etakafusp alfa (AB248) / Asher Biotherap - LARVOL DELTA

Asher Bio Announces Clinical Trial Collaboration and Supply Agreement on Etakafusp Alfa (AB248) in Combination with Bispecific T-cell Engager in Patients with Small Cell Lung Cancer (Businesswire) - "Asher Biotherapeutics...announced a clinical trial collaboration and supply agreement with Amgen...to evaluate etakafusp alfa (formerly known as AB248), Asher Bio’s investigational CD8+ T cell targeted interleukin-2 (IL-2) immunotherapy, in combination with IMDELLTRA (tarlatamab), Amgen’s DLL3-targeting Bispecific T-cell Engager (BiTE) therapy, in patients with extensive-stage small cell lung cancer...As part of this collaboration agreement, Amgen will sponsor and operationalize a global Phase 1b study to evaluate the safety and early efficacy of etakafusp alfa in combination with IMDELLTRA in patients with ES-SCLC."

Commercial • Small Cell Lung Cancer

Asher Bio Announces Clinical Supply Agreement to Enable Evaluation of Etakafusp Alfa (AB248) in Combination with Rilvegostomig in a Global Phase 1b/2 Study in Non-Small Cell Lung Cancer (NSCLC) (Businesswire) - "Asher Biotherapeutics...today announced an agreement with AstraZeneca...to supply etakafusp alfa (formerly known as AB248), Asher Bio’s investigational CD8+ T cell targeted interleukin-2 (IL-2) immunotherapy, to be evaluated in combination with rilvegostomig, AstraZeneca’s investigational PD-1/TIGIT immuno-oncology bispecific antibody, in patients with advanced or metastatic NSCLC....As part of this agreement, AstraZeneca will sponsor and operationalize a global study to evaluate the safety and early efficacy of etakafusp alfa as a first-line treatment in combination with rilvegostomig in patients with advanced or metastatic NSCLC. Asher Bio will retain full ownership of etakafusp alfa and will supply AstraZeneca with etakafusp alfa at no cost."

Commercial • New P1/2 trial • Non Small Cell Lung Cancer

CD8 T cell-targeted IL2 demonstrates robust activity, overcomes liver metastasis associated tumor immune tolerance, and rescues anti-PD-1 therapy resistance in dual-tumor immunocompetent murine model (SITC 2024) - "AB248 promote significant clonal expansion of MC38 tumor antigen-specific CD8 T cells and increase of ICOS expression on tumor-specific CD8 T cellsDownload figure Open in new tab Download powerpoint Abstract 814 Figure 5 FACS analysis of CD11b+ cells. AB248 increase in MHC-II, CD80, and CD86 on monocytes, and significant remodeling of the innate immune compartment"

IO biomarker • Preclinical • Liver Cancer • Melanoma • Oncology • Solid Tumor • CD4 • CD8 • CD80 • CD86 • ICOS • IL2 • ITGAM

KEYNOTE-E29: A Study Evaluating AB248 Alone or in Combination With Pembrolizumab in Adult Patients With Solid Tumors (clinicaltrials.gov) - P1 | N=462 | Recruiting | Sponsor: Asher Biotherapeutics, Inc. | N=262 ➔ 462 | Trial completion date: Oct 2025 ➔ May 2027 | Trial primary completion date: Jun 2025 ➔ Aug 2026

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Asher Bio Closes $55 Million Series C Financing to Advance Lead Program into Phase 1b Clinical Trials (Businesswire) - "Asher Biotherapeutics...announced the closing of a Series C financing, which raised $55 million. The financing was led by RA Capital Management, and included new investors AstraZeneca (LSE/STO/Nasdaq: AZN) and Bristol Myers Squibb, along with existing investors Janus Henderson Investors, Third Rock Ventures, Wellington Management and Boxer Capital and other undisclosed institutional investors....Asher Bio plans to use the proceeds from this financing to advance the clinical development of its lead program, AB248, a novel CD8+ T cell selective IL-2, generated by fusing a reduced potency IL-2 mutein to an anti-CD8β antibody."

