On April 8, 2024 Coherus BioSciences, Inc. (Coherus, Nasdaq: CHRS), reported preclinical data for its immuno-oncology pipeline candidate, CHS-1000, a novel ILT4 monoclonal antibody, at the 2024 AACR (Free AACR Whitepaper) Annual Meeting being held in San Diego, California (Press release, Coherus Biosciences, APR 8, 2024, View Source [SID1234641861]). Data presented show CHS-1000 is a potent monoclonal antibody that binds selectively to human ILT4 (also known as LILRB2) with high affinity, efficiently blocking interaction with its ligands and reversing immunosuppressive functions, leading to activation of human dendritic cells and T cells and promoting polarization of macrophages to an inflammatory M1 phenotype.

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"Myeloid cell-mediated immunosuppression in the tumor microenvironment is a major contributor to tumor immune invasion and PD-1 resistance. The data presented in this poster demonstrate the potential for CHS-1000 to reverse myeloid suppression and activate an inflammatory immune response. Reprogramming myeloid cells in the tumor microenvironment holds promise as a new immuno-therapy approach with the aim to overcome resistance to I-O therapy and potentially provide benefit to more cancer patients," said Theresa LaVallee, Ph.D., Chief Development Officer at Coherus. "CHS-1000 is our first internally discovered development candidate, and we are excited to be filing the IND this quarter. We plan to advance CHS-1000 into the clinic both as a single agent and in combination with LOQTORZI."

These data will be presented today in a poster session, and the poster will be available for download at the time of the presentation:

Abstract: 1364/15
Title: Characterization of CHS-1000, an Fc-modified anti-ILT4 monoclonal antibody for reprogramming suppressive myeloid cells in solid tumors
Presenting author: Narendiran Rajasekaran, Ph.D.
Session PO.IM01.02 – Immune Checkpoints and Inhibitory Molecules 1
Date and Time: Monday, April 8, 2024, 9:00 a.m. – 12:30 p.m. Pacific Daylight Time

Poster data are summarized as follows:

CHS-1000 binds specifically and selectively to human ILT4 (LILRB2) with high affinity and showed no cross-reactivity to other LILRB family members.
CHS-1000 efficiently blocks the interaction of ILT4 with its ligands, HLA-A and HLA-G, and reverses ILT4-mediated immunosuppressive functions, leading to activation of M1 macrophages, dendritic cells, and T cells and increases in pro-inflammatory cytokine secretion in in vitro assays.
CHS-1000 is Fc silent and lacks effector function activity in in vitro assays consistent with the engineered modification of the Fc region of the antibody. It also has IgG1‑like PK parameters in human FcRn transgenic mice.
ILT4 and CD163, a marker of suppressive (M2) macrophages, are highly expressed in a broad range of solid tumors.

About CHS-1000

Discovered and developed by Coherus, CHS-1000 is a novel humanized Fc-modified IgG1 monoclonal antibody specifically targeting ILT4 (LILRB2). CHS-1000 is designed to overcome myeloid cell-mediated immunosuppression and resistance in the tumor microenvironment. In preclinical studies, CHS-1000 promotes repolarization of suppressive M2 macrophages to a pro-inflammatory M1 phenotype and enhances activation of dendritic cells and T cells in vitro. Coherus plans to file an investigational new drug (IND) application in Q2 2024 and begin clinical studies later this year.

On April 8, 2024 Celularity Inc. (NASDAQ: CELU) ("Celularity"), a biotechnology company developing placental-derived allogeneic cell therapies and advanced biomaterial products, reported that it will present in vitro data from its investigational natural killer (NK) cell therapy programs at this year’s American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting (Press release, Celularity, APR 8, 2024, View Source [SID1234641860]). The preclinical data, which suggest that Celularity’s placenta-derived unmodified natural killer (NK) cells (CYNK-001) and genetically modified NK cells (CYNK-201) may serve as potent and selective senolytic agents for use in addressing age-related diseases, will be presented on May 9, 2024.

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Senescent cells are key drivers in the process of age-related cellular corruption at the heart of degenerative diseases, cancer and immuno-senescence (the progressive decline in immune function that occurs with age). These cells are unique in that they eventually stop multiplying but do not die; instead, they transform into the senescence associated secretory phenotype (SASP) and continue to release chemicals that can promote inflammation and tumor progression. Moreover, if not eliminated, these cells impair the normal regenerative process that restores function to organs and tissues.

Celularity is building a broad technology platform that leverages the placenta’s unique immunobiology as a source of highly expandable, off-the-shelf cells, as well as a diverse portfolio of cell therapy investigational products to address age-related diseases, including cancer and degenerative diseases. Celularity believes these preclinical data demonstrate the potential of its assets to target and selectively remove damaged and abnormal cells expressing stress ligands, such as senescent, virally infected and cancer cells.

"Celularity believes in the broad, but so far underrealized, potential of cell therapies. We continue to investigate cellular immunotherapy in age-related diseases, and these data are an important, continued step in demonstrating how our therapeutic assets may be used to eliminate senescent cells," said Celularity’s CEO and Founder Dr. Robert Hariri, M.D., Ph.D. "Removing these aging, senescent cells, which we have termed ‘senoablation,’ may represent an important clinical approach to address the high societal cost of age-associated diseases and disabilities."

