A2 Bio Announces First Patient Dosed in DENALI-1 Phase 1/2 Clinical Study of A2B395, a Novel Allogeneic Precision CAR T Cell Therapy for Patients with Solid Tumors that Express EGFR
AGOURA HILLS, Calif.--(BUSINESS WIRE)--A2 Biotherapeutics, Inc. (A2 Bio), a clinical-stage cell therapy company developing first-in-class logic-gated cell therapies for solid tumors, today announced dosing of the first patient in the DENALI-1 (NCT06682793) clinical study. DENALI-1 is a multicenter phase 1/2 dose-escalation clinical study to evaluate the safety and efficacy of A2B395, an allogeneic logic-gated CAR T cell therapy, in participants with solid tumors that express EGFR and have lost HLA-A*02 expression. A2B395 is the first allogeneic therapy utilizing the A2 Bio Tmod™ technology platform to advance into clinical development.
'Dosing of the first patient in DENALI-1 is a key milestone toward providing a precise, novel 'off the shelf' CAR T cell therapy for patients with solid tumors that express EGFR. No curative therapies are available for people living with these cancers."
Share
A2 Bio is advancing A2B395 as a potential new precision cell therapy in participants with solid tumors that express EGFR, including colorectal cancer, non-small cell lung cancer, head and neck squamous cell carcinoma, triple-negative breast cancer, and renal cell carcinoma.
'Dosing of the first patient in DENALI-1 is a key milestone toward providing a precise, novel 'off the shelf' CAR T cell therapy for patients with solid tumors that express EGFR. No curative therapies are available for people living with these cancers, and current treatments can be toxic, debilitating, and fatal. All of us at A2 Bio are grateful to the patients, investigators, and clinical care providers participating in DENALI-1,' said John Welch, M.D., Ph.D, interim chief medical officer of A2 Bio.
Significant unmet needs remain for people living with EGFR-positive cancers, despite recent advances that have produced new targeted therapies, antibody-based therapies, and immunotherapies. 1,2 In the recurrent unresectable, locally advanced, or metastatic setting, the intent of standard of care treatment is typically palliative rather than curative, and has not changed significantly in several decades.
Precision medicine enables efficient identification of patients in the A2 Bio clinical studies. Patients are enrolled in DENALI-1 through BASECAMP-1 (NCT04981119), a master prescreening study that identifies patients with HLA loss of heterozygosity (LOH) at any time in the course of their disease via next-generation sequencing. Upon disease progression, the participant may screen for enrollment in DENALI-1. There is no time requirement between the studies, and patients may go directly from BASECAMP-1 to DENALI-1 based on their own disease course. BASECAMP-1 utilizes artificial intelligence (AI)-enabled precision diagnostics as a cost-effective, high-yield approach to identify eligible patients for all A2 Bio clinical studies. 3, 4
In addition to A2B395, A2 Bio continues to advance its clinical development of A2B694, the BASECAMP-1 prescreening study, as well as other preclinical programs as the company pursues additional pipeline expansion opportunities using its proprietary Tmod™ technology platform. The Tmod™ platform comprises a suite of technologies that can be used in isolation or in combination, and in both autologous and allogeneic settings, to create novel therapies for various cancers and beyond.
The Tmod™ platform utilizes a dual-receptor design consisting of an activator that targets tumor cells and a blocker that protects normal cells. This dual-receptor design is intended to provide selective killing of tumor tissues that express EGFR and have lost the HLA-A*02 gene permanently. This novel design is aimed at tackling the fundamental challenge in solid tumor cancer medicines – the ability to selectively kill tumor cells and protect normal cells.
About DENALI-1
DENALI-1 (NCT06682793) is a phase 1/2, open-label, nonrandomized study evaluating the safety and efficacy of A2B395 in adults. Patients are enrolled through BASECAMP-1 (NCT04981119), a master prescreening study that identifies patients with HLA LOH at any time in the course of their disease via next-generation sequencing. Upon disease progression the participant may screen for enrollment in DENALI-1.
More information about DENALI-1 and clinical trial sites participating in the study are available on the A2 Bio clinical trials website.
About the Tmod™ Platform
A2 Bio has pioneered a precision-targeting cellular system – the Tmod™ platform – that incorporates two receptors, an activator and a blocker, to aim the powerful armaments of immune cells directly at tumors to unequivocally differentiate tumors from normal tissues. The activator recognizes antigens on tumor cells that trigger their destruction, while the blocker recognizes antigens on normal cells that protect them. This novel blocker technology enables precise, personalized and effective T cell targeting. The blocker component equips Tmod™ cells with the capacity to identify tumors as distinct from normal cells.
About A2 Bio
A2 Biotherapeutics, Inc. (A2 Bio) is a clinical-stage biotech company developing first-in-class logic-gated cell therapies to address the high unmet need in cancers. A2 Bio invented the proprietary Tmod™ cell therapy platform to tackle the fundamental challenge in cancer treatment—the ability of cancer medicines to distinguish between tumor and normal cells. For more information, please visit the company's website at www.a2bio.com.
