company’s website at www.cuebiopharma.com. The webcast will be archived for 30 days.

On November 25, 2024 D3 Bio, a global clinical stage biotechnology company focusing on discovery, development, and registration of innovative cancer drugs, reported that its lead compound, a next-generation KRAS G12C inhibitor, D3S-001, demonstrated rapid target engagement, overcame the limiting factors of nucleotide cycling and RTK activation, and showed robust preclinical and clinical activities in KRAS G12C-mediated cancers, in a study published in Cancer Discovery (Press release, D3 Bio, NOV 25, 2024, View Source [SID1234648641]).

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In a paper titled, "A KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities", researchers from D3 Bio and its collaborators demonstrated that D3S-001 performed significantly better than other KRAS G12C inhibitors in multiple pre-clinical and clinical studies designed to profile the class of KRAS G12C small molecule inhibitors. Specifically, D3S-001 demonstrated substantially improved covalent potency and better and faster target engagement (TE) kinetics, compared to the approved drugs (sotorasib and adagrasib) in the class. This suggests that D3S-001 has the potential to "lock" KRAS G12C in its inactive (GDP-bound) state more efficiently, possibly resulting in cellular active KRAS depletion in clinically relevant doses. In addition, D3S-001’s high potency and rapid kinetics allow it to block the GDP-to-GTP transition even in the presence of growth factors. In contrast, first-generation G12C inhibitors are less effective in these conditions, which may contribute to their limited clinical efficacy.

In cell line and patient-derived tumor xenograft models across multiple cancer types, D3S-001 demonstrated significantly more robust anti-tumor responses than the other KRAS G12C inhibitors in the study. Importantly, these include a delay in disease progression in tumors that were resistant to an FDA-approved KRAS G12C inhibitor. D3S-001 also exhibited brain penetration properties, resulting in durable intracranial tumor regression in mouse models with brain metastases.

Citing the ongoing D3S-001 Phase 1/2 trial in KRAS G12C-mediated solid tumors, the study noted that durable RECIST responses were observed across all dose cohorts, as well as systemic and intracranial anti-tumor activity in two highlighted patients with non-small cell lung cancer (NSCLC) enrolled in the first dose cohort of this trial.

The researchers conclude that D3S-001 is a next-generation GDP-bound KRAS G12C inhibitor with robust antitumor preclinical activity and promising durable responses in the ongoing clinical trial, which could overcome the limitations of the first-generation drugs.

Separately, in an oral presentation at the ESMO (Free ESMO Whitepaper) Congress 2024, dose-escalation data from the D3S-001 Phase 1 clinical trial in 42 patients of locally advanced or metastatic KRAS G12C-mutated cancers with prior systemic treatments was presented. The presenter and trial investigator, Byoung Chul Cho, MD, PhD, Professor in the Division of Medical Oncology at Yonsei Cancer Center, Yonsei University College of Medicine and Chief of Lung Cancer Center at Yonsei Cancer Center, Yonsei University College of Medicine, highlighted that D3S-001 functionally abolishes the KRAS G12C transition from GDP-bound (inactive) state to the GTP-bound (active) state, depleting cellular active KRAS, even in the presence of growth factor stimulation. Results from the Phase 1a dose-escalation study (42 patients in total) showed favorable tolerability across different dose levels, with no maximum-tolerated dose reached. In addition, D3S-001 demonstrated consistent and promising efficacy in the G12C-inhibitor naïve population, with a confirmed overall response rate (ORR) of 73.5% across tumor types. Researchers also observed brain tumor shrinkage in patients with brain metastases and a rapid, sustained reduction of mutant allele frequency (MAF), which measures mutated genes, in circulating tumor cell DNA (ctDNA) as early as Day 8 post-treatment. Expansion study cohorts are ongoing and focus on monotherapy and combination therapy regimens in non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC).

"While promising, the first generation of KRAS G12C inhibitor class has exhibited limited durability in the clinic, which could be addressed by a more efficient mode of action," said Dr. Cho. "This paper, demonstrating that D3S-001 has a more robust covalent potency and rapid target engagement kinetics, unaffected by RTK activation, unveils a novel mode of action that correlates with pre-clinical anti-tumor activity and promising Phase 1 clinical results. Furthermore, the study shows, for the first time, that GDP-bound KRAS G12C inhibitors can deplete cellular-active KRAS as efficiently the GTP-bound inhibitor class, suggesting that D3S-001 could address the issues that have challenged this class of drugs."