The ASGCT (Free ASGCT Whitepaper) Annual Meeting will take place on May 7 through 11, 2024, in Baltimore, Md.

On April 8, 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 that preliminary data exploring novel TALEN editing process in hematopoietic stem and progenitor cells (HSPCs) will be presented at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 27th Annual Meeting, to be held in Baltimore, Maryland, on May 7-11, 2024 (Press release, Cellectis, APR 8, 2024, View Source [SID1234641859]).

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Poster presentations:

Title: Circularization of Non-Viral Single-Strand DNA Template for Gene Correction and Gene Insertion Improves Editing Outcomes in HSPCs

Presenter: Alex Boyne, Gene Editing Platform Manager at Cellectis
Session Date/Time: May 9, 2024 at 12PM ET
Session Title: Nonviral Therapeutic Gene Delivery and Synthetic/Molecular Conjugates
Presentation Room: Exhibit Hall
Final Abstract Number: 1235

Cellectis presents the development of a novel gene editing process, leveraging the TALEN technology and non-viral DNA template delivery, enabling highly efficient gene correction and gene insertion in hematopoietic stem and progenitor cells (HSPCs).

Title: Intron Editing of HSPC Enables Lineage-Specific Expression of Therapeutics

Presenter: Julien Valton, Ph.D., Vice President Gene Therapy at Cellectis
Session Date/Time: May 5, 2024 at 12PM ET
Session Title: Gene Targeting and Gene Correction New Technologies
Presentation Room: Exhibit Hall
Final Abstract Number: 721

Gene therapy using hematopoietic and progenitor stem cells (HSPC) has the potential to provide a lifelong supply of genetically encoded therapeutics. Gene editing strategies enabling supra-endogenous expression of therapeutics often rely on constitutive promoters resulting in transgene overexpression irrespective of cellular differentiation, which could be detrimental for HSPC function. Cellectis presents the development of a TALEN mediated promoter-less intron editing strategy that relies on the endogenous cellular RNA splicing machinery to induce lineage-specific transgene expression exclusively after HSPC differentiation.

Full abstracts and presentations will be available on Cellectis’ website following the event:
View Source

On April 8, 2024 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported the presentation of five abstracts at the American Association for Cancer Research (AACR) (Free AACR Whitepaper), taking place from April 5-10, 2024, in San Diego, California (Press release, Cardiff Oncology, APR 8, 2024, View Source [SID1234641858]). In combination, the abstracts underscore the significant potential of the company’s lead molecule onvansertib in metastatic colorectal cancer (mCRC) and other cancers.

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"Overall, the totality of our preclinical and clinical data we are presenting at AACR (Free AACR Whitepaper) in mCRC is promising and provides scientific validation of our ongoing first-line RAS-mutated mCRC trial, where all patients have no prior exposure to bevacizumab, meaning they are bev naïve," said Mark Erlander, Ph.D., Chief Executive Officer of Cardiff Oncology. "Furthermore, bev naïve patients in our Phase 1b/2 KRAS-mutated mCRC trial were approximately 4 times (73 % vs 19%) more likely to achieve a clinical response compared to bev exposed patients in the dataset presented at AACR (Free AACR Whitepaper). This is consistent with the data we later generated from our randomized ONSEMBLE trial in RAS-mutated mCRC, which serves as a second independent data set reproducing the robust efficacy signal for onvansertib plus standard of care in bev naïve patients. In addition, we are particularly encouraged by our RAS-mutated mCRC preclinical data highlighting onvansertib’s ability to inhibit activation of the hypoxia pathway via the regulation of HIF1α. We believe this mechanism acts complementary to bevacizumab, potentially providing an even greater reduction in tumor vascularization when the two agents are combined."

Key highlights from the company’s five poster presentations at AACR (Free AACR Whitepaper) are below.

A Phase 1b/2 Clinical Study of Onvansertib in Combination with FOLFIRI/Bev Revealed a New Role of PLK1 in regulating the Hypoxia Pathway in KRAS-mutated Metastatic Colorectal Cancer
•Bev naïve patients treated with onvansertib + FOLFIRI/bev demonstrated a significantly greater overall response rate [odds ratio=13.64, p<0.001] and longer PFS [hazard ratio=0.21, p=0.003] compared to bev exposed patients.
•Onvansertib reduced tumor vascularization as a single agent and onvansertib + bev combination resulted in a greater decrease in tumor vascularization.
•In vitro, onvansertib inhibited the activation of the hypoxia pathway through the regulation of the transcription factor HIF1α and its downstream targets.
•Collectively the updated clinical and preclinical data further support the ongoing CRDF-004, Phase 2 trial of onvansertib + chemo/bev for the first-line treatment of RAS-mutated mCRC patients, who by definition are bev naïve.

