ozekibart (INBRX-109) / Inhibrx Biosci, Transcenta - LARVOL DELTA

Inhibrx Reports First Quarter 2025 Financial Results (PRNewswire) - "Upcoming Milestones: INBRX-109: (i) Data from the registration-enabling Phase 2 trial in unresectable or metastatic conventional chondrosarcoma are expected during the third quarter of 2025; and (ii) Initial data on the colorectal cancer expansion cohort are anticipated in the third quarter of 2025 with interim data from the Ewing sarcoma expansion cohort expected in the second half of 2025."

Clinical data • Chondrosarcoma • Colorectal Cancer • Ewing Sarcoma

Recent Advances in Succinate Dehydrogenase Deficient Gastrointestinal Stromal Tumor Systemic Therapies. (PubMed, Curr Treat Options Oncol) - "In our current practice we typically treat advanced symptomatic SDH-Def GIST with the anti-angiogenic TKIs, sequentially treating with sunitinib, regorafenib and pazopanib...Olverembatinib and rogaratinib have shown promising activity in pre-clinical models and small SDH-Def GIST cohorts. Other agents whose benefits are explored here include the immune checkpoint inhibitors (ICI) ipilimumab and nivolumab and temozolomide, whether as monotherapy or in combination with INBRX-109 (a pro-apoptotic antibody) or olaparib. Additional research into TKI agents with anti-vascular endothelial growth factor receptor (VEGFR) and anti-fibroblast growth factor receptor (FGFR) activity in this clinical setting is needed. Patients with SDH-Def will benefit more broadly from ongoing explorations of treatments with alternative mechanisms of action, especially those that exploit cellular pathways involved in SDH-Def GIST tumorigenesis."

Journal • Review • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Metabolic Disorders • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • FGFR

Inhibrx Reports Fourth Quarter and Fiscal Year 2024 Financial Results (PRNewswire) - "Research and development expenses were $203.7 million during the fiscal year 2024 as compared to $191.6 million during the fiscal year 2023, primarily due to the following factors: an increase in clinical trial expenses primarily due to the ongoing registration-enabling Phase 2 trial for ozekibart (INBRX-109) for the treatment of unresectable or metastatic conventional chondrosarcoma and due to the expansion of the INBRX-106 Phase 1/2 trial and initiation of the Phase 2/3 trial for HNSCC, including expenses for in-house clinical trial support. These increases were offset in part by a decrease in clinical trial expenses as a result of the termination of the INBRX-105 program."

Commercial • Chondrosarcoma • Squamous Cell Carcinoma of Head and Neck

Tetravalent death receptor 5 (DR5) agonist ozekibart (INBRX-109) + FOLFIRI in 2L+ colorectal adenocarcinoma (CRC): Preliminary results from a phase 1 study. (ASCO-GI 2025) - P1, P2 | "Pts with locally advanced or metastatic, unresectable CRC who received oxaliplatin-based chemo were eligible for part 3... Ozekibart + FOLFIRI showed encouraging preliminary efficacy, including PRs and durable disease control, as 2L+ therapy in pts with CRC. Given these promising data, a new expansion cohort (C4d) is open to validate these findings in a more homogeneous population. Eligible pts will have had 2 or 3 prior lines of systemic therapy (irinotecan allowed but not in the immediately prior line) and must have archival or fresh biopsy tissue."

P1 data • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • TNFRSF10B

Inhibrx Biosciences Announces Preliminary Data from the Phase 1 Trial of ozekibart (INBRX-109) for the Treatment of Colorectal Cancer (PRNewswire) - P1 | N=321 | NCT03715933 | Sponsor: Inhibrx Biosciences, Inc | "These results were presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Annual Cancers Symposium. Efficacy was assessed in 10 of the 13 patients who received at least one dose of ozekibart....Results demonstrated one complete response (CR), three partial responses (PR), and six cases of stable disease (SD). Durable disease control lasting ≥180 days was observed in 46.2% of patients, with a median progression-free survival (PFS) of 7.85 months.....Notably, the patient achieving a CR had undergone three prior lines of therapy, and two PRs occurred in patients who had failed prior FOLFIRI-based treatments....Inhibrx has initiated a new expansion cohort to validate these findings in a more uniform patient population. The cohort is expected to enroll up to 50 patients, each with two to three prior lines of systemic therapy, and data are anticipated in Q3 2025."

P1 data • Trial status • Colorectal Adenocarcinoma

Inhibrx Biosciences Announces Loan Agreement with Oxford Finance (PRNewswire) - "Inhibrx Biosciences...announced it entered into a loan and security agreement (the 'LSA') with Oxford Finance LLC ('Oxford', together with certain of its affiliates party thereto, the 'Lenders'), pursuant to which the Lenders provided a five-year term loan facility for up to $150 million (the 'Credit Facility'). 'This enables us strategic flexibility post data readouts expected later this year for our INBRX-109 and INBRX-106 programs'....'The INBRX-109 and INBRX-106 programs have shown highly promising clinical results, and we look forward to supporting Inhibrx as it advances its pipeline and further develops these innovative therapies'."