"Believing that a next-generation KRAS-G12C inhibitor with significantly improved target inhibition efficiency could become the backbone of a new standard of care for cancers carrying KRAS G12C mutations and provide profound clinical advantages, we selected D3S-001 for its superior covalent potency and differentiated target engagement kinetics," said George Chen, MD, Founder, Chairman and CEO, D3 Bio. "This study validates our strategy of discovering a next-generation and differentiated G12C inhibitor with rapid target engagement to deliver more efficacious clinical activity. At the ESMO (Free ESMO Whitepaper) 2024 Congress, we presented Phase 1 data from 42 patients, showing a consistent and clinically meaningful response across all cancer types. We are excited with the progress of D3S-001, a potential best-in-class compound, and expect to report topline Phase 2 data in 2025."

About D3S-001

D3S-001 is a next-generation KRAS G12C inhibitor designed to enhance KRAS G12C target engagement. In preclinical investigations, D3S-001 has demonstrated high covalent potency, the ability to rapidly and completely engage the KRAS G12C target at clinically relevant doses and CNS penetration properties. D3S-001 is currently in a Phase 2 global clinical trial in patients with advanced solid tumors harboring a KRAS G12C mutation, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and other tumor types. For detailed information about D3S-001, please refer to the highlighted Research Article published at the 2024 September issue of Cancer Discovery, titled "D3S-001, A KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities" (Cancer Discovery 1 September 2024; 14 (9): 1675–1698. View Source). D3S-001 has received US FDA Orphan Drug Designation (ODD) for the treatment of pancreatic cancer and Fast Track Designation (FTD) for the treatment of late-line non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).

For more on the D3S-001 clinical trial, please go to: View Source;rank=1

On November 25, 2024 Immix Biopharma, Inc. ("ImmixBio", "Company", "We" or "Us" or "IMMX"), a clinical-stage biopharmaceutical company developing cell therapies for AL Amyloidosis and select immune-mediated diseases, reported that additional NEXICART-1 NXC-201 clinical data in relapsed/refractory AL Amyloidosis has been selected for oral presentation at the upcoming 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting to be held in San Diego, California, December 7-10, 2024 (Press release, Immix Biopharma, NOV 25, 2024, View Source [SID1234648609]).

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"NXC-201 is the only CAR-T in development for relapsed/refractory AL amyloidosis patients," said Ilya Rachman, MD PhD, Chief Executive Officer of Immix Biopharma. "NXC-201 continues to demonstrate promising results in this underserved patient population." Gabriel Morris, Chief Financial Officer of Immix Biopharma, added, "We are pleased to continue to demonstrate our focus and leadership in relapsed/refractory AL Amyloidosis at the upcoming 66th annual ASH (Free ASH Whitepaper) meeting in San Diego."

ASH Presentation Details (CAR-T NXC-201 in relapsed/refractory AL Amyloidosis)

Event 66th ASH (Free ASH Whitepaper) Annual Meeting and Exposition, San Diego, CA
Title "Efficacy and Safety of Anti-BCMA Chimeric Antigen Receptor T-Cell (CART) for the Treatment of Relapsed and Refractory AL Amyloidosis"
Presentation
Date/Time (Pacific Time)
Publication #894
Session Date: Monday, December 9, 2024
Session Name: 652. MGUS, Amyloidosis, and Other Non-Myeloma Plasma Cell Dyscrasias: Clinical and Epidemiological: Ignored no Longer-Progress in AL Amyloidosis
Session Time: 2:45 PM-4:15 PM
Presentation Time: 4:00PM PT
About NEXICART-1
NEXICART-1 (NCT04720313) is an open-label, ex-U.S. Phase 1b/2 clinical trial of NXC-201 (formerly HBI0101) in patients with relapsed/refractory multiple myeloma and relapsed/refractory AL amyloidosis (including AL Amyloidosis patients with impaired cardiac function and including AL Amyloidosis patients exposed to prior BCMA-targeted therapy). The primary objective of the study is to characterize the safety and efficacy of NXC-201. NEXICART-1 clinical results are available at View Source .

