On March 5, 2024 TME Pharma N.V. (Euronext Growth Paris: ALTME), a biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported that the US Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND)1 application for NOX-A12, TME Pharma’s CXCL12 inhibitor, for use in the treatment of aggressive adult brain cancer, glioblastoma (Press release, TME Pharma, MAR 5, 2024, View Source [SID1234640841]).

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With the IND now open at the FDA, TME Pharma plans to proceed with the continued clinical development of NOX-A12 in a Phase 2 randomized controlled study in approximately 100 newly diagnosed, chemotherapy-resistant glioblastoma patients having residual measurable tumor remaining after surgery. The study is expected to be initiated later this year, starting first in Europe, once the necessary resources and preparations are in place. Sufficient NOX-A12 clinical grade material has already been manufactured to initiate the study.

"Receiving approval of the FDA for the design of our Phase 2 clinical trial in glioblastoma provides a clear roadmap to potential industrial partners and investors on the next steps in clinical development. The discussions with the FDA have been constructive and have allowed us to design a robust Phase 2 that should provide us with solid evidence of the highly differentiated profile of NOX-A12 in combination with bevacizumab in newly diagnosed, chemotherapy-resistant glioblastoma patients. The open IND will also allow us to expand our clinical development into the US, where we expect to generate significant interest in the medical community," said Aram Mangasarian, CEO of TME Pharma. "We also expect to receive the FDA’s decision regarding Fast-Track Designation for NOX-A12 in glioblastoma in the next few weeks, which can further strengthen our regulatory position in the US and should help us in the search for industrial and financial partners who can assist TME Pharma in bringing NOX-A12 to patients in the quickest way possible."

The study will address questions of dosing and contribution of components – NOX-A12 and bevacizumab – to overall efficacy of the combination therapy and will allow TME Pharma to optimize late phase development by testing multiple doses of NOX-A12 with bevacizumab in a patient population that is also randomized to standard of care. Together with the IND submission TME Pharma has also submitted a Fast-Track Designation2 request to the FDA to secure an expedited regulatory pathway for NOX-A12 in glioblastoma and the company expects to receive the FDA’s decision before the end of March 2024.

Based on discussions with the FDA last year and further interaction during the IND application process, the FDA-approved study design includes five arms, with 20 patients per arm:

Arm 1: NOX-A12 – 200mg/week + radiotherapy and bevacizumab
Arm 2: NOX-A12 – 400mg/week + radiotherapy and bevacizumab
Arm 3: NOX-A12 – 600mg/week + radiotherapy and bevacizumab
Arm 4: NOX-A12 – 600mg/week + radiotherapy
Arm 5: Standard of Care control (temozolomide + radiotherapy)
TME Pharma’s regulatory interactions were supported by recent survival data from the GLORIA Phase 1/2 study in which NOX-A12 demonstrated an unprecedented median Overall Survival (mOS) of 19.9 months in combination with bevacizumab and radiotherapy in glioblastoma patients with measurable chemotherapy-resistant residual tumors after surgery. This survival rate compares very favorably to a matched standard of care reference cohort, which achieved an mOS of approx. 10 months, and exceeds what TME Pharma believes to be all relevant competitor therapy trials in newly diagnosed glioblastoma patients resistant to standard chemotherapy.

On March 5, 2024 Ankyra Therapeutics, a clinical stage biotechnology company pioneering anchored immunotherapies to treat cancer, reported the first patient dosed in the dose escalation cohort in a Phase 1 clinical study evaluating ANK-101, a tumor-directed, anchored immune medicine for solid tumors (Press release, Ankyra Therapeutics, MAR 5, 2024, View Source [SID1234640840]).

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"The first patient dosed in the Phase 1 monotherapy study of ANK-101 marks a significant milestone in our mission to provide a potential treatment to patients with minimal unwanted side effects," said Howard L. Kaufman, M.D., President and Chief Executive Officer of Ankyra Therapeutics. "This is not only a critical step in the development of our first-in-class asset, ANK-101, but also in our ultimate commitment to bring other biologically active agents as anchored immunotherapies to those who need them most."

ANK-101, an interleukin-12 (IL-12) cytokine anchored to aluminum hydroxide, is locally delivered and retained in the tumor microenvironment for several weeks where it mediates recruitment and activation of effector immune cells. ANK-101 is currently under investigation in patients with advanced solid tumors who have failed standard of care treatments. In multiple preclinical models, ANK-101 demonstrated increased immune cell infiltration into tumors without systemic toxicity.

The dose escalation cohort portion of the study will assess the safety of ANK-101 and determine the recommended dose for expansion in people with cutaneous, subcutaneous, soft tissue, or nodal malignancies, with an additional 10 participants ultimately dosed at the recommended dose for expansion (RDE). The study will secondarily evaluate the PK, immunogenicity, and preliminary clinical activity of the medicine.

"These data will provide a roadmap for advancing ANK-101 through clinical development and for identifying appropriate clinical indications for future trials," said Joe Elassal, M.D., MBA, Chief Medical Officer of Ankyra Therapeutics. "We believe this approach will enable patients to receive effective immunotherapy while potentially mitigating significant side effects during treatment."

