<< Back
View printer-friendly version
Aptevo Therapeutics Showcases New Mechanism of Action for Its ADAPTIR Platform at the Inflammation Research Society Meeting

New Autoimmune Candidate APVO210 Demonstrates Targeted Cytokine Delivery for Application in Various Autoimmune and Inflammatory Diseases

SEATTLE, Oct. 16, 2017 (GLOBE NEWSWIRE) --  Aptevo Therapeutics Inc. (Nasdaq:APVO), a biotechnology company focused on developing novel immuno-oncology and hematology therapeutics, today announced that it presented information on a new ADAPTIR™ candidate, APVO210, at the Inflammation Research Association meeting in Seattle, WA, October 13, 2017.

In a presentation entitled, “APVO210 an ADAPTIR Targeted Cytokine Delivery Molecule for Autoimmune and Inflammatory Diseases,” Dr. Gabriela Hoyos, presented an overview of Aptevo’s novel ADAPTIR candidate, APVO210, designed to deliver an immunosuppressive cytokine to modulate the body’s inflammatory response in various autoimmune and inflammatory conditions like irritable bowel disease (IBD), rheumatoid arthritis (RA) and transplant related disorders such as graft versus host disease.

Cytokines function by promoting or suppressing a variety of cellular functions, including inflammatory responses.  Unregulated inflammation can result in disease and chronic inflammatory conditions like IBD.  IL-10 is a cytokine that is known to suppress inflammation.  However, IL-10 also has stimulatory functions on lymphocytes, enhancing B cell proliferation and cytotoxic T cell function, reducing its potential anti-inflammatory therapeutic properties.   

APVO210 is a novel targeted cytokine therapeutic based on Aptevo’s ADAPTIR modular protein therapeutic platform.  It targets a modified version of IL-10 to CD86+ cells, increasing its immunosