On April 8, 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 new preclinical data demonstrating proof-of-concept for its differentiated HER3-ADC program (Press release, Elevation Oncology, APR 8, 2024, View Source;utm_medium=rss&utm_campaign=elevation-oncology-presents-preclinical-proof-of-concept-data-for-her3-adc-program-at-aacr-annual-meeting-2024 [SID1234641864]). The data will be presented in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024, being held April 5-10 in San Diego, California.

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"We are pleased to share the first preclinical proof-of-concept data for our HER3-ADC program, reinforcing our commitment to advancing a portfolio of differentiated ADC-based therapies that may deliver better outcomes for patients," said David Dornan, Ph.D., Chief Scientific Officer of Elevation Oncology. "With our HER3-ADC program, we set out to design a differentiated ADC which selectively binds to HER3 and is internalized to potentially attack HER3-expressing cancerous cells while minimizing systemic exposure. Preclinical data with our proof-of-concept HER3-ADC shows HER3-dependent cell killing and robust anti-tumor activity in vivo where HER3 is expressed at high levels. We look forward to nominating a development candidate from our HER3 program later this year and, subsequently, advancing our program closer to the clinic."

HER3 is a clinically validated oncology and antibody-drug conjugate (ADC) target, which is overexpressed in a range of solid tumors, including breast cancer, EGFR-mutant non-small cell lung cancer and pancreatic cancer, and is often associated with poor clinical outcomes. Elevation Oncology’s HER3-ADC program conjugated seribantumab, its anti-HER3 monoclonal antibody, with a cleavable valine-citrulline linker and monomethyl auristatin E (MMAE) payload to yield HER3-ADC1, a proof-of-concept molecule with an average drug-antibody ratio (DAR) of 4.

In a poster titled, "Therapeutic potential of a HER3 antibody-drug conjugate for the treatment of HER3-expressing cancers," Elevation Oncology scientists presented in vitro and in vivo data of a seribantumab-based ADC for patients with HER3-expressing cancers. The data showed:

HER3-ADC1 binding to cancer cells, endocytosis, MMAE release and inhibition of proliferation were dependent on HER3 expression.
In cytotoxicity assays, HER3-ADC1 displayed HER3-dependent cell killing and outperformed a benchmark HER3-ADC with a deruxtecan payload, which is currently in clinical development.
In a patient derived xenograft (PDX) model of pancreatic cancer with high HER3 expression, HER3-ADC1 induced tumor regression, whereas an isotype-MMAE control and a benchmark HER3-ADC with a deruxtecan payload had only a modest effect.
The poster presentation is now available in the "Publications" section of Elevation Oncology’s website: View Source

On April 8, 2024 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated, localized biologics, reported the first patient has been dosed in a Phase 1 dose escalation study (NCT06265688) of CX-2051 in patients with advanced solid tumors (Press release, CytomX Therapeutics, APR 8, 2024, View Source [SID1234641863]). CX-2051 is a masked PROBODY antibody drug conjugate (ADC) directed toward epithelial cell adhesion molecule (EpCAM), a cell-surface target that is highly expressed across many cancer types including colorectal, gastric, endometrial, and ovarian cancers. The cytotoxic payload utilized in CX-2051 is a derivative of camptothecin, a topoisomerase-1 inhibitor, a class of drug that has shown potent clinical anti-cancer activity and demonstrated significant clinical benefit as an approved ADC in multiple cancers. The CX-2051 Phase 1 dose escalation is designed to efficiently test the safety and preliminary anti-tumor activity of CX-2051, to provide initial clinical proof of concept to inform a potential decision to move into dose expansions in 2025.

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"EpCAM is a high potential ADC target present at high levels on many solid cancers. CX-2051 has been optimized using our tailored masking strategies and possesses a potent cytotoxic payload ideally suited to specific EpCAM positive tumor types, including colorectal cancer. The successful initiation of the Phase 1 dose escalation study for CX-2051 is an important clinical milestone for CytomX as we continue to advance our multi-modality PROBODY therapeutic pipeline to address areas of significant unmet medical need," said Wayne Chu, M.D., chief medical officer of CytomX Therapeutics.

On April 8, 2024 Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of medications to treat severe endocrinologic, oncologic, metabolic and neurologic disorders by modulating the effects of the hormone cortisol, reported completion of enrollment in ROSELLA, a pivotal Phase 3 trial of its proprietary selective cortisol modulator relacorilant combined with nab-paclitaxel in patients with recurrent, platinum-resistant ovarian cancer (Press release, Corcept Therapeutics, APR 8, 2024, https://ir.corcept.com/news-releases/news-release-details/corcept-completes-enrollment-pivotal-phase-3-rosella-trial [SID1234641862]).

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"Fully enrolling ROSELLA takes us a big step closer to addressing the unmet medical need of women with platinum-resistant ovarian cancer," said Bill Guyer, PharmD, Corcept’s Chief Development Officer. "Relacorilant has the potential to become the standard of care for patients with this devastating disease. We expect progression-free survival data, ROSELLA’s primary endpoint, by the end of this year."

The ROSELLA trial has the same design as Corcept’s positive Phase 2 study, in which patients who received relacorilant intermittently – the day before, the day of and the day after they received nab-paclitaxel – exhibited improvements in progression-free survival, duration of response and overall survival compared to patients who received nab-paclitaxel alone, without an increased side effect burden. These results were published in the Journal of Clinical Oncology in June 2023.

The ROSELLA trial enrolled 381 women at sites in the United States, Europe, South Korea, Brazil, Argentina, Canada and Australia. Patients were randomized 1:1 to receive either relacorilant dosed intermittently with nab-paclitaxel or nab-paclitaxel monotherapy. ROSELLA’s primary endpoint is progression-free survival. Overall survival is a key secondary endpoint.

About Platinum-Resistant Ovarian Cancer
Ovarian cancer is the fifth most common cause of cancer death in women. Patients whose disease returns less than six months after receiving platinum-containing therapy have "platinum-resistant" disease. There are few treatment options and median overall survival following recurrence is 12 months or less with single-agent chemotherapy.1 In the United States, approximately 20,000 women with platinum-resistant disease are candidates to start a new therapy each year.

About Relacorilant
Relacorilant is a selective cortisol modulator that binds to the glucocorticoid receptor (GR), but does not bind to the body’s other hormone receptors. Corcept is studying relacorilant in a variety of serious disorders, including ovarian, adrenal and prostate cancer and Cushing’s syndrome. Relacorilant is proprietary to Corcept and is protected by composition of matter, method of use and other patents.

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.