"ANK-101 capitalizes on a novel delivery mechanism, and this anchored immune medicine approach to oncology represents potential for positive impact across indications," said Jong Chul Park M.D., assistant professor at Harvard Medical School and attending physician at Mass General Cancer Center, an investigator of the Phase 1 dose escalation trial. "Patient wellbeing throughout the treatment journey is paramount, and I look forward to our ongoing work together."

About ANK-101
ANK-101 is an anchored drug complex composed of interleukin-12 (IL-12) linked to aluminum hydroxide. ANK-101 enables local delivery of functional IL-12 to the tumor microenvironment where it remains biologically active for several weeks but does not diffuse into the systemic circulation, thereby avoiding systemic toxicity. Treatment with ANK-101 in animal models has been associated with recruitment and retention of CD8+ T cells, NK cells and M1 macrophages activating innate and adaptive anti-tumor immunity. ANK-101 is being evaluated for the treatment of advanced solid tumors alone and in combination with anti-PD-1 agents. The Phase 1 first-in-human, open-label clinical trial of ANK-101 as a monotherapy (NCT:06171750) consists of a dose escalation portion that will evaluate the safety and tolerability of ANK-101, followed by dose expansion cohorts.

On March 5, 2024 Ankyra Therapeutics, a clinical stage biotechnology company pioneering anchored immunotherapies to treat cancer, reported the first patient dosed in the dose escalation cohort in a Phase 1 clinical study evaluating ANK-101, a tumor-directed, anchored immune medicine for solid tumors (Press release, Ankyra Therapeutics, MAR 5, 2024, View Source [SID1234640840]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The first patient dosed in the Phase 1 monotherapy study of ANK-101 marks a significant milestone in our mission to provide a potential treatment to patients with minimal unwanted side effects," said Howard L. Kaufman, M.D., President and Chief Executive Officer of Ankyra Therapeutics. "This is not only a critical step in the development of our first-in-class asset, ANK-101, but also in our ultimate commitment to bring other biologically active agents as anchored immunotherapies to those who need them most."

ANK-101, an interleukin-12 (IL-12) cytokine anchored to aluminum hydroxide, is locally delivered and retained in the tumor microenvironment for several weeks where it mediates recruitment and activation of effector immune cells. ANK-101 is currently under investigation in patients with advanced solid tumors who have failed standard of care treatments. In multiple preclinical models, ANK-101 demonstrated increased immune cell infiltration into tumors without systemic toxicity.

The dose escalation cohort portion of the study will assess the safety of ANK-101 and determine the recommended dose for expansion in people with cutaneous, subcutaneous, soft tissue, or nodal malignancies, with an additional 10 participants ultimately dosed at the recommended dose for expansion (RDE). The study will secondarily evaluate the PK, immunogenicity, and preliminary clinical activity of the medicine.

"These data will provide a roadmap for advancing ANK-101 through clinical development and for identifying appropriate clinical indications for future trials," said Joe Elassal, M.D., MBA, Chief Medical Officer of Ankyra Therapeutics. "We believe this approach will enable patients to receive effective immunotherapy while potentially mitigating significant side effects during treatment."

"ANK-101 capitalizes on a novel delivery mechanism, and this anchored immune medicine approach to oncology represents potential for positive impact across indications," said Jong Chul Park M.D., assistant professor at Harvard Medical School and attending physician at Mass General Cancer Center, an investigator of the Phase 1 dose escalation trial. "Patient wellbeing throughout the treatment journey is paramount, and I look forward to our ongoing work together."

About ANK-101
ANK-101 is an anchored drug complex composed of interleukin-12 (IL-12) linked to aluminum hydroxide. ANK-101 enables local delivery of functional IL-12 to the tumor microenvironment where it remains biologically active for several weeks but does not diffuse into the systemic circulation, thereby avoiding systemic toxicity. Treatment with ANK-101 in animal models has been associated with recruitment and retention of CD8+ T cells, NK cells and M1 macrophages activating innate and adaptive anti-tumor immunity. ANK-101 is being evaluated for the treatment of advanced solid tumors alone and in combination with anti-PD-1 agents. The Phase 1 first-in-human, open-label clinical trial of ANK-101 as a monotherapy (NCT:06171750) consists of a dose escalation portion that will evaluate the safety and tolerability of ANK-101, followed by dose expansion cohorts.

On March 5, 2024 AbCellera (Nasdaq: ABCL) reported that its scientists will present four posters with data from its T-cell engager programs and platform at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024, to be held April 5 to 10 at the San Diego Convention Center (Press release, AbCellera, MAR 5, 2024, View Source [SID1234640839]).

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With its T-cell engager platform, AbCellera is expanding therapeutic opportunities for this modality by generating molecules with the potential for improved efficacy and safety profiles for solid tumors and challenging targets such as peptide-MHCs.

