On December 09, 2024 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported the company and its research collaborators will present data demonstrating the benefits of its precision oncology tests, real-world clinical-genomic database and AI analytics in optimizing therapy selection, identifying resistance mutations, and predicting long-term outcomes at the San Antonio Breast Cancer Symposium (SABCS) 2024 in San Antonio, Texas, Dec. 10-13, 2024 (Press release, Guardant Health, DEC 9, 2024, View Source [SID1234648957]).

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Guardant and its research partners will present eight posters, including an SABCS Poster Spotlight featuring the use of the Guardant Reveal test, a tissue-free epigenomic assay, to investigate the dynamics of circulating tumor DNA (ctDNA) during neoadjuvant endocrine therapy in HR+ early breast cancer. Study findings suggest that ctDNA has the potential to provide valuable insights into tumor burden, sensitivity to endocrine therapy, and the emergence of endocrine resistance mutations. The investigators conclude that ctDNA could be a valuable tool in predicting long-term outcomes and in tailoring treatment approaches.

"Working together with our research collaborators, we continue to establish the important role of Guardant’s precision oncology portfolio in informing treatment selection and monitoring for recurrence and therapeutic response," said Craig Eagle, M.D., chief medical officer at Guardant Health. "We look forward to sharing new studies at SABCS that show how Guardant is working with researchers and cancer care teams to improve outcomes for people living with breast cancer."

Guardant Health and collaborator poster presentations at SABCS 2024

Wednesday, December 11 | 7:00-8:30 am | Hemisfair Ballroom 1-2

Abstract

Title

Product

PS7-05

SABCS Poster Spotlight

Impact of prior treatment, ESR1 mutational (ESR1m) landscape, and co-occurring PI3K pathway status on real-world (RW) elacestrant outcomes in patients (pts) with hormone receptor-positive (HR+)/HER2-negative advanced breast cancer (aBC)

GuardantINFORM

Wednesday, December 11 | 12:30 – 2:00 pm | Halls 2-3

P1-01-24

Genomic comparison of rapid vs. typical progressors on CDK4/6 inhibitor treatment in advanced breast cancer

GuardantINFORM

P1-05-30

A statistical model for integration of on-treatment circulating tumor DNA dynamics and prediction of outcomes in patients with ER+/HER2- metastatic breast cancer

Guardant Infinity

P1-10-05

Real-world molecular profiling after CDK4/6 inhibition in advanced breast cancer: analysis of the SOLTI-1903 HOPE study

Guardant360 CDx

Wednesday, December 11 | 5:30-7:00 pm | Halls 2-3

P2-05-20

Tissue-free minimal residual disease testing in 2,000 consecutive patients with breast cancer: real-world data and case report

Guardant Reveal

Thursday, December 12 | 7:00-8:30 am | Stars at Night 3-4

PS9-04

SABCS Poster Spotlight

Evaluating racial genomic differences in de novo metastatic breast cancer utilizing ctDNA: results from a large multi-center consortium

Guardant360

PS9-08

SABCS Poster Spotlight

Ultra-sensitive detection of circulating tumor DNA (ctDNA) in patients (pts) undergoing neoadjuvant endocrine therapy for hormone receptor-positive (HR+) early breast cancer (BC)

Guardant Reveal

Thursday, December 12 | 5:30-7:00 pm | Halls 2-3

P4-01-19

Clinical impact of MRD detection via ctDNA tumor-agnostic assay in early-stage breast cancer patients: a real-world experience

Guardant Reveal

The full abstracts for Guardant Health and a list of all abstracts being presented at SABCS 2024 can be found on the SABCS website.

For information and updates from the conference, visit booth 1424 and follow Guardant Health on LinkedIn, X (Twitter) and Facebook.

On December 9, 2024 Orna Therapeutics, a biotechnology company dedicated to designing and delivering a new class of circular RNA medicines and unprecedented lipid nanoparticle (LNP) delivery solutions for oncology and autoimmune diseases, reported a poster highlighting new preclinical data that demonstrates the potential of its in vivo panCAR platform for the treatment of B cell mediated diseases at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place in San Diego from December 7-10, 2024 (Press release, Orna Therapeutics, DEC 9, 2024, View Source [SID1234648910]).