About NEXICART-2
NEXICART-2 (NCT06097832) is an open-label, single-arm, multi-site U.S. Phase 1b/2 dose expansion clinical trial of CAR-T NXC-201 in relapsed/refractory AL Amyloidosis. NEXICART-2 is expected to enroll 40 patients with adequate cardiac function who have not been exposed to prior BCMA-targeted therapy. The study is designed with a standard 6 patient safety-run in to evaluate two doses (three patients each at 150 million CAR+T cells and 450 million CAR+T cells) (both dose levels were evaluated in the NEXICART-1 study and have produced complete responses in relapsed/refractory AL Amyloidosis patients). The study aims to evaluate the safety and efficacy of NXC-201. Primary endpoints are complete response rate and overall response rate, according to consensus recommendations (Palladini et al. 2012).

About NXC-201
NXC-201 is a sterically-optimized BCMA-targeted chimeric antigen receptor T (CAR-T) cell therapy. Initial data from Phase 1b/2 ex-U.S. study NEXICART-1 has demonstrated no neurotoxicity of any kind in AL Amyloidosis.

NXC-201 is being studied in a comprehensive clinical development program for the treatment of patients with relapsed/refractory AL amyloidosis, with the potential to expand into select immune-mediated diseases. The NXC-201 NEXICART-2 (NCT06097832) U.S. clinical trial builds on a robust clinical dataset. NXC-201 has been awarded Orphan Drug Designation (ODD) in AL Amyloidosis by the US FDA and in the EU by the EMA.

About AL Amyloidosis
AL amyloidosis is caused by abnormal plasma cells in the bone marrow, which produce misfolded amyloid proteins that build-up in the heart, kidney, liver, and other organs. This build-up causes progressive and widespread damage to multiple organs, including heart failure, and leads to high mortality rates.

The U.S. observed prevalence of relapsed/refractory AL Amyloidosis is estimated to be growing at 12% per year according to Staron, et al Blood Cancer Journal, to approximately 33,277 patients in 2024.

The Amyloidosis market was $3.6 billion in 2017, and is expected to reach $6 billion in 2025, according to Grand View Research.

On November 25, 2024 Novartis reported that it will present data from more than 65 abstracts, including investigator-initiated trials at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition and the 2024 San Antonio Breast Cancer Symposium (SABCS) (Press release, Novartis, NOV 25, 2024, View Source [SID1234648625]).

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"By prioritizing research in areas of greatest medical need and focusing on earlier stages of disease, we aim to change the treatment paradigm for people who require additional treatment options," said Jeff Legos, Executive Vice President, Global Head of Oncology Development, Novartis. "The new data being presented at ASH (Free ASH Whitepaper) and SABCS underscore our commitment to patients with cancer or blood disorders and follow new, expanded indications for Scemblix and Kisqali along with recent updates in national treatment guidelines."

In addition to late-breaking data, Novartis will host an art gallery-style exhibit at SABCS featuring personal letters and stories written by people impacted by breast cancer, sharing their raw, authentic perspectives on aspects of the breast cancer journey. These letters and stories aim to uplift patients, encourage reflection, and demonstrate strength and unity among the breast cancer community.

Key abstracts accepted by ASH (Free ASH Whitepaper) include:

Medicine or Disease State      Abstract Title      Abstract Number/ Presentation Details      
Scemblix Asciminib (ASC) Demonstrates Favorable Safety and Tolerability Compared with Each Investigator-Selected Tyrosine Kinase Inhibitor (IS TKI) in Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) in the Pivotal Phase 3 ASC4FIRST Study

Abstract #475
Oral Presentation
Sunday, December 8
9:30 – 11:00 AM PT
Scemblix    Efficacy and Safety of Asciminib in Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Interim Results from the Phase 2 ASC2ESCALATE Trial in the Cohort of Patients (Pts) after 1 Prior Tyrosine Kinase Inhibitor (TKI)

