New target CD40 "C-bit" out of the APX005M was awarded the FDA orphan drug title.

Recently, Apixigen, a clinical biopharmaceutical company dedicated to the development of a new generation of antibody drugs for the treatment of diseases such as tumors, announced that its single-clone antibody APX005M, which targets CD40, has been awarded FDA-granted orphan drug qualification for the treatment of esophageal and gastroesophageal connected cancers (GEJ) and pancreatic cancers.
today, let's look at the APX005M in the CD40 field.
CD40 is a key immune costitation path pathens, present on the surface of antigen-promoting cells (APC) in the immune system and plays a key role in the activation of congenital and adaptive immune system mechanisms.
the APX005M activates the endo-immune system by activating CD40 to simulate endo-immune activation, reversing immunosuppressive effects in cancer patients.
with IO, an immunosuppressant, is expected to activate APC in the tumor microencase, triggering a more effective and lasting immune response to the tumor.
APX005M was excellent in previous studies.
Esophageal cancer, GEJ and pancreatic cancer APX005M previously demonstrated encouraging anti-tumor activity in Phase 1b clinical trials (NCT02482168) and has toned safety in patients with esophageal, GEJ and pancreatic cancer.
the study included 43 patients to assess the safety and effectiveity of APX005M, with dose-limiting toxicity and adverse event (AE) rates as the primary endpoints.
end points include concentration of APX005M in the blood, presence of anti-APX005M antibody titration, and objective response rate (ORR).
In order to meet the conditions of the Phase 1b study, patients are required to be histologically diagnosed as solid tumors, and ECOG is shown to have sufficient bone marrow, liver and kidney function in a disease measurable by RECIST 1.1.
The study did not allow patients with a history of malignant or active malignancies in the blood system, patients who underwent major surgery or other research treatment within 4 weeks, uncontrolled diabetes or hypertension, history of arterial thromboembolism events, history of congestive heart failure, history of symptomatic isoemia, abnormal conduction beyond the control of routine interventions, myocardial infarction and/or known active serious infections.
30 of the selected patients received the drug and 24 were assessed for the main endpoint.
of patients (54%) experienced AE during the 32.2-week mid-level follow-up, leading to treatment interruptions.
17 per cent of patients died as a result of the progression of the disease.
in terms of the secondary endpoint of ORR, tumor shrinking was observed in 58 percent of patients, stabilization was observed in 33 percent and progress was observed in only 4 percent of patients.
The King of Cancer - Pancreatic Cancer At the 2019 annual meeting of the American Association for The Study of Cancer (AACR), APX005M-gictabin-nab-yew alcohol (NP) was accompanied or not accompanied by PD-1 antibody drugs, which attracted much attention in the industry for its previously untreated metastatic pancreatic catheterization (PDAC) patients.
the project, led by the Parker Institute for Cancer Immunotherapy (PICI) at the University of Pennsylvania, divided pancreatic cancer patients into four cohorts and included a total of 30 patients: Gissitham/nab-firol/APX005M, 0.1mg/kg (B1 queue), Gissitham/nab-yew alcohol/APX005 M, 0.3mg/kg (B2 queue), Gissytabin/nab-yew alcohol/PD-1 antibody/APX005M, 0.1mg/kg (C1 queue), gisithambin/nab-yew alcohol/PD-1 antibody/APX005M, 0.3mg/kg (C2 queue).
test results showed that the two APX005M combined drug treatment options were well-to-do, with 13 partial remissions (PR), 9 stable conditions (SDs), 1 disease progression (PD) and 1 unestarsed in 24 dose-limiting toxicity (DLT) patients, and 54.2% objective remission rate (ORR) and 92% disease control rate (DCR).
Common level 3 to 4 treatment-related adverse reactions include decreased lymphocyte count, neutral granulocyte reduction, anemia, fatigue, elevated ALT, and reduced white blood cells, and 1 patient died of stage 4 sepsis (finally determined not to be related to APX005M and PD-1 drugs).
, pancreatic cancer is actually very slow to be treated compared to most cancers.
the results confirm that CD40 astration APX005M plays a key role in activating immunity, allowing the immune system to fight cancer more effectively.
based on the positive results of the Phase I.b study, the research team will continue to advance Phase II clinical trials, which deserve further industry expectations.
currently a number of large pharmaceutical companies layout CD40 target drug development, including Viella Bio's VIB4920, Alligator Biosciences ADC-1013, Roche's RG7876 (selicrelumab) and so on, these drugs are in the clinical stage I.
to see if the APX005M officially kicks off the CD40 immunization era! Reference source: 1. Apexigen's APX005M Granted Orphan Drug Designations for the treatment of of esophageal and gastroesophageal junction cancer and for the treatment of the pancreatic cancer. News release. Apexigen. October 15, 2020. Accessed October 15, 2020.2. O'Hara MH, O'Reilly EM, Rosemarie M, et al. Abstract CT004: A Phase Ib study of CD40 agonistic monoclonal antibody APX005M together with gemcitabine (gem) and nab-paclitaxel (NP) with or without nivolumab (Nivo) intreated metastatic ductal pancreatic adenocarcinoma (PDAC) patients. Cancer Res. 2019 79 (suppl 13): CT004. doi: 10.1158/1538-7445.AM2019-CT004. 3. Complex interplay between epitope specificity and isotype dictates the biological activity of anti-human CD40 antibodies (2018). 4. Isotype Select Converts Anti-CD40 Antagonism to Agonism to Elicit Potent Antitumor Activity (2020).