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Orna’s lead LNP candidate, demonstrated effective delivery of oRNA cargo to 60% of splenic T cells and 84% of peripheral blood T cells in non-human primates (NHPs). When paired with an oRNA cargo, the Company’s LNP demonstrated up to ~70% delivery of an anti-CD20 CAR to NHP T cells and human T cells in vitro and maintained expression over 72 hours. A single dose of the anti-CD20 panCAR resulted in a 95% reduction in NHP B cells, with sustained depletion (82%) observed 7 days after dosing.

"Our panCAR approach combining a synthetic, circular coding RNA platform oRNA and proprietary immunotropic LNP holds the potential to deliver an entirely novel class of in vivo CAR therapies that eliminate lengthy patient cell processing and lymphodepletion regimens," said Joe Bolen, Ph.D., Chief Scientific Officer for Orna. "The data presented today at ASH (Free ASH Whitepaper) further validate our hypothesis, demonstrating our ability to effectively deliver oRNA cargo and achieve robust and sustained B cell depletion in NHPs, highlighting the potential of our work in advancing our in vivo CAR therapies across both cancer and autoimmune diseases towards the clinic."

Additional key findings are as follows:

In cytotoxicity assays, both the anti-CD20 CAR and an anti-CD19 CAR construct killed human B lymphoblast cell lines in vitro.
In vivo, both the anti-CD19CAR and anti-CD20 CAR oRNAs showed significant B cell depletion that manifested as a 75-80% reduction in B cells in peripheral blood, spleen, and bone marrow at 24 hours. This effect was sustained for 7 days after dosing in peripheral blood and bone marrow.

On December 9, 2024 Medigene AG (Medigene or the "Company", FSE: MDG1, Prime Standard), an oncology platform company focused on the research and development of T cell receptor (TCR)-guided therapies for the treatment of cancer, reported the selection of Kirsten rat sarcoma viral oncogene homologue (KRAS) G12V, in the context of HLA*A11, as the initial target for the co-development of T cell receptor-guided T cell engagers (TCR-TCEs) with WuXi Biologics (Press release, MediGene, DEC 9, 2024, View Source [SID1234648926]).

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The selection of this first target is a key step for the partnership between Medigene and WuXi Biologics, which aims to advance multiple TCR-TCEs over the next three years. The collaboration seeks to harness Medigene’s expertise in the generation and characterization of highly sensitive, specific and safe (3S) TCRs with WuXi Biologics’ unique anti-CD3 monoclonal antibody (mAb), its TCE platform and proprietary bispecific antibody platform WuXiBody.

"Rapid selection of KRAS G12V as the target for this first program, also known as MDG3010 in Medigene’s pipeline, marks the initial step for the development of a TCR-TCE library for the treatment of difficult-to-treat tumors. This fast program progression reflects the highly effective collaboration between the teams," said Selwyn Ho, CEO of Medigene. "We believe that the combination of Medigene’s 3S TCR and WuXi Biologics’ CD3 mAb and bispecific platform offers the potential of a best-in-class therapeutic that precisely targets broad numbers of patients expressing this validated common KRAS mutation, in an off-the-shelf administration."

KRAS mutations are widely recognized as the most common oncogene mutations and play a significant role in indications that affect a large number of patients, such as pancreatic, small bowel, colorectal, and lung cancers.1 In pancreatic cancer, KRAS mutations are among the earliest and most critical genetic alterations, present in over 95% of cases; here, G12D and G12V are the most frequent (~65%).2,3 In 2020, pancreatic cancer was the seventh leading cause of cancer-related deaths globally for both men and women, with nearly as many newly diagnosed patients (496,000) as deaths (466,000) from this single indication.4

The bispecific therapies market offers a significant opportunity in the fight against cancer, addressing the unmet need in both solid and hematologic tumors. Over 5 million cancer patients worldwide face low five-year survival rates, highlighting the urgent demand for innovative treatments. Bispecific TCR-TCEs, which harness the immune system to target cancer cells more precisely, are projected to grow at a compound annual rate of 40.9% from 2023 to 2030. By 2030, the market is expected to surpass USD 80 billion5, reflecting its potential to transform cancer treatment and improve patient outcomes.

