SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Asher Biotherapeutics, a biotechnology company developing precisely-targeted immunotherapies for cancer, autoimmune, and infectious diseases, today announced that it has entered into a clinical trial collaboration and supply agreement with Merck (known as MSD outside of the United States and Canada) for a planned Phase 1a/1b dose escalation and expansion trial to evaluate AB248, Asher Bio’s novel investigational CD8-targeted interleukin 2 (IL-2), as a monotherapy and in combination with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with locally advanced or metastatic solid tumors, including melanoma, renal cell carcinoma (RCC), non-small cell lung carcinoma (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). Under the terms of the agreement, Asher Bio is responsible for conducting the Phase 1a/1b trial, which it expects to initiate in the second half of 2022.
Mechanistically, IL-2 signaling is complementary to PD-1 checkpoint blockade: checkpoint inhibitors release the brakes on T cells, allowing them to kill cancer cells, while IL-2 pushes on the gas pedal driving an increase in the number and activity of T cells. In the clinic, there have been studies conducted on high dose IL-2 as a monotherapy to treat PD-1 failures and on high dose IL-2 in combination with PD-1 checkpoint inhibitors in earlier lines of therapy that both demonstrated encouraging activity. However, despite high dose IL-2 efficacy in these settings, severe toxicities significantly hamper use of IL-2 in practice.
Asher Bio previously reported preclinical data from studies of a murine surrogate of AB248, which achieved significant anti-tumor activity as monotherapy and in combination with anti-PD1, without toxicity associated body weight loss. In comparison, treatment with a “not α” IL-2 achieved lower anti-tumor activity and was accompanied by body weight loss.
“We are looking forward to initiating this trial in collaboration with Merck to evaluate AB248 in combination with KEYTRUDA® in a range of cancers,” said Craig Gibbs, Ph.D., Chief Executive Officer of Asher Bio. “Treatment with PD-1 checkpoint blockade monotherapy or in combination with chemotherapy or another immunotherapy has become a recommended first line treatment in multiple indications. Yet for patients who failed to achieve a response or who relapse, treatment options are limited. In addition, there is a subset of first line patients where there is an opportunity to enhance the current standard of care. We believe that by precisely focusing the effect of IL-2 to the primary immune cell subset that drives anti-tumor efficacy, AB248 may have the potential to deliver a highly differentiated product profile that could become a backbone of immuno-oncology across a range of solid tumors.”
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.
AB248 is a novel CD8+ T cell selective IL-2, generated by fusing a reduced potency IL-2 mutein to a humanized IgG1 anti-CD8β antibody. It was specifically engineered to selectively and potently expand 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 some preclinical studies, AB248 exhibits an approximately 1,000-fold preference for the activation of CD8+ T cells over NK cells and Tregs. In other nonclinical studies, AB248 has 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 precisely targeted immunotherapies for cancer and other diseases. Its cis-targeting platform aims to enable selective activation of specific immune cell types, addressing the inherent limitations of otherwise pleiotropic immunotherapies that act on multiple cell types. Its approach has the potential to precisely direct different immune mediators against a range of target immune cell-types and create novel immunotherapies in cancer, autoimmune and infectious diseases. 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 www.asherbio.com and follow us on Twitter @AsherBio and on LinkedIn.