References:
1 Macdonald JB, Macdonald B, Golitz LE, et al. Cutaneous adverse effects of targeted therapies: Part I: Inhibitors of the cellular membrane. J Am Acad Dermatol. 2015;72(2):203-18; quiz 19-20.
2 Ganesh K, Massagué J. Targeting metastatic cancer. Nat Med. 2021;27(1):34-44.
3 Smith CJ, Simeone DM, Grierson PM, et al. Improving ethnic and racial diversity in biomarker-driven clinical trials: a proof of concept with the BASECAMP-1 master prescreening study of patients with high-risk solid tumors with human leukocyte antigen-A*02 (HLA-A*02) loss of heterozygosity (LOH). ASCO Annual Meeting 2024. Available at: https://www.a2bio.com/wp-content/uploads/ASCO-2024_Improving-Trial-Diversity.pdf.
4 Lozac'hmeur A, Danek T, Yang Q, et al. Detecting HLA loss of heterozygosity within a standard diagnostic sequencing workflow for prognostic and therapeutic opportunities. NPJ Precis Oncol. 2024;8(1):174.
Hashtags
Try Our AI Features
Explore what Daily8 AI can do for you:
Comments
No comments yet...
Related Articles
Politico
an hour ago
- Politico
Trump threatens Tillis with primary challenge
Senate Republicans released updated megabill text late Friday that would make sharp cuts to the Inflation Reduction Act's solar and wind tax credits after a late-stage push by President Donald Trump to crack down further on the incentives. The text would require solar and wind generation projects seeking to qualify for the law's clean electricity production and investment tax credits to be placed in service by the end of 2027 — significantly more restrictive than an earlier proposal by the Senate Finance Committee that tied eligibility to when a project begins construction. The changes came after Trump urged Senate Majority Leader John Thune to crack down on the wind and solar credits and align the measure more closely with reconciliation text, H.R.1, that passed the House, as POLITICO reported earlier on Friday. The changes are likely to put some moderate GOP senators, who have backed a slower schedule for sunsetting those incentives, in a tough position. They'll be forced to choose between rejecting Trump's agenda or allowing the gutting of tax credits that could lead to canceled projects and job losses in their states — something renewable energy advocates are also warning about. 'We are literally going to have not enough electricity because Trump is killing solar. It's that serious,' Sen. Brian Schatz (D-Hawaii) responded on X early Saturday. 'We need a bunch of new power on the grid, and nothing is as available as solar. Everything else takes a while. Meantime, expect shortages and high prices. Stupid.' The revised text would retain the investment and production tax credits for baseload sources, such as nuclear, geothermal, hydropower or energy storage, as proposed in the Finance Committee's earlier proposal. But it would make other significant changes, including extending a tax credit for clean hydrogen production until 2028. The panel's earlier proposal would have eliminated the credit after this year. And despite vocal lobbying by the solar industry, the proposal would maintain an abrupt cut to the tax incentive supporting residential solar power. The committee's earlier proposal would have eliminated that credit six months after the enactment of the bill; now the updated draft proposes repealing it at the end of this year. It would also deny certain wind and solar leasing arrangements from accessing the climate law's clean electricity investment and production tax credits, but, in a notable change, removed earlier language specifically disallowing rooftop solar. And it would move up the timeline for certain rules barring foreign entities of concern from accessing those credits. The bill would move up the termination date for electric vehicle tax credits to Sept. 30, compared to six months after enactment in the earlier Finance text. The credit for EV chargers would extend through June 2026. The new text also provides a bonus incentive for advanced nuclear facilities built in communities with high levels of employment in the nuclear industry. And the bill makes metallurgical coal eligible for the advanced manufacturing production tax credit through 2029. Sam Ricketts, co-founder of S2 Strategies, a clean energy policy consulting group, said the new draft is going to 'screw' ratepayers, kill jobs and undermine U.S. economic competitiveness. 'All just to give fossil fuel executives more profits,' he said. 'Or to own the libs. Insanity.' Josh Siegel contributed to this report.