Commercial • Solid Tumor

ChonDRAgon: Study of INBRX-109 in Conventional Chondrosarcoma (clinicaltrials.gov) - P2 | N=201 | Recruiting | Sponsor: Inhibrx Biosciences, Inc | Trial completion date: Jul 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Sep 2025

Trial completion date • Trial primary completion date • Oncology • Sarcoma • Solid Tumor

Phase 1 Study of INBRX-109 in Subjects with Locally Advanced or Metastatic Solid Tumors Including Sarcomas (clinicaltrials.gov) - P1 | N=321 | Recruiting | Sponsor: Inhibrx Biosciences, Inc | N=240 ➔ 321 | Trial completion date: Jul 2026 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Jun 2026

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Ewing Sarcoma • Gastric Cancer • Mesothelioma • Oncology • Sarcoma • Solid Tumor

Advancing Systemic Therapy in Chondrosarcoma: New Horizons. (PubMed, Oncol Ther) - "Among new approaches, DR5 agonists such as INBRX-109 have shown single-agent efficacy, with minimal toxicity, opening possibilities for use in combination therapies to improve outcomes...The integration of multi-targeted approaches could enhance efficacy, address tumour heterogeneity, and overcome resistance, presenting a hopeful direction for systemic therapy in this challenging cancer. The investigation of combination regimens with IDH inhibitors, immunotherapy and DR5 agonists hold promise for transforming the management of advanced chondrosarcoma."

IO biomarker • Journal • Immune Modulation • Immunology • Oncology • Sarcoma • Solid Tumor • TNFRSF10B

THE TETRAVALENT DEATH RECEPTOR 5 AGONIST OZEKIBART INBRX-109) IN PATIENTS WITH CHONDROSARCOMA: UPDATED RESULTS FROM A PHASE 1 STUDY (CTOS 2024) - P1, P2 | "Consistent with the prior analysis, INBRX-109 was found to be well tolerated, and no new safety signals were observed. INBRX-109 continued to demonstrate encouraging clinical efficacy in patients with unresectable or metastatic CS, regardless of IDH mutation status, and median PFS remained greater compared to historical data ( < 4 months). These results are being confirmed in a randomized, blinded, placebo-controlled, phase 2 trial of INBRX-109 in unresectable or metastatic conventional CS (ChonDRAgon, NCT04950075), which is currently enrolling in the US, Europe, and Australia."

Clinical • P1 data • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • IDH1 • IDH2 • TNFA • TNFRSF10B

Inhibrx Biosciences Reports Third Quarter 2024 Financial Results (PRNewswire) - "Inhibrx Biosciences...the biopharmaceutical company now has two programs in ongoing clinical trials, with data readouts for each expected within the next 12 months...R&D Expense. Research and development expenses were $38.9 million during the third quarter of 2024, compared to $38.1 million during the third quarter of 2023. The increase in research and development expenses was primarily due to: an increase in clinical trial expenses due to the expansion of the Company's ongoing registration-enabling Phase 2 trial for ozekibart (INBRX-109) for the treatment of unresectable or metastatic conventional chondrosarcoma. Clinical trial expenses also increased as a result of the expansion of the INBRX-106 Phase 1/2 trial and the initiation of the Phase 2/3 trial in head and neck squamous cell carcinoma, including expenses for in-house clinical trial support."

Clinical data • Commercial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Targeting Death Receptor 5 (DR5) for imaging and treatment of primary bone and soft tissue tumors: an update of the literature. (PubMed, Front Mol Biosci) - "The combination of DR5 agonists and commonly used chemotherapeutic agents, such as doxorubicin, can promote cell death...There are currently two ongoing clinical trials focusing on the activation of DR5, namely, IGM-8444 and INBRX-109, which have progressed to phase 2. Further modifications of TRAIL delivery with fusion to single-chain variable fragments (scFv-TRAIL), directed against tumor-associated antigens (TAAs), and in the use of stem cells focus on targeted TRAIL delivery to cancer cells using bi-functional strategies. In vitro, in vivo, and clinical trials, as well as advances in imaging and theranostics, indicate that targeting DR5 remains a valid strategy in the treatment of some relapsed and refractory cancers."