Financing • Oncology • Solid Tumor

Asher Bio Announces Publications in Cancer Discovery Highlighting the Differentiated Profile of AB248, its CD8+ T Cell Selective IL-2 Product Candidate (Businesswire) - "Asher Biotherapeutics...announced the publication of two manuscripts in Cancer Discovery, a journal of the American Association for Cancer Research, detailing the design of AB248 and reviewing preclinical data supporting its development as a potentially best-in-class interleukin-2 (IL-2) therapy.....In preclinical mouse models, a single dose of AB248’s murine surrogate (CD8-mIL2) demonstrated strongly improved anti-tumor activity and reduced toxicity compared to untargeted not-α IL-2 variants.... Treatment with AB248 broadly armed human intratumoral CD8+ T cells with enhanced effector capacity, specifically enabling reinvigoration of the dysfunctional T cell pool to elicit potent immune activity. Tumor-specific T cells underwent broader and qualitatively superior activation with AB248 treatment compared to programmed death-1 (PD-1) blockade."

Preclinical • Oncology

IL-2 targeted to CD8+ T cells promotes robust effector T cell responses and potent antitumor immunity. (PubMed, Cancer Discov) - "Efficacy was associated with expansion and phenotypic enhancement of tumor-infiltrating CD8+ T cells, including the emergence of a "better effector" population. These data support the potential utility of AB248 in clinical settings."

Journal • Oncology • CD8 • IL2

KEYNOTE-E29: A Study Evaluating AB248 Alone or in Combination With Pembrolizumab in Adult Patients With Solid Tumors (clinicaltrials.gov) - P1 | N=262 | Recruiting | Sponsor: Asher Biotherapeutics, Inc.

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

KEYNOTE-E29: A Study Evaluating AB248 Alone or in Combination With Pembrolizumab in Adult Patients With Solid Tumors (clinicaltrials.gov) - P1 | N=262 | Recruiting | Sponsor: Asher Biotherapeutics, Inc. | Phase classification: P1a/1b ➔ P1

Combination therapy • Metastases • Phase classification • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Asher Bio Presents Promising New Preclinical Data for Cis-targeted Cancer Immunotherapy AB821 at SITC Annual Meeting (Businesswire) - "...at SITC, a poster highlighting Asher Bio’s lead immunotherapy candidate, AB248, a CD8+ T cell-selective IL-2, will be featured in a clinical trial in progress poster. The poster...details the design of the ongoing Phase 1a/1b study of AB248 alone and in combination with pembrolizumab in patients with advanced solid tumors who failed prior standard of care treatments (NCT05653882)."

Clinical protocol • Oncology • Solid Tumor

An open-label, phase 1a/b study of AB248, a CD8+ selective IL-2 mutein fusion protein, alone or in combination with pembrolizumab in patients with advanced solid tumors (AACR 2023) - "Adverse events will be assessed by CTCAE v5.0. The study is currently open for enrollment in the dose escalation phase at multiple sites in the US."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD8 • IL2

Asher Bio to Highlight Pipeline Programs in Presentations at AACR Annual Meeting 2023 (Businesswire) - "Asher Biotherapeutics...announced that the company will present two poster presentations at the American Association for Cancer Research (AACR) Annual Meeting 2023....A poster highlighting Asher Bio’s lead immunotherapy candidate, AB248, a CD8+ T cell-selective IL-2, will be featured as a clinical trial in progress for the ongoing Phase 1a/b study of AB248 alone and in combination with pembrolizumab in patients with advanced solid tumors who failed prior standard of care treatments (NCT05653882). Asher Bio will also present new preclinical data for CAR-T-specific IL-2 and IL-21 therapies demonstrating highly selective delivery of cytokine support to CAR-T cells and enhanced anti-tumor activity via distinct mechanisms."