A Phase 2, Randomized, Open-label Study of Onvansertib in Combination with Standard-of-Care (SoC) Versus SoC Alone for First-line Treatment of RAS-mutated Metastatic Colorectal Cancer
•CRDF-004 is a Phase 2 randomized trial generating preliminary safety and efficacy data and evaluating two different doses of onvansertib to confirm an optimal dose. Onvansertib will be added to standard-of-care consisting of FOLFIRI plus bev, or FOLFOX plus bev.
•A total of 90 patients will be randomized in a 1:1:1 ratio to either 20mg of onvansertib plus standard-of-care, 30mg of onvansertib plus standard-of-care, or standard-of-care alone.
•The primary endpoint of the study includes objective response rate (ORR), and the key secondary endpoints include progression-free survival (PFS) and duration of response (DoR).

The PLK1 Inhibitor Onvansertib is Active as Monotherapy and in Combination with Cetuximab
In RAS Wild-type Metastatic Colorectal Cancer Patient-derived Xenografts
•Single agent onvansertib successfully induced tumor stasis or regression in 70% (14/20) of the RAS WT mCRC patient-derived xenograft (PDX) models tested. This included both models sensitive to cetuximab (5/7, 71%) and resistant to cetuximab (9/13, 69%).
•Onvansertib in combination with cetuximab induced tumor stasis or regression in 90% (18/20) of the models tested.
•Overall, the antitumor activity of the combination was superior compared to monotherapy with either agent in both cetuximab sensitive and resistant models.
The PLK1 Inhibitor, Onvansertib, Synergizes with Paclitaxel in Small Cell Lung Cancer (SCLC)
•Onvansertib in combination with paclitaxel was well-tolerated and demonstrated superior efficacy over monotherapies in cisplatin sensitive and resistant SCLC PDX models.
•In cisplatin-resistant models, onvansertib plus paclitaxel led to tumor regression, with effects lasting 2 months post-treatment.
•Collectively, these preclinical findings in SCLC and previous data generated in breast cancer suggest that onvansertib in combination with paclitaxel has the potential to become a highly promising combination strategy across multiple cancer indications.

In vivo anti-tumor activity of onvansertib, a PLK1 inhibitor, combined with gemcitabine or carboplatin in platinum-resistant ovarian carcinoma patient-derived xenograft models
•Onvansertib was synergistic in vitro in combination with carboplatin or gemcitabine in an ovarian cancer cell line.
•Both combinations demonstrated antitumor activity in vivo in platinum-resistant ovarian cancer PDX models and were well tolerated.
•These data support the potential of onvansertib to improve SoC treatments of platinum-resistant ovarian cancer patients.
All the abstracts are available on the AACR (Free AACR Whitepaper) Online Program and will be published in the online Proceedings of the AACR (Free AACR Whitepaper). Following the presentation, the posters will be posted to the "Scientific Presentations" section of the Cardiff Oncology website.

On April 8, 2024 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science, reported a poster today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 highlighting new preclinical data for CFT1946 across multiple models of BRAF V600X mutant colorectal cancer (CRC) and non-small cell lung cancer (NSCLC), additional BRAF inhibitor (BRAFi)-resistant melanoma models, and an intracranial model of BRAF V600E metastatic melanoma (Press release, C4 Therapeutics, APR 8, 2024, View Source [SID1234641857]).

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CFT1946 is an orally bioavailable BiDAC degrader that selectively degrades the BRAF V600X mutant protein and prevents RAF dimer-mediated resistance. While currently approved BRAF inhibitors are also selective for BRAF V600X mutant proteins, their activity is limited by primary or acquired resistance often mediated by mechanisms that promote RAF dimerization. Further, in a significant number of patients with BRAF V600X melanoma and NSCLC, the disease metastasizes to the brain. BRAF inhibitors have limited brain penetration, while CFT1946 demonstrates CNS activity in preclinical models.

Key findings include:

Promising activity of CFT1946 as a single agent in a broad range of BRAF V600X preclinical models, including models of BRAFi resistance.
CFT1946 as a single agent and in combination with cetuximab demonstrates superior activity to the standard of care combination, BRAFi with cetuximab, in all CRC models tested to date, further supporting the potential of a degrader advantage in this setting.
CFT1946 demonstrates superior prolongation of survival when compared to encorafenib in an intracranial model of metastatic melanoma.
Collectively, these data support the ongoing clinical evaluation of CFT1946, which is the only BRAF V600X degrader in the clinic to date. The CFT1946 Phase 1/2 trial continues to progress and data from the Phase 1 monotherapy dose escalation portion of the trial are expected to be presented in the second half of this year.

Details of the poster are as follows:

Title: CFT1946, a potent, selective BRAF V600X mutant-specific degrader demonstrates superior activity as a single agent to clinically approved BRAF inhibitors and standard of care combinations in preclinical models of BRAF V600X melanoma, CRC, NSCLC, and brain metastasis
Abstract Number: 1658
Session Date and Time: Monday April 8, 2024 9:00 AM – 12:30 PM PT
Location: Poster Section 14
Session Title: Cell Signaling Components as Therapeutic Targets
Presenter: Bridget Kreger, Ph.D., principal scientist, biology

The poster will be made available after the presentation under the scientific presentations and publications page of the company’s website at www.c4therapeutics.com.