Asher Bio Announces Dosing of First Patient in Phase 1a/1b Clinical Trial of AB248, a Cis-targeted IL-2 Immunotherapy Product Candidate, for the Treatment of Locally Advanced or Metastatic Solid Tumors

-- AB248 is the first candidate from Asher Bio’s portfolio of highly differentiated cis-targeted investigational immunotherapies to enter clinical development --

-- Phase 1 first-in-human study to evaluate AB248 alone or in combination with pembrolizumab, with initial safety, pharmacokinetic and mechanistically important pharmacodynamic readouts anticipated in 2023 --

SOUTH SAN FRANCISCO, CA, USA I January 17, 2023 IAsher Biotherapeutics, Inc. (Asher Bio), a biotechnology company focused on developing therapies to precisely engage specific immune cells to fight cancer, today announced that the first patient has been dosed with AB248 in a Phase 1 first-in-human study, AB248-101. 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), Merck’s anti-PD1 therapy, in patients with recurrent locally advanced or metastatic solid tumors, including melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). As previously announced, Asher Bio is conducting this Phase 1a/1b trial under a clinical trial collaboration and supply agreement with Merck (known as MSD outside the United States and Canada).

“We are delighted to begin clinical evaluation of AB248, our most advanced product candidate,” said Craig Gibbs, Ph.D., Chief Executive Officer of Asher Bio. “This is a significant milestone for Asher Bio and our efforts to deliver a new class of therapies that address the limitations of existing immune-based medicines by specifically targeting them to, and activating, only the desired immune cell type, thereby avoiding pleiotropic effects that can both hinder efficacy and drive toxicity. I am grateful to our research team, which advanced AB248 from ideation through preclinical development in only three years, and I look forward to working with our clinical partners at sites across the United States to evaluate the potential of AB248 to deliver better outcomes – and restore hope, health and happiness – to patients with difficult-to-treat solid tumors.”

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 α) 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 American Association for Cancer Research (AACR) Annual Meeting 2022, where AB248 demonstrated an approximately 1000-fold preference for the activation of CD8+ T cells over NK cells and Tregs.

“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 Dr. Costantine Albany and staff at Horizon Oncology, Lafayette IN for treating the first patient on January 10th, 2023, as well as Dr. David Spigel at Sarah Cannon Research Institute at Tennessee Oncology, Nashville and Dr. Elizabeth Buchbinder at the Dana Faber Cancer Institute and their respective staff for their collaboration as we start our Phase 1 study,” said Andrea Pirzkall, M.D., Chief Medical Officer of Asher Bio. “Our research team designed AB248 to enable improved safety and efficacy by acting only on CD8+ T cells. Preclinical data showed AB248 to have a highly differentiated pharmacodynamic profile relative to other IL-2 therapeutics, suggestive of a potentially best-in-class IL-2 therapy. We expect to know from pharmacodynamic data whether treatment with AB248 is having its desired effect and hope to achieve proof-of-mechanism early in our development effort. We look forward to reporting initial clinical data in the second half of 2023.”

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 Elizabeth Buchbinder, M.D., Dana-Farber Cancer Center and investigator in the Phase 1a/1b clinical trial. “Although there has been significant progress made in the treatment of patients with locally advanced and metastatic solid tumors, many patients remain underserved by existing options, particularly once they have failed therapy with immune checkpoint inhibitors. I am encouraged by the preclinical data supporting AB248’s differentiated profile and look forward to working with Asher Bio and fellow clinical investigators to evaluate AB248 in this Phase 1a/1b clinical trial.”

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA

About AB248
AB248 is a novel CD8+ T cell selective IL-2, generated by fusing a reduced potency IL-2 mutein to an anti-CD8β 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 Ivana Djuretic and Andy Yeung with support from Third Rock Ventures and is located in South San Francisco. For more information, please visit asherbio.com and follow us on Twitter @AsherBio and on LinkedIn.

1 Clinigen Group/Novartis. Proleukin® (aldesleukin) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/103293s5130lbl.pdf. Revised July 2012.
2 Buchbinder EI, Dutcher JP, Daniels GA, et al. Therapy with high-dose Interleukin-2 (HD IL-2) in metastatic melanoma and renal cell carcinoma following PD1 or PDL1 inhibition. J Immunother Cancer. 2019;7(1):49. Published 2019 Feb 18. doi:10.1186/s40425-019-0522-3

SOURCE: Asher Bio

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