Preclinical • Trial status • Oncology • Solid Tumor

A Study Evaluating AB248 Alone or in Combination With Pembrolizumab in Adult Patients With Solid Tumors (clinicaltrials.gov) - P1a/1b | N=262 | Recruiting | Sponsor: Asher Biotherapeutics, Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8

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 (Businesswire) - "Asher Biotherapeutics, Inc....announced that the first patient has been dosed with AB248 in a Phase 1 first-in-human study, AB248-101....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)....'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.'"

P1 data • Trial status • Genito-urinary Cancer • Head and Neck Cancer • Kidney Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Study Evaluating AB248 Alone or in Combination With Pembrolizumab in Adult Patients With Solid Tumors (clinicaltrials.gov) - P1a/1b | N=262 | Not yet recruiting | Sponsor: Asher Biotherapeutics, Inc.

Combination therapy • Metastases • New P1 trial • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8

The CD8+ T cell selectivity of AB248 is essential for optimal anti-tumor activity and safety in nonclinical models (SITC 2022) - "CD8+ T cell restriction was essential for optimal anti-tumor activity and safety in nonclinical models. Collectively, this data demonstrates AB248’s differentiation from broadly acting IL-2-based therapies and supports AB248’s clinical development."

Clinical • Oncology • CD8 • IL15 • IL2 • NCAM1

Asher Bio Presents New Preclinical Data at SITC 2022 Further Supporting Advancement of AB248 and AB821 as Highly Differentiated Cis-targeted Cancer Immunotherapies (Businesswire) - "On track to initiate Phase 1 trial of AB248 in 4Q 2022; Plan to file investigational new drug (IND) application for AB821 in 2H 2023...AB248’s murine surrogate, muAB248, delivered strong anti-tumor activity without body weight loss, a general measure of tolerability, while a representative 'not-α' IL-2 could not achieve meaningful activity without body weight loss...Treatment with muAB248 demonstrated expansion of several CD8+ T cell subsets in the mouse tumor immune infiltrate, including stem-like, effector and memory CD8+ T cell subsets, which are distinct from effects of a representative 'not-α' IL-2. In cynomolgus monkeys, repeat doses of AB248 selectively expanded CD8+ T cells by up to 20-fold, and AB248 was generally well-tolerated up to 1 mg/kg, with no adverse histopathology or clinical pathology findings at any dose level."

IND • New P1 trial • Preclinical • Oncology

Asher Bio to Present New Preclinical Data for CD8+ T Cell Targeted Immunotherapies, AB248 and AB821, at SITC 2022 (Businesswire) - "Asher Biotherapeutics, Inc....announced that it will present preclinical data for two of its cis-targeted immunotherapies, AB248 and AB821, at the Society for Immunotherapy in Cancer (SITC) 37th Annual Meeting, being held in Boston, Massachusetts, on November 8-12, 2022...Asher Bio plans to investigate the use of AB248 in multiple solid tumor indications as monotherapy and in combination with PD(L)-1 checkpoint inhibitors and expects to initiate a Phase 1 clinical trial in the fourth quarter of 2022....Asher Bio expects to file an investigational new drug application for AB821 in the second half of 2023."

IND • New P1 trial • Preclinical • Oncology • Solid Tumor

Asher Bio Announces Clinical Trial Collaboration with Merck to Evaluate AB248 in Combination with KEYTRUDA (pembrolizumab) in Patients with Locally Advanced or Metastatic Solid Tumors (Businesswire) - "Asher Biotherapeutics...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."

Licensing / partnership • New P1 trial • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

AB248 is a CD8+ T cell selective IL-2 designed for superior safety and anti-tumor efficacy (AACR 2022) - "Our data suggest that while AB248 can induce antigen-independent expansion of CD8+ T cells, it only induces effector cytokine secretion in the context of an additional activating signal via the TCR. Collectively, these data show that AB248 demonstrates an improved safety and efficacy profile as compared to not-α IL-2 and is a promising immuno-oncology therapeutic."