Journal • Review • Oncology • Osteosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • TNFRSF10B

Press Release: Sanofi completes acquisition of Inhibrx, Inc. (GlobeNewswire) - "Sanofi announced today the completion of its acquisition of Inhibrx, Inc...The acquisition adds SAR447537 (formerly INBRX-101) to Sanofi’s rare disease pipeline, underscoring the company’s commitment to pursuing differentiated and potential best-in-class medicines that build upon our existing strengths and capabilities...The former holders of shares of Inhibrx common stock voted to approve the acquisition at a special meeting of stockholders on May 24, 2024. Upon the closing of the acquisition, former shareholders of Inhibrx became entitled to receive $30.00 per share in cash, which represents a total equity value of approximately $1.7 billion (on a fully diluted basis), as well as one contingent value right per share to receive $5.00 upon the achievement of a regulatory milestone....'Inhibrx Biosciences, which was a wholly owned subsidiary of Inhibrx prior to the distribution, acquired all of the assets of Inhibrx not related to SAR447537, which include INBRX-109 and INBRX-106...'"

M&A • Alpha-1 Antitrypsin Deficiency • Oncology • Rare Diseases • Solid Tumor

Inhibrx Inc. Stockholders Approve Sale of INBRX-101 to Sanofi (PRNewswire) - " Inhibrx...announced that, at a special meeting (the 'Special Meeting'), the Company's stockholders approved the sale to Sanofi of all the assets and liabilities primarily related to INBRX-101, an optimized, recombinant alpha-1 antitrypsin ('AAT') augmentation therapy currently in a registrational trial for the treatment of patients with alpha-1 antitrypsin deficiency ('AATD'). Immediately prior to the closing of the merger, all non-101 assets and liabilities, including INBRX-105, INBRX-106, INBRX-109, Inhibrx's non-101 discovery pipeline and its corporate infrastructure, will be spun out from the Company into a new publicly traded company, Inhibrx Biosciences, Inc. ('New Inhibrx')."

Commercial • Alpha-1 Antitrypsin Deficiency • Solid Tumor

A role for the oncogenic driver fusion protein EWS-FLI1 in the targeting of DR5 by INBRX-109 in Ewing sarcoma (AACR 2024) - "INBRX-109 is an exciting candidate for ES as a single agent in subsets of tumors or in combination with irinotecan, which is currently being evaluated in the clinic. Investigation of the exact relationship between EWS-FLI1 and sensitivity to DR5 targeting is ongoing. Initial findings suggest EWS-FLI1, combined with other disease modifying mutations, is a key mediator of this sensitivity."

Ewing Sarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • EWSR1 • FLI1 • TNFA • TNFRSF10B

Phase 1 Study of INBRX-109 in Subjects With Locally Advanced or Metastatic Solid Tumors Including Sarcomas (clinicaltrials.gov) - P1 | N=240 | Recruiting | Sponsor: Inhibrx, Inc. | Trial completion date: Dec 2024 ➔ Jul 2026 | Trial primary completion date: Aug 2024 ➔ Dec 2025

Metastases • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Ewing Sarcoma • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Sarcoma • Solid Tumor

COMBINATION TREATMENT WITH TEMOZOLOMIDE AND THE DEATH RECEPTOR-5 AGONIST INBRX-109 EFFECTIVELY TARGETS SUCCINATE DEHYDROGENASE -DEFICIENT GASTROINTESTINAL STROMAL TUMOR (CTOS 2023) - P1, P2 | "Herein, we report that SDH-def tumors are sensitive to TMZ, which induces ER stress and upregulates DR5, a pro-apoptotic receptor that can be targeted by INBRX-109 (Figure 1). In turn, TMZ+INBRX-109 additively/synergistically reduces SDH-def GIST cell viability in vitro. These data provide the preclinical evidence for a Phase I clinical trial (3+3 dose escalation design with two dosing cohorts, NCT03715933) to study the safety/tolerability of TMZ+INBRX-109 in patients with aggressive SDH-def cancers, including GIST (Figure 2)."

Stroma • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • ATF4 • CASP3 • SDHA • SDHC • TNFRSF10B

ChonDRAgon: Study of INBRX-109 in Conventional Chondrosarcoma (clinicaltrials.gov) - P2 | N=201 | Recruiting | Sponsor: Inhibrx, Inc. | Trial completion date: Jun 2024 ➔ Jun 2025 | Trial primary completion date: Feb 2024 ➔ Dec 2024

Metastases • Trial completion date • Trial primary completion date • Oncology • Sarcoma • Solid Tumor

Inhibrx Announces Sale of INBRX-101 to Sanofi for an aggregate value of up to $2.2B (PRNewswire) - "Inhibrx, Inc...and Sanofi...today announced that the companies have entered into a definitive agreement under which Aventis Inc., a Pennsylvania corporation (a subsidiary of Sanofi) will acquire all the assets and liabilities associated with INBRX-101, an optimized, recombinant alpha-1 antitrypsin ('AAT') augmentation therapy currently in a registrational trial for the treatment of patients with alpha-1 antitrypsin deficiency ('AATD'). Immediately prior to the closing of the merger, all non-101 assets and liabilities, including INBRX-105, INBRX-106, INBRX-109, Inhibrx's non-101 discovery pipeline and its corporate infrastructure, will be spun out from the Company into a new publicly traded company, Inhibrx Biosciences, Inc. ('New Inhibrx')....New Inhibrx will continue to own Inhibrx's other clinical therapeutic candidates, INBRX-105, INBRX-106, and INBRX-109..."

