ALX Oncology Holdings Inc. is focused on developing innovative cancer therapies, particularly through their lead product candidate, evorpacept (ALX148), which is a next-generation checkpoint inhibitor targeting the CD47 pathway. This pathway is exploited by cancer cells to evade the immune system by sending a "don't eat me" signal to macrophages. Evorpacept is designed to have a high affinity for CD47 while minimizing hematologic toxicities that are often associated with other CD47 blocking therapies. The unique design of evorpacept, which includes two engineered high-affinity CD47 binding domains linked to an inactive Fc region of human immunoglobulin, allows for a favorable safety profile and a wide therapeutic window. This enables the potential for higher dosing and effective combination strategies with other anti-cancer agents.

The company is pursuing a dual development strategy that leverages evorpacept's ability to enhance immune responses through various combination therapies. For instance, evorpacept can be combined with anti-cancer antibodies to promote antibody-dependent phagocytosis, as seen in clinical trials for gastric and urothelial cancers. Additionally, it can be paired with PD-1/PD-L1 checkpoint inhibitors to activate T-cells, thereby improving anti-tumor activity. ALX Oncology's clinical studies, including trials like ASPEN-03 and ASPEN-04, aim to validate these mechanisms and demonstrate the efficacy of evorpacept in enhancing the effectiveness of existing cancer treatments across multiple oncology indications.

United States

ALX Oncology Holdings Inc., a clinical-stage immuno-oncology company, focuses on developing therapies for patients fighting cancer. Its lead product candidate is ALX148, a CD47 blocking therapeutic used for the treatment of myelodysplastic syndromes and acute myeloid leukemia, as well as a range of solid tumor indications, including head and neck squamous cell and human epidermal growth factor receptor 2 positive gastric/gastroesophageal junction carcinoma. The company was founded in 2015 and is based in Burlingame, California.

Cancer

ALX Oncology Holdings Inc

Head and neck cancer

The CD47 binding domain of ALX148 is an affinity enhanced extracellular &nbsp;domain of signal regulatory protein alpha, or SIRPα, a protein that is &nbsp;the natural receptor to CD47 found on myeloid cells. We have engineered &nbsp;the Fc domain of ALX148 so that it does not provide a pro-phagocytic &nbsp;signal while still maintaining an antibody-like pharmacokinetic &nbsp;half-life for the molecule. We believe our inactive Fc approach improves &nbsp;tolerability when compared to other CD47 blocking approaches that have &nbsp;an Fc domain that engages activating receptors on macrophages, causing &nbsp;phagocytosis and death of healthy cells in addition to cancer cells. &nbsp;Furthermore, ALX148 is approximately one-half the molecular weight of a &nbsp;typical antibody. ALX148’s lower molecular weight enables it to deliver &nbsp;the molar equivalent of an antibody at one half the dose. For example, a &nbsp;30 mg/kg dose of ALX148, the highest level that we have dosed to date, &nbsp;is approximately equivalent to a 60 mg/kg dose of an antibody. ALX148’s &nbsp;lower molecular weight may also facilitate increased solid tumor &nbsp;penetration and provide greater potency within the tumor &nbsp;microenvironment.
<a href="https://alxoncology.com/science/#alx148">Source</a>

Evorpacept (ALX148) + Keytruda 

Gastric cancer

Evorpacept (ALX148) + Herceptin® (trastuzumab)+Cyramza® (ramucirumab) and paclitaxel

Platinum-resistant ovarian cancer

Evorpacept (ALX148) + Keytruda  

Metastatic colorectal cancer

Evorpacept + cetuximab + pembrolizumab

Non-Hodgkin lymphoma

Evorpacept (ALX148) + rituximab and lenalidomide

Breast cancer

Evorpacept (ALX148) + Zanidatamab

Urothelial cancer

Evorpacept + enfortumab vedotin-ejfv/PADCEV® 

Evorpacept (ALX148) + ENHERTU® 

Multiple myeloma

The CD47 binding domain of ALX148 is an affinity enhanced extracellular &nbsp;domain of signal regulatory protein alpha, or SIRPα, a protein that is &nbsp;the natural receptor to CD47 found on myeloid cells. We have engineered &nbsp;the Fc domain of ALX148 so that it does not provide a pro-phagocytic &nbsp;signal while still maintaining an antibody-like pharmacokinetic &nbsp;half-life for the molecule. We believe our inactive Fc approach improves &nbsp;tolerability when compared to other CD47 blocking approaches that have &nbsp;an Fc domain that engages activating receptors on macrophages, causing &nbsp;phagocytosis and death of healthy cells in addition to cancer cells. &nbsp;Furthermore, ALX148 is approximately one-half the molecular weight of a &nbsp;typical antibody. ALX148’s lower molecular weight enables it to deliver &nbsp;the molar equivalent of an antibody at one half the dose. For example, a &nbsp;30 mg/kg dose of ALX148, the highest level that we have dosed to date, &nbsp;is approximately equivalent to a 60 mg/kg dose of an antibody. ALX148’s &nbsp;lower molecular weight may also facilitate increased solid tumor &nbsp;penetration and provide greater potency within the tumor &nbsp;microenvironment.
 
 
SARCLISA (isatuximab-irfc) is a monoclonal antibody that binds to a specific epitope on the CD38 receptor on MM cells, inducing distinct antitumor activity. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a target for antibody-based therapeutics such as SARCLISA. SARCLISA is approved in more than 50 countries, including the US and the EU, in combination with pomalidomide and dexamethasone for the treatment of patients with RRMM who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor and who progressed on last therapy. SARCLISA is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the US for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the EU for patients with MM who have received at least one prior therapy. SARCLISA continues to be evaluated in multiple ongoing phase 3 clinical studies in combination with current standard treatments across the MM treatment continuum. It is also under investigation for the treatment of other hematologic malignancies, and its safety and efficacy have not been evaluated by any regulatory authority outside of its approved indication.
<a href="https://alxoncology.com/science/#alx148">Source</a>

ALX Oncology Holdings Inc

Company Details