To Physicians

ACEA Therapeutics is committed to developing and delivering novel medicines designed to improve the lives of patients with life-threatening diseases.

Abivertinib

Abivertinib, discovered by ACEA Therapeutics (a subsidiary of Sorrento Therapeutics), is a dual inhibitor of the epidermal growth factor receptor (EGFR) and Bruton’s Tyrosine Kinase (BTK) receptor.

As a third-generation EGFR inhibitor for NSCLC, Abivertinib has three advantages: the inhibition of T790M isoform-specific kinase activity, maintaining efficacy against exon 19 and 21 mutations, and sparing the wild-type EGFR. More than 600 patients have been treated with Abivertinib at different doses. Positive clinical efficacy and manageable adverse events in 300 patients with EGFR T790M+ NSCLC as a second line therapy was reported in Clinical Cancer Research. Abivertinib showed similar efficacy to Osimertinib (Tagrisso), an only FDA approved third generation EGFR inhibitor, but a different resistant mechanism, warranting a potential of alternative use in NSCLC. Recently FDA granted IND clearance for Phase II clinical trial to treat Tagrisso resistant patients, a pivotal study potentially leading to the drug approval based on the communication with FDA.

Abivertinib is also a potent irreversible inhibitor of BTK which is a critical molecule in B cell development and signaling. Abivertinib has completed an open-label Phase Ib study in patients with R/R B-cell lymphoma (NCT03060850) in China. Favorable safety and tolerability with encouraging clinical efficacy in patients with R/R B-cell malignancies, a Phase II registration trial with a subtype B-cell lymphoma will be soon initiated in China.

BTK is also a critical molecule in immune regulation and host inflammatory responses. Abiveritinib showed potent anti-inflammation and immune modulation activities by inhibiting production of key pro-inflammatory cytokines including IL-1beta, IL-6, and TNF-alpha. These cytokines are associated with cytokine release syndrome (CRS) and COVID-19 disease progression with poor outcomes in patients with acute respiratory distress syndrome (ARDS). The trial, titled A Phase 2, Double Blinded, Randomized Study of the Efficacy and Safety of STI-5656 (Abivertinib Maleate) With Standard of Care Versus Standard of Care in Subjects Hospitalized With COVID-19 (NCT04440007), has been completed in USA and Brazil.

Olgotrelvir

Olgotrelvir is discovered and developed by ACEA Therapeutics (a subsidiary of Sorrento Therapeutics). It is the first clinical stage dual inhibitor of coronavirus main protease (Mpro) and human cell cathepsin (Cathepsin L), which can effectively inhibit both SARS-CoV-2 replication and entry into host cells.

Olgotrelvir displays potent antiviral activity against multiple SARS-CoV-2 variants of concerns (VOCs) and interest (VOI)including WA-1, Delta and Omicron subvariants. In addition, with good human oral bioavailability, Olgotrelvir is used as a standalone oral drug without the need of ritonavir, making the treatment available for a broader population with underlying conditions requiring medications incompatible with ritonavir. At present, Olgotrelvir has been approved for clinical research in China, the United States, and Australia. Two Phase 1 clinical studies (Trial ID: NCT05364840 and NCT05523739) have been completed in Australia and China, and a Phase 3 clinical study (Trial ID: NCT05716425). The data unblinding and statistical analysis of phase 3 trial of 1200 Covid-19 patients are completed in China. In addition, the drug-drug interaction (DDI) and Mass Balance (C14) clinical studies are completed in China. NDA application is planned in China by the end of 2023, while emergency listing (EUA) application is expected in Mexico, and Phase II/III clinical trials are planned in the United States.

Inhibition of human cathepsin L by Olgotrelvir opens the possibility for other drug applications. It is anticipated that Olgotrelvir will be developed for the treatment of other diseases such as chronic obstructive pulmonary disease (COPD), and other infectious diseases with pathogens depending on cathepsin L for entry into host cells.

Investigator Initiated Trials (IIT)

We believe in supporting healthcare providers via Investigator Initiated Trials (IIT) to improve the medical and scientific knowledge of our compounds in clinical development. An IIT may be a clinical or non-clinical study for which ACEA provides funding and/or drug compound. For clinical studies, our focus is on trials that evaluate Abivertinib in adults with solid tumors or blood cancer as a stand-alone agent or in combination therapy regimens (requests outside of this area will not be considered at this time).

We support IITs that will:

• Contribute knowledge to the medical and scientific community
• Address unmet needs of patients and their healthcare providers
• Have outcomes communicated in an appropriate scientific forum, including peer-reviewed publications

Examples of appropriate requestors of IIT support include, but are not limited to:

• Healthcare providers and their institutions
• Members of the scientific community and their institutions (colleges and universities)
• Government research institutions

If you are interested in evaluating abivertinib or any of our other pipeline compounds for potential use in the treatment of cancer or autoimmune disease, please contact us at ACEA-IIT@aceatherapeutics.com.