Commercial • Licensing / partnership • Alpha-1 Antitrypsin Deficiency • Immunology • Oncology • Solid Tumor

Inhibrx Reports Third Quarter 2023 Financial Results and Recent Corporate Highlights (PRNewswire) - "...the Company's payments to its contract research organizations, or CRO, partners continue to increase as the registration-enabling Phase 2 trials progress for both INBRX-101 for the treatment of emphysema due to AATD and INBRX-109 for the treatment of unresectable or metastatic conventional chondrosarcoma, and additional cash outlay to its CRO partners for the INBRX-105 and INBRX-106 Phase 1/2 trials...Research and development expenses were $38.1 million during the third quarter of 2023, compared to $24.9 million during the third quarter of 2022...an increase in clinical trial expenses, primarily related to the registration-enabling Phase 2 trial for INBRX-101 for the treatment of emphysema due to AATD, which was initiated during the current year, as well as the progression of its INBRX-109 registration-enabling Phase 2 trial for the treatment of unresectable or metastatic conventional chondrosarcoma."

Commercial • Alpha-1 Antitrypsin Deficiency • Head and Neck Cancer • Immunology • Oncology • Sarcoma • Solid Tumor

THE TETRAVALENT DEATH RECEPTOR 5 AGONIST INBRX-109 COMBINED WITH CHEMOTHERAPY IN EWING SARCOMA: PRELIMINARY DATA FROM A PHASE 1 STUDY (CTOS 2023) - P1 | "Irinotecan (IRI) and temozolomide (TMZ) are frequently used in the relapsed setting, but prognosis remains poor. INBRX-109+IRI/TMZ led to high response rates in pts with EWS (71%) and DSRCT (33%), with an ORR of 60% in cohort C3; no grade ≥2 hepatotoxicity or significant AEs leading to discontinuation were observed. Our findings support further evaluation of INBRX-109+IRI/TMZ in these tumors. Cohort C3C is now enrolling (n≈10) at the RP2D of 3 mg/kg."

P1 data • Ewing Sarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • TNFRSF10B

Inhibrx Announces Preliminary Data from the Phase 1 Trial of INBRX-109 for the Treatment of Ewing Sarcoma (PRNewswire) - P1 | N=240 | NCT03715933 | Sponsor: Inhibrx, Inc. | "Inhibrx...announced preliminary efficacy and safety data from the Phase 1 trial of INBRX-109 in combination with Irinotecan and Temozolomide (IRI/TMZ) for the treatment of advanced or metastatic, unresectable Ewing sarcoma. Inhibrx presented this dataset as of the data cut of September 8th, 2023 at the Annual Connective Tissue Oncology Society....Among the 13 patients evaluable, which included 7 classical Ewing sarcoma patients (EWS) and 6 round cell sarcoma patients (RCS), the observed disease control rate was 76.9%, or 10 out of 13 patients as measured by RECISTv1.1. There were 7 patients who achieved partial responses (53.8%), 5 of which were observed in classical EWS patients (71.4%) and 2 of which were observed in RCS patients (33.3%). Durable clinical benefit was observed in 4 patients (30.8%) who achieved disease control lasting greater than 6 months."

P1 data • Ewing Sarcoma

Preclinical and Phase 1 Study Results: DR5 Agonist INBRX-109 in Chondrosar. https://bit.ly/3P3SLGW

P1 data

Preclinical Characterization and Phase I Trial Results of INBRX-109, A Third-Generation, Recombinant, Humanized, Death Receptor 5 Agonist Antibody, in Chondrosarcoma (Clin Cancer Res) - P1 | N=240 | NCT03715933 | Sponsor: Inhibrx, Inc. | "In preclinical studies, INBRX-109 led to antitumor activity in vitro and in patient-derived xenograft models, with minimal hepatotoxicity. In the phase I study, INBRX-109 was well tolerated and demonstrated antitumor activity in unresectable/metastatic chondrosarcoma. INBRX-109 led to a disease control rate of 87.1% [27/31; durable clinical benefit, 40.7% (11/27)], including two partial responses, and median PFS of 7.6 months. Most treatment-related adverse events, including liver-related events, were low grade (grade ≥3 events in chondrosarcoma cohorts, 5.7%)."

P1 data • Preclinical • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Study of INBRX-109 in Conventional Chondrosarcoma (clinicaltrials.gov) - P2; N=201; Recruiting; Sponsor: Inhibrx, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Oncology • Sarcoma • Solid Tumor