Abstract #479
Oral Presentation
Sunday, December 8
9:30 – 11:00 AM PT
Scemblix Asciminib Shows High Efficacy and Favorable Tolerability at 80 Mg Once Daily and 40 Mg Twice Daily in Patients with Chronic Phase Chronic Myelogenous Leukemia Previously Treated with 2 or More Tyrosine Kinase Inhibitors: Primary Analysis from the ASC4OPT Study

Abstract #4526
Poster Presentation
Monday, December 9
6:00 – 8:00 PM PT
Scemblix Treatment with Asciminib as a Second Line after One Prior Tyrosine Kinase Inhibitor (TKI) in Patients with Chronic-Phase Chronic Myeloid Leukemia (CML-CP)– a Chart Review Study in the United States

Abstract #3812
Poster Presentation
Sunday, December 8
6:00 – 8:00 PM PT
Ianalumab (VAY736) A Phase 2 Study of Ianalumab in Patients with Primary Immune Thrombocytopenia Previously Treated with at Least Two Lines of Therapy: Interim Results from VAYHIT3

Abstract #710
Oral Presentation
Monday, December 9
10:30 AM – 12:00 PM PT
Rapcabtagene autoleucel (YTB323) Rapcabtagene Autoleucel (YTB323) in Patients (Pts) with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL): Phase II Trial Clinical Update

Abstract #67
Oral Presentation
Saturday, December 7
9:30 – 11:00 AM PT
Fabhalta Oral Iptacopan Monotherapy Leads to Long-Term Improvements in Patient (Pt)-Reported Health-Related Quality of Life (HRQoL) and Investigator-Assessed Signs and Symptoms of Paroxysmal Nocturnal Hemoglobinuria (PNH): 48-Week (Wk) Results from the Phase III APPLY-PNH and APPOINT-PNH Trials

Abstract #4079
Poster Presentation
Monday, December 9
6:00 – 8:00 PM PT
Fabhalta The Effect of Oral Iptacopan Monotherapy on Hematological Parameters in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Is Consistent Regardless of the Type of Prior Anti-C5 Treatment Received: A Post Hoc Analysis of 24-Week Data from the Randomized Phase III APPLY-PNH Trial

Abstract #4087
Poster Presentation
Monday, December 9
6:00 – 8:00 PM PT
Fabhalta Baseline Characteristics of Individuals with Paroxysmal Nocturnal Hemoglobinuria in an App-Based Home-Reported Outcomes Study to Evaluate Disease Burden

Abstract #2327
Poster Presentation
Saturday, December 7
5:30 – 7:30 PM PT
Pelabresib (CPI-0610) Updated Results from the Phase 3 Manifest-2 Study of Pelabresib in Combination with Ruxolitinib for Janus Kinase Inhibitor–Naïve Patients with Myelofibrosis Abstract #3178
Poster Presentation
Sunday, December 8
6:00 PM – 8:00 PM PT
Key abstracts accepted by SABCS include:

Medicine or Disease State      Abstract Title      Abstract Number/ Presentation Details      
Kisqali (ribociclib)* Distant disease-free survival (DDFS) across key subgroups from the phase 3 NATALEE trial of ribociclib (RIB) plus a nonsteroidal aromatase inhibitor (NSAI) in patients with HR+/HER2- early breast cancer (EBC)

Abstract #P4-09-22
Poster Session
Thursday, December 12
5:30 – 7:30 PM CST

Kisqali      Impact of ribociclib dose reduction on efficacy in patients with hormone receptor– positive/human epidermal growth factor receptor 2–negative (HR+/HER2-) early breast cancer (EBC) in NATALEE

Abstract #P1-11-16
Poster Session
Wednesday, December 11
12:30 – 2:00 PM CST
Kisqali Risk of recurrence in real-world (RW) NATALEE- and monarchE-eligible populations of patients with HR+/HER2- early breast cancer (EBC) in an electronic health record (EHR)-derived database

Abstract #P2-12-02
Poster Session
Wednesday, December 11
5:30 – 7:00 PM CST

Kisqali Tolerability of First-Line (1L) Treatment (tx) With Ribociclib (RIB) for Metastatic Breast Cancer (MBC) Using 2 Large US Data Sources