Politico
an hour ago
- Politico
Lee backs down from public land sales push
Senate Republicans released updated megabill text late Friday that would make sharp cuts to the Inflation Reduction Act's solar and wind tax credits after a late-stage push by President Donald Trump to crack down further on the incentives. The text would require solar and wind generation projects seeking to qualify for the law's clean electricity production and investment tax credits to be placed in service by the end of 2027 — significantly more restrictive than an earlier proposal by the Senate Finance Committee that tied eligibility to when a project begins construction. The changes came after Trump urged Senate Majority Leader John Thune to crack down on the wind and solar credits and align the measure more closely with reconciliation text, H.R.1, that passed the House, as POLITICO reported earlier on Friday. The changes are likely to put some moderate GOP senators, who have backed a slower schedule for sunsetting those incentives, in a tough position. They'll be forced to choose between rejecting Trump's agenda or allowing the gutting of tax credits that could lead to canceled projects and job losses in their states — something renewable energy advocates are also warning about. 'We are literally going to have not enough electricity because Trump is killing solar. It's that serious,' Sen. Brian Schatz (D-Hawaii) responded on X early Saturday. 'We need a bunch of new power on the grid, and nothing is as available as solar. Everything else takes a while. Meantime, expect shortages and high prices. Stupid.' The revised text would retain the investment and production tax credits for baseload sources, such as nuclear, geothermal, hydropower or energy storage, as proposed in the Finance Committee's earlier proposal. But it would make other significant changes, including extending a tax credit for clean hydrogen production until 2028. The panel's earlier proposal would have eliminated the credit after this year. And despite vocal lobbying by the solar industry, the proposal would maintain an abrupt cut to the tax incentive supporting residential solar power. The committee's earlier proposal would have eliminated that credit six months after the enactment of the bill; now the updated draft proposes repealing it at the end of this year. It would also deny certain wind and solar leasing arrangements from accessing the climate law's clean electricity investment and production tax credits, but, in a notable change, removed earlier language specifically disallowing rooftop solar. And it would move up the timeline for certain rules barring foreign entities of concern from accessing those credits. The bill would move up the termination date for electric vehicle tax credits to Sept. 30, compared to six months after enactment in the earlier Finance text. The credit for EV chargers would extend through June 2026. The new text also provides a bonus incentive for advanced nuclear facilities built in communities with high levels of employment in the nuclear industry. And the bill makes metallurgical coal eligible for the advanced manufacturing production tax credit through 2029. Sam Ricketts, co-founder of S2 Strategies, a clean energy policy consulting group, said the new draft is going to 'screw' ratepayers, kill jobs and undermine U.S. economic competitiveness. 'All just to give fossil fuel executives more profits,' he said. 'Or to own the libs. Insanity.' Josh Siegel contributed to this report.
Politico
2 hours ago
- Politico
Senate Republicans' tax cuts now projected to cost $4.45T
Senate Republicans released updated megabill text late Friday that would make sharp cuts to the Inflation Reduction Act's solar and wind tax credits after a late-stage push by President Donald Trump to crack down further on the incentives. The text would require solar and wind generation projects seeking to qualify for the law's clean electricity production and investment tax credits to be placed in service by the end of 2027 — significantly more restrictive than an earlier proposal by the Senate Finance Committee that tied eligibility to when a project begins construction. The changes came after Trump urged Senate Majority Leader John Thune to crack down on the wind and solar credits and align the measure more closely with reconciliation text, H.R.1, that passed the House, as POLITICO reported earlier on Friday. The changes are likely to put some moderate GOP senators, who have backed a slower schedule for sunsetting those incentives, in a tough position. They'll be forced to choose between rejecting Trump's agenda or allowing the gutting of tax credits that could lead to canceled projects and job losses in their states — something renewable energy advocates are also warning about. 'We are literally going to have not enough electricity because Trump is killing solar. It's that serious,' Sen. Brian Schatz (D-Hawaii) responded on X early Saturday. 'We need a bunch of new power on the grid, and nothing is as available as solar. Everything else takes a while. Meantime, expect shortages and high prices. Stupid.' The revised text would retain the investment and production tax credits for baseload sources, such as nuclear, geothermal, hydropower or energy storage, as proposed in the Finance Committee's earlier proposal. But it would make other significant changes, including extending a tax credit for clean hydrogen production until 2028. The panel's earlier proposal would have eliminated the credit after this year. And despite vocal lobbying by the solar industry, the proposal would maintain an abrupt cut to the tax incentive supporting residential solar power. The committee's earlier proposal would have eliminated that credit six months after the enactment of the bill; now the updated draft proposes repealing it at the end of this year. It would also deny certain wind and solar leasing arrangements from accessing the climate law's clean electricity investment and production tax credits, but, in a notable change, removed earlier language specifically disallowing rooftop solar. And it would move up the timeline for certain rules barring foreign entities of concern from accessing those credits. The bill would move up the termination date for electric vehicle tax credits to Sept. 30, compared to six months after enactment in the earlier Finance text. The credit for EV chargers would extend through June 2026. The new text also provides a bonus incentive for advanced nuclear facilities built in communities with high levels of employment in the nuclear industry. And the bill makes metallurgical coal eligible for the advanced manufacturing production tax credit through 2029. Sam Ricketts, co-founder of S2 Strategies, a clean energy policy consulting group, said the new draft is going to 'screw' ratepayers, kill jobs and undermine U.S. economic competitiveness. 'All just to give fossil fuel executives more profits,' he said. 'Or to own the libs. Insanity.' Josh Siegel contributed to this report.