On December 9, 2024 Solu Therapeutics, a biotechnology company pioneering therapies to eliminate disease-driving cells in cancer, immunology, and other therapeutic areas, reported positive preclinical data on STX-0712, its novel CCR2-CyTAC (Cytotoxicity Targeting Chimera), for the treatment of chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) (Press release, Solu Therapeutics, DEC 9, 2024, View Source [SID1234648942]). Results were presented over the weekend in two poster sessions at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, held December 7-10, 2024, in San Diego, California.

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"The encouraging results from our preclinical studies in CMML and AML highlight the unique power of our CyTAC platform to precisely target and eliminate disease-driving cells," said Sergio Santillana, Chief Medical Officer of Solu. "STX-0712’s ability to selectively target CCR2-positive malignant monocytes in these two challenging blood cancers showcases the platform’s potential to support the development of transformative treatments for different types of cancer and other diseases. We look forward to advancing STX-0712 into clinical trials and continuing to leverage our platform for other high-need diseases."

Preclinical Results for STX-0712 in CMML
Key Findings:

CCR2 was highly expressed in >98% of malignant monocytes in peripheral blood and in a subset of CD34+ progenitors in the bone marrow of CMML patients, while minimal or no CCR2 expression was observed in CD34+ progenitor healthy controls.

In all patient samples tested, STX-0712 effectively depleted CD14+CCR2+ monocytes, achieving 66–91% cancer cell elimination with an average potency of 3nM.

In non-human primates (NHPs), STX-0712 demonstrated potent dose-dependent activity, effectively depleting more than 95% of CCR2-positive monocytes.

STX-0712 exhibited favorable pharmacokinetics in NHPs and was well tolerated, with no adverse effects observed.
To access the full abstract, click here.

Preclinical Results for STX-0712 in AML
Key Findings:

CCR2 was highly expressed on malignant monocytes from AML patient samples, with cases of acute monocytic leukemia (M5) and acute myelomonocytic leukemia (M4), showing the highest levels of expression.

STX-0712 successfully eliminated CCR2-positive malignant monocytes in 80% of patient samples, with up to 74% of cancer cells depleted and an average potency of 3nM.

When combined with venetoclax and azacitidine (standard-of-care treatments for AML), STX-0712 improved therapeutic efficacy in 60% of patient samples by differential targeting both CCR2-positive monocytes and undifferentiated blasts.

Minimal effects were observed on non-target populations such as lymphocytes and CCR2-negative CD34+ blasts, demonstrating the high selectivity of STX-0712.
To access the full abstract, click here.

"The results from these studies represent a significant milestone for Solu, as they reinforce the potential of STX-0712 in the treatment CMML and AML, two diseases with limited targeted therapies available," said Brandon Turunen, Co-founder, Chief Technology Officer, and Head of Drug Discovery at Solu. "By targeting the underlying drivers of these diseases, STX-0712 could offer a highly targeted approach to treatment while maintaining a strong safety profile. We look forward to advancing this promising program to clinical-stage research in 2025."

About STX-0712

STX-0712 is a CyTAC targeting the G-Protein Coupled Receptor (GPCR) CCR2, a selective marker expressed at high levels on malignant monocytes that are key drivers in certain hematologic cancers. By targeting CCR2, STX-0712 is designed to selectively eliminate these malignant cells.

On December 09, 2024 Synthekine Inc., an engineered cytokine therapeutics company, reported positive initial results from a first-in-human Phase 1 study (NCT05665062) of SYNCAR-001 + STK-009 for the treatment of relapsed or refractory CD19+ hematologic malignancies (Press release, Synthekine, DEC 9, 2024, View Source [SID1234648958]). In the results presented from 8 patients treated in the dose escalation portion of the study with a fixed SYNCAR-001 infusion of 30M cells and STK-009 doses ranging from 1.5 to 6 mg, this combination therapy was well tolerated with no dose-limiting toxicities (DLTs) or IL-2-related toxicities observed. This regimen also demonstrated durable responses, including complete responses in all 4 patients with non-Hodgkin lymphoma (NHL).