AbCellera will present four posters at AACR (Free AACR Whitepaper) that demonstrate how it is leveraging its platform to develop T-cell engagers with potent tumor-cell killing and low cytokine release for multiple cancer targets. Using data integrated from across these programs, AbCellera will present new insights into T-cell engager function. In addition, AbCellera will present data on novel CD28-binding antibodies that can be used to optimize T-cell engagers, particularly for solid tumors that are difficult to treat using current immunotherapies.

Details on AbCellera’s poster presentations at AACR (Free AACR Whitepaper) are as follows:

Title: Functional and specific T-cell engagers against a peptide-MHC tumor target
Abstract Number: 2373
Session: Antibodies 1
Date and Time: Monday, April 8, 2024, 9:00 a.m. to 12:30 p.m. PT
Location: Section 38, Board 19

Title: Diverse CD28-binding IgG and heavy chain-only antibodies for T-cell engager development
Abstract Number: 1859
Session: Antibody-Based Technologies and New Inhibitors
Date and Time: Monday, April 8, 2024, 9:00 a.m. to 12:30 p.m. PT
Location: Section 22, Board 3

Title: Target-dependent considerations for the design of bispecific T-cell engagers
Abstract Number: 1868
Session: Antibody-Based Technologies and New Inhibitors
Date and Time: Monday, April 8, 2024, 9:00 a.m. to 12:30 p.m. PT
Location: Section 22, Board 12

Title: Development of PSMA x CD3 T-cell engagers using an integrated, functional approach
Abstract Number: 6359
Session: Antibodies 2
Date and Time: Tuesday, April 9, 2024, 1:30 p.m. to 5:00 p.m. PT
Location: Section 41, Board 20

About AbCellera’s T-Cell Engager Platform

CD3 T-cell engagers are bispecific antibodies that guide the immune system to find and eliminate cancer cells by binding both cancer-killing T cells and tumor targets at the same time. Developing effective T-cell engagers requires two parental antibodies—a CD3-binding arm that fine-tunes T-cell activation and a tumor-binding arm with high specificity for cancer cells. The small number of available CD3-binding antibodies that can effectively fine-tune T-cell responses has been a barrier to T-cell engager development. To address this barrier, AbCellera developed a complete T-cell engager platform that includes fully human, developable CD3-binding antibodies with unique binding and functional properties. By combining these antibodies with OrthoMab, its clinically validated multispecific engineering platform, and its antibody discovery and development engine, AbCellera’s T-cell engager platform is designed to bring new cancer medicines to the clinic faster.

On March 5, 2024 Boundless Bio, a clinical-stage, next-generation precision oncology company interrogating extrachromosomal DNA (ecDNA) biology to deliver transformative therapies to patients with previously intractable oncogene amplified cancers, reported multiple upcoming poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024, which is being held April 5-10, 2024, in San Diego, CA (Press release, Boundless Bio, MAR 5, 2024, View Source [SID1234640837]).

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Details of the presentations are as follows:

Title: Oral CHK1 inhibitor BBI-355 allows flexibility of dose and schedule with demonstration of monotherapy and combinational antitumor activity in extrachromosomal DNA (ecDNA) driven preclinical models
Abstract Number: 613
Session Category: Experimental and Molecular Therapeutics
Session Title: Kinase and Phosphatase Inhibitors 1
Session Date and Time: Sunday Apr 7, 2024, 1:30 PM – 5:00 PM PT
Location: Poster Section 25
Poster Board Number: 23

Title: Preclinical and clinical pharmacodynamic characterization of BBI-355, a novel, orally bioavailable, and selective CHK1 inhibitor being evaluated in the first-in-human Phase 1/2 POTENTIATE clinical trial of patients with cancer harboring oncogene amplifications
Abstract Number: 3631
Session Category: Clinical Research
Session Title: Biomarkers in Clinical Trials
Session Date and Time: Monday Apr 8, 2024, 1:30 PM – 5:00 PM PT
Location: Poster Section 40
Poster Board Number: 9

Title: ecDNA-based amplification of multi-drug resistance genes leads to acquired resistance to taxane-based chemotherapy
Abstract Number: 5870
Session Category: Experimental and Molecular Therapeutics
Session Title: Mechanisms of Drug Resistance 3
Session Date and Time: Tuesday Apr 9, 2024, 1:30 PM – 5:00 PM PT
Location: Poster Section 24
Poster Board Number: 14

About BBI-355
Boundless Bio’s lead ecDNA-directed therapy (ecDTx), BBI-355, is a novel, oral, selective inhibitor of checkpoint kinase 1 (CHK1) being studied in the ongoing, first-in-human, Phase 1/2 POTENTIATE clinical trial (NCT05827614) in patients with oncogene amplified cancers. CHK1 is a master regulator of cells’ response to replication stress (RS). RS is elevated in ecDNA-enabled oncogene amplified cancer cells and, because of this, represents a key vulnerability of those cells. BBI-355 was designed to exploit the elevated RS in ecDNA-enabled oncogene amplified cancer cells by disrupting proper CHK1 function in regulating RS and thereby facilitating catastrophic RS to preferentially kill cancer cells relative to healthy cells.