Aptevo Therapeutics Doses First Patient in Phase 1/1b Clinical Trial of Lead Next-Generation Bispecific Antibody APVO436
Preclinical Data for APVO436 Show Potential Best-in-Class Attributes with Potent T-Cell Directed Tumor Killing and Reduced Cytokine Production Compared to a Competitor Construct
Phase 1/1b Clinical Trial to Evaluate Safety Profile and Determine the Recommended Dose of APVO436 in Patients with Acute Myeloid Leukemia and High-Grade Myelodysplastic Syndrome
As a novel immunotherapy, APVO436 is designed to engage the immune system to mount a targeted response against CD123-expressing hematological tumors. Cytokine release syndrome (CRS) is a significant concern with T-cell activating therapies and has been associated with severe complications in clinical trials. In preclinical studies, APVO436 induced lower levels of several key T-cell cytokines, including IFNg, IL-2, IL-6, and TNFa. Aptevo believes that the improved cytokine activation profile observed in preclinical studies of APVO436 suggest that it could offer a potential safety advantage with reduced toxicities compared to other CD123 x CD3 T-cell engagers at comparable or higher doses.
“Today’s news represents an important milestone for Aptevo and for AML and MDS patients,” said Dr.
Preclinical data show that APVO436 is a potent inducer of redirected T-cell killing of AML tumor cells both in vitro and in vivo. When compared head-to-head against an Aptevo-generated version of a competitor molecule, (Macrogenics’ CD123 x CD3 dual-affinity re-targeting (DART) molecule, MGD006), the data show that both were effective at stimulating a tumor-directed immune response and induced comparable T-cell activation, proliferation and cytotoxicity. However, APVO436 induced lower levels of several key T-cell cytokines, including IFNg, IL-2, IL-6, TNFa, which have been associated with serious adverse events in clinical studies.
The APVO436 Phase 1/1b clinical trial will be conducted in two parts. The first part will enroll up to 60 patients and is an open-label, dose-escalation study evaluating the safety and pharmacokinetic profile of APVO436 to determine a recommended dose for part 2. The second part of the study is a Phase 1b open-label expansion study to assess the clinical activity and safety profile of APVO436 at the recommended dose in a larger group of patients.
“APVO436 is our first bispecific antibody candidate developed based on Aptevo’s next-generation ADAPTIR platform to enter the clinic,” continued Dr. Stromatt. “Our next-generation ADAPTIR platform has been optimized to construct novel bispecific antibody therapeutics that maintain the desirable properties of traditional antibodies, such as longer half-life, stability and ease of manufacturing, but with the potential to exploit novel mechanisms of action to achieve enhanced biological activity and an improved therapeutic index. The recent clinical data for bispecific CD3/CD123 T-cell engagers looks very promising, and we are eager to see if the advantages shown in preclinical studies with APVO436 will be confirmed in the clinic. We anticipate reporting preliminary top-line data from the Phase 1 study later in 2019.”
About AML and MDS
Acute myeloid leukemia (AML) is a form of blood and bone marrow cancer that is characterized by rapid disease progression. While treatments for AML are available, there remains a high unmet medical need for targeted therapies addressing patients with relapsed and refractory disease, and patients who cannot tolerate chemotherapy. There are estimated to be approximately 100,000 new cases of AML diagnosed worldwide each year(1), while the
Myelodysplastic syndromes (MDS) are conditions associated with abnormalities in the blood-forming cells in the bone marrow. Approximately 1 in 3 patients with MDS will progress to have AML. The incidence of MDS in the six major world markets is estimated to be approximately 33,000 per year(3), while the
About APVO436 and the ADAPTIR Platform
APVO436 is an optimized, next generation bispecific antibody candidate designed to simultaneously target CD123 and CD3 and redirect T-cell cytotoxicity to the tumor. APVO436 was built on Aptevo’s proprietary ADAPTIR protein therapeutic platform. Focused on generating novel, targeted bispecific antibody-based immunotherapies for cancer and autoimmune diseases, the ADAPTIR platform offers key advantages over other bispecific formats, derived in part from the flexible and modular nature of the ADAPTIR structure. These advantages include: (i) achieving potent biological activity and extended half-life while retaining desirable manufacturing characteristics; (ii) unique properties for redirecting T-cell cytotoxicity (RTCC) compared to other bispecific platforms, including a favorable cytokine release profile; (iii) ability to achieve target-dependent induction of RTCC at lower concentrations than other bispecific antibody formats; and (iv) flexibility to build ADAPTIR candidates with diverse mechanisms of action, including RTCC, and targeted cytokine release and others.
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Senior Director, Investor Relations and Corporate Communications
206-859-6628 / JurchisonS@apvo.com
(2) Global Data; Data represent the therapeutics segment only. Incident Cases (N) represent the number of Diagnosed Incident cases of Acute Myeloid Leukemia. Forecast data for epidemiology parameters are based on EpiCast model which provides data for the 16MM (US,
(3) Decision Resources; Data represents male and female patients of all ages from
Source: Aptevo Therapeutics Inc.