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The data were presented by Lia Palomba, M.D., Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego. The poster will also be part of the ASH (Free ASH Whitepaper) Poster Walk on Blood Immunology & Cellular Therapy: Advancing Innovations and Translational Insights hosted by Blood Immunology & Cellular Therapy today from 7:30 a.m. to 8:30 a.m. PT.

"Enhancing CAR-T cells with consistent cytokine support, particularly IL-2, has the potential to significantly improve their therapeutic effect. However, prolonged wild-type IL-2 administration is currently not feasible due to severe toxicities like capillary leak syndrome (CLS)," said Dr. Palomba. "SYNCAR-001 + STK-009 represents an innovative solution, enabling the targeted delivery of a potent and durable IL-2 signal specifically to CAR-T cells in vivo and avoiding activation and proliferation of native lymphocytes that can cause CLS. Based on the data presented at ASH (Free ASH Whitepaper), we are encouraged by SYNCAR-001 + STK-009’s favorable safety and efficacy profile and its potential to treat patients with relapsed or refractory B cell malignancies."

SYNCAR-001 + STK-009 is a cytokine-enabled cell therapy regimen based on Synthekine’s proprietary orthogonal IL-2 technology. It is a two-component therapy consisting of SYNCAR-001, an autologous CD19-targeting chimeric antigen receptor T (CAR-T) cell which expresses an engineered IL-2 receptor, and STK-009, an engineered pegylated IL-2 cytokine that selectively signals through the engineered IL-2 receptor.

"The data presented at ASH (Free ASH Whitepaper) is important validation of our orthogonal IL-2 technology. Consistent with our preclinical observations, the combination of STK-009 and a low dose of SYNCAR-001 cells demonstrates robust cell expansion and persistence, potent cytotoxic activity, and durable cell fitness," said Debanjan Ray, chief executive officer of Synthekine. "We are excited to report that STK-009 selectively delivered IL-2’s proliferation and activation signal to SYNCAR-001 cells without the toxicities, including CLS, that are typically associated with wild-type IL-2 treatment. Furthermore, the ability of STK-009 to provide an IL-2 signal exclusively to SYNCAR-001 cells may allow us to bypass the need for potentially toxic lymphodepleting chemotherapy (LDC). We are now enrolling patients to this trial without LDC and have recently opened a trial in autoimmune diseases also without LDC."

SYNCAR-001 + STK-009 INITIAL PHASE 1 DOSE ESCALATION DATA IN CD19+ HEMATOLOGIC MALIGNANCIES

As of the October 8, 2024, data cutoff, 8 patients have been treated in the dose escalation portion of the study. Following a standard regimen of cyclophosphamide/fludarabine (cy/flu), patients received a fixed dose of 30 million SYNCAR-001 cells and doses of STK-009 at 1.5 mg (n=3), 3 mg (n=3) and 6 mg (n=2)
All patients were CAR-T naïve. Four patients had non-Hodgkin lymphoma (NHL) and four patients had chronic lymphocytic leukemia (CLL)
Complete response (CR) was observed in all 4 patients with NHL, and 1 patient with CLL had stable disease (SD) as best overall response
Responses were durable and ongoing in all 4 patients with NHL who exhibited CRs, with the longest duration of CR extending beyond 480 days
Majority of adverse events (AEs) were Grade 1 or 2; the most common AEs were cytopenias expected to occur with cy/flu treatment
Limited, mild-moderate cytokine release syndrome (CRS) was observed in 4 patients (maximum Grade 2); Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 1 patient
A high proportion of SYNCAR-001 cells sustain a long-lasting central memory phenotype on STK-009 treatment
Only minimal exhaustion and senescence of SYNCAR-001 cells was observed throughout the course of STK-009 treatment
In addition to this trial, a Phase 1 study (NCT06544330) of SYNCAR-001 + STK-009 in non-renal systemic lupus erythematosus and lupus nephritis is enrolling subjects, and received Fast Track designation from the U.S. Food and Drug Administration (FDA) in September 2024.