Abstract #P3-10-14
Poster Session
Thursday, December 12
12:30 – 2:00 PM CST

Kisqali Impact of body mass index (BMI) on the safety and efficacy of ribociclib (RIB) in patients (pts) with HR+/HER2- advanced breast cancer (ABC): pooled analysis of the MONALEESA (ML)-2, -3, and -7 trials

Abstract #P2-09-20
Poster Session
Wednesday, December 11
5:30 – 7:00 PM CST

Kisqali First-line (1L) ribociclib (RIB) + endocrine therapy (ET) vs combination chemotherapy (combo CT) in clinically aggressive HR+/HER2- advanced breast cancer (ABC): a subgroup analysis of RIGHT Choice by intrinsic subtype & gene & signature expression

Abstract #PS2-06
Poster Presentation
Thursday, December 12
7:00 – 8:30 AM CST

Product Information    
For full prescribing information, including approved indications and important safety information about marketed products, please visit View Source

On November 25, 2024 Shorla Oncology (‘Shorla’), a U.S.-Ireland specialty pharmaceutical company, reported that the FDA has approved IMKELDI (imatinib) oral solution, the first oral liquid form of imatinib to treat certain forms of leukemia and other cancers (Press release, Shorla Oncology, NOV 25, 2024, View Source [SID1234648642]).

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"We are thrilled to offer an oral solution option for patients with leukemia and other cancers, a meaningful advancement for thousands in need," said Sharon Cunningham, chief executive officer of Shorla. "Oral solutions may ensure more precise and consistent dosing, offering a convenient alternative to compounding for patients who have difficulty swallowing or require dosing tailored to body surface area."

Leveraging Shorla’s novel technology, IMKELDI is an advanced liquid formulation of imatinib designed to provide dosing accuracy. IMKELDI can help slow or prevent the growth of specific cancers, including chronic myeloid leukemia (CML) and acute lymphoblastic leukemia, myelodysplastic syndrome /myeloproliferative disease (MDS/MPD), and gastrointestinal tumors (GIST).

In 2024, an estimated 9,280 people will be diagnosed with CML1, over 10,000 with MDS/MPD2, and up to 6,000 with GIST3 in the U.S. Despite the proven clinical benefits of imatinib, patient adherence can be an issue,4,5 underscoring a critical unmet need for a more accessible, patient-friendly oral solution delivery system.

"This milestone marks our fourth FDA approval as we advance our mission to make existing oncology treatments better through formulation re-innovation," said Orlaith Ryan, chief technical officer and co-founder of Shorla. "Our team is dedicated to creating more patient-friendly options that address real needs in those suffering from cancer."

Rayna Herman, chief commercial officer of Shorla added, "At Shorla, every innovation is driven by our commitment to put patients first. IMKELDI is another step forward as we continue to expand our growing portfolio with products that prioritize accessibility and affordability."

1. Key Statistics for Chronic Myeloid Leukemia. American Cancer Society. Updated January 17, 2024. Accessed November 7, 2024. View Source
2. Key Statistics for Myelodysplastic Syndromes. American Cancer Society. Updated January 22, 2018. Accessed November 7, 2024. View Source
3. Key Statistics for Gastrointestinal Stromal Tumors American Cancer Society. Updated January 26, 2021. Accessed November 7, 2024. View Source
4. Yanamandra U, Malhotra P, Sahu KK, et al. Variation in Adherence Measures to Imatinib Therapy. J Glob Oncol. 2018;4:1-10. doi:10.1200/JGO.2016.007906
5. Al-Barrak J, Cheung WY. Adherence to imatinib therapy in gastrointestinal stromal tumors and chronic myeloid leukemia. Support Care Cancer. 2013;21(8):2351-2357. doi:10.1007/s00520-013-1831-6

About IMKELDI

IMKELDI is an oral solution of imatinib mesylate, a tyrosine kinase inhibitor, approved by the U.S. Food and Drug Administration for use in certain forms of leukemia (such as acute lymphoblastic leukemia and chronic myeloid leukemia) and other cancers in adults and pediatric patients as young as one year old. Featuring a convenient, palatable strawberry flavor and a stable formulation that does not require refrigeration, IMKELDI offers a patient-friendly, precise treatment option designed to improve adherence and accessibility.