Clinical • IO biomarker • Oncology • CD8 • IFNG • IL15 • IL2 • NCAM1 • STAT5 • STAT5AWqe

Asher Bio to Present New Preclinical Data Demonstrating Differentiated Profile of AB248, its Lead Cis-targeted IL-2 Immunotherapy, at AACR Annual Meeting (Businesswire) - “AB248 highlights our cis-targeting strategy, which optimizes the use of immunomodulators by selectively focusing their effect to specific immune cell types. By precisely activating only CD8+ T cells, the primary immune cell subset that drives anti-tumor efficacy in response to IL-2 pathway activation, we believe AB248 has the potential to deliver a highly differentiated product profile, that could become a backbone of immuno-oncology treatment across a range of solid tumors.”

Preclinical • Oncology • Solid Tumor

Asher Bio to Showcase Continued Progress with Lead Program AB248 and Growing Pipeline of Precisely-Targeted Immunotherapies at AACR Annual Meeting 2022 (Businesswire) - "Asher Biotherapeutics...today announced plans to present new data for multiple research programs across its portfolio of cis-targeted immunotherapies at the American Association for Cancer Research (AACR) Annual Meeting 2022, being held in New Orleans, Louisiana, April 8-13, 2022....Asher Bio expects to file an investigational new drug application...for AB821, its CD8-targeted IL-21 immunotherapy, in the second half of 2023."

Clinical data • IND • Oncology • Solid Tumor

Asher Bio Announces New Preclinical Data Demonstrating Best-in-Class Potential of AB248, Its Lead Cis-Targeted Il-2 Immunotherapy (Businesswire) - “IND filing for AB248 on-track for 3Q 2022…‘We look forward to advancing AB248 into clinical studies across multiple solid tumor types next year.’…New preclinical data from studies of CD8-IL2...data showed that: In an anti-PD-1 resistant tumor model, a single dose of CD8-IL2 resulted in complete tumor rejection in 90% of treated mice. In contrast, high dose IL-2 produced minimal efficacy. Treatment with CD8-IL2 led to the expansion of antigen specific T cells with increased expression of activation-associated markers and reduced expression of exhaustion-associated markers. CD8-IL2 monotherapy was well-tolerated, demonstrating therapeutic activity without inducing body weight loss....Preclinical in vitro and in vivo data, which showed that: Treatment with a single dose of CD8-IL2 resulted in a majority of complete responses in established MC-38 tumors, and superior efficacy as compared to a “not α” IL-2...."

IND • New trial • Preclinical • Oncology • Solid Tumor

Asher Bio to Present Preclinical Proof-of-Concept Data for AB248, a Highly Selective CD8-targeted IL-2 Therapy, at SITC 2021 (Businesswire) - "Asher Biotherapeutics...announced that it will present two abstracts at the Society for Immunotherapy of Cancer 36th Annual Meeting (SITC 2021), being held in Washington D.C. and virtually, November 10-14, 2021. Collectively, the presentations demonstrate preclinical proof-of-concept for Asher Bio’s cis-targeting approach and lead program AB248. AB248 is an engineered interleukin-2 (IL-2) immunotherapy, designed specifically to target CD8+ effector T cells. Asher expects to file an investigational new drug application for AB248 in the third quarter of 2022."

IND • Preclinical • Oncology • Solid Tumor

Asher Bio Closes $108 Million Series B Financing (Businesswire) - "Asher Biotherapeutics...announced the closing of an oversubscribed Series B financing, which raised $108 million...Proceeds will fund development of AB248, a CD8-targeted IL-2 immunotherapy, through clinical proof-of-concept, as well as advancement of additional cis-targeted product candidates...Asher Bio expects to file an IND application for AB248 with the U.S. Food and Drug Administration in the third quarter of 2022."

Financing • IND • Oncology