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New Preclinical Data Presented at the 2018 American Association for Cancer Research Annual Meeting Show Potent T-Cell Directed Tumor Killing with Reduced Cytokine Production Compared to a Competitor Bispecific Construct
SEATTLE, April 16, 2018 (GLOBE NEWSWIRE) -- Aptevo Therapeutics Inc. (Nasdaq:APVO), a biotechnology company focused on developing novel oncology and hematology therapeutics, today announced the presentation of new data for APVO436, a bispecific antibody candidate targeting CD123 and CD3, at the American Association for Cancer Research (AACR) 2018 Annual Meeting. The preclinical data demonstrate potent T-cell cytotoxicity of tumors expressing CD123 with limited cytokine release and suggest that APVO436 has the potential for increased clinical benefit and a favorable safety profile.
Cytokine release syndrome (CRS) is a significant concern with T-cell activating therapies and has been associated with severe complications in clinical trials. Aptevo has previously published data on its first generation candidate, APVO414, showing reduced cytokine release upon T-cell engagement compared to another bispecific format (Mol Cancer Ther. 2016 Sep; 15(9); 2155-65).
New preclinical data presented at this year’s AACR Annual Meeting compare Aptevo’s second generation bispecific, APVO436, with an Aptevo-generated version of Macrogenics’ CD123 x CD3 dual-affinity re-targeting (DART) molecule, MGD006, evaluating T-cell activation, proliferation, cytotoxicity and cytokine secretion.
The data show that APVO436 and the Aptevo-generated version of MDG006 are both effective at stimulating a tumor-directed immune response by inducing comparable T-cell activation, proliferation and cytotoxicity. However, in these preclinical studies, APVO436 induced lower levels of several T-cell cytokines, including IFNγ, IL-2, IL-6, TNFα and several additional cytokines, suggesting a potential safety advantage with APVO436.
“We are especially excited about these latest data for APVO436, which continue to show robust T-cell engagement and cytotoxic activity with reduced levels of cytokine release. Importantly, IFNγ, IL-6, and TNFα are considered to be the most relevant cytokines responsible for dosing toxicities observed in clinical studies with T-cell engaging molecules, which suggests that APVO436 could offer the potential for reduced toxicities compared to other CD123 x CD3 T-cell engagers at comparable or higher doses,” said Jane Gross, Ph.D., Senior Vice President and Chief Scientific Officer for Aptevo.
“The accumulating data for APVO436 showing enhanced stability, extended half-life in rodents of up to 12.5 days, desirable manufacturing characteristics, and reduced cytokine release in preclinical studies, support our assessment of APVO436 as a “Best-in-Class” anti-CD123 x anti CD3 immunotherapeutic. We plan to file an IND for APVO436 in the upcoming weeks and commence a Phase 1 clinical trial of APVO436 later this year in acute myeloid leukemia and myelodysplastic syndrome,” noted Dr. Gross.
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 traditional chemotherapy. The American Cancer Society estimates that approximately 20,000 new cases of AML are diagnosed each year in the United States.
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 American Cancer Society estimates that approximately 10,000 new cases of MDS are diagnosed each year in the United States.
In a poster session on Monday, April 16, 2018, Aptevo scientists presented comprehensive data from a series of preclinical studies of APVO436 showing it is a potent inducer of redirected T-cell killing of AML tumor cells both in vitro and in vivo through the dual targeting of CD123 (a cell surface receptor highly expressed in several hematological malignancies) and CD3 (a T-cell co-receptor that promotes cytotoxicity.)
The data presented show that APVO436:
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. Two ADAPTIR molecules are currently in clinical development, with several more ADAPTIR bispecific immunotherapies in preclinical development.
Aptevo Product Portfolio
ADAPTIR Clinical and Preclinical Pipeline:
About Aptevo Therapeutics Inc.
Aptevo Therapeutics Inc. is a clinical-stage biotechnology company focused on novel oncology and hematology therapeutics to meaningfully improve patients’ lives. Aptevo has a commercial product, IXINITY® coagulation factor IX (recombinant), approved and marketed in the United States for the treatment of Hemophilia B, and a versatile core technology – the ADAPTIR™ modular protein technology platform capable of generating highly-differentiated bispecific antibodies with unique mechanisms of action to treat cancer or autoimmune diseases. Aptevo has two ADAPTIR antibody candidates currently in clinical development and a broad pipeline of novel investigational-stage bispecific antibody candidates focused in immuno-oncology and autoimmune disease and inflammation. For more information, please visit www.aptevotherapeutics.com
Safe Harbor Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Any statements, other than statements of historical fact, including, without limitation, statements regarding potential milestone payments, Aptevo’s outlook, financial performance or financial condition, Aptevo’s technology and related pipeline, collaboration and partnership opportunities, commercial portfolio, milestones, and any other statements containing the words “believes,” “expects,” “anticipates,” “intends,” “plans,” “forecasts,” “estimates,” “will” and similar expressions are forward-looking statements. These forward-looking statements are based on Aptevo’s current intentions, beliefs and expectations regarding future events. Aptevo cannot guarantee that any forward-looking statement will be accurate. Investors should realize that if underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could differ materially from Aptevo’s expectations. Investors are, therefore, cautioned not to place undue reliance on any forward-looking statement. Any forward-looking statement speaks only as of the date of this press release, and, except as required by law, Aptevo does not undertake to update any forward-looking statement to reflect new information, events or circumstances.
There are a number of important factors that could cause Aptevo’s actual results to differ materially from those indicated by such forward-looking statements, including a deterioration in Aptevo’s business or prospects; adverse developments in research and development; adverse developments in the U.S. or global capital markets, credit markets or economies generally; and changes in regulatory, social and political conditions. Additional risks and factors that may affect results are set forth in Aptevo’s filings with the Securities and Exchange Commission, including its most recent Annual Report on Form 10-K, as filed on March 13, 2018 and its subsequent reports on Form 10-Q and current reports on Form 8-K. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from Aptevo’s expectations in any forward-looking statement.
Senior Director, Investor Relations and Corporate Communications
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