AB248, a CD8-targeted interleukin-2 (IL-2), is Asher Bio's lead compound and first to enter the clinic for the treatment of patients with solid tumors. The Phase 1a/1b study, which consists of a dose escalation and expansion stage, will evaluate AB248 as a monotherapy and in combination with KEYTRUDA (pembrolizumab),
We are delighted to begin clinical evaluation of AB248, our most advanced product candidate,' said
High dose IL-2 (aldesleukin, Proleukin) was the first modern immunotherapy to show long lasting, durable, complete responses in a subset of cancer patients, leading to its approval for the treatment of patients with metastatic melanoma and RCC.[1] More recently, high dose IL-2 also demonstrated similar responses in melanoma and RCC patients who previously failed checkpoint inhibitor immunotherapy.[2] However high dose IL-2 has been associated with significant toxicities limiting its clinical use, and newer second-generation (not) IL-2 medicines are generally limited by off-target effects that both suppress anti-tumor responses and drive toxicity. In order to overcome these challenges, Asher Bio developed an innovative cis-targeting approach to deliver IL-2 only to a specific immune cell subset. AB248 is an investigational cis-targeted immunotherapy that was engineered to selectively activate CD8+ T cells, which drive anti-tumor efficacy, while avoiding NK cells, which can act as a pharmacological sink and contribute to toxicity, as well as avoiding Tregs, which are immunosuppressive. Preclinical data were presented at the
We are very excited to enter the clinical evaluation of AB248 to assess its therapeutic potential in patients who failed prior standard of care treatments, and are very thankful to
About AB248 Phase 1 Trial
AB248-101 is an open-label Phase 1a/b study consisting of a dose escalation and expansion phase to investigate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of AB248 alone and in combination with pembrolizumab in subjects with locally advanced/metastatic solid tumors who failed prior therapies. The dose escalation phase will follow the Bayesian Optimal Interval (BOIN) design and enroll subjects at multiple dose levels and frequencies for the AB248 monotherapy portion and pembrolizumab combination.
Upon determining a recommended dosing regimen, the study will open indication specific expansion cohorts to further evaluate monotherapy AB248 and the combination of AB248 and KEYTRUDA in patients with melanoma, RCC and NSCLC after failure to prior therapies, as well as first-line SCCHN. Please refer to www.clincialtrials.gov (NCT05653882) for additional details related to this Phase 1a/1b clinical trial.
I am excited to begin administering AB248 to patients as part of this clinical trial,' said
KEYTRUDA is a registered trademark of
About AB248
AB248 is a novel CD8+ T cell selective IL-2, generated by fusing a reduced potency IL-2 mutein to an anti-CD8 antibody. It was specifically engineered to selectively and potently activate CD8+ T-cells, while avoiding natural killer (NK) cells, which can act as a pharmacological sink and contribute to toxicity, and regulatory T (Treg) cells, which are immunosuppressive. In preclinical studies, AB248 exhibited an approximately 1,000-fold preference for the activation of CD8+ T cells over NK cells and Tregs. In preclinical murine tumor studies, AB248 demonstrated potent anti-tumor activity both alone and in combination with PD-1 checkpoint blockade in a wide variety of murine tumor models.
About Asher Bio
Asher Bio is a biotechnology company developing therapies to precisely engage specific immune cells to fight cancer, chronic viral infection and autoimmune disease. We utilize our proprietary cis-targeting platform to develop therapies engineered to overcome limitations of other immune-based treatments by selectively activating specific immune cell types with validated disease fighting functionality. Our candidates feature an antibody connected to a modified immunomodulatory protein, such as a cytokine. Our candidate design is intended to enable our candidates to selectively activate the desired immune cells and not other cells that contribute to toxicity or immune suppression. Asher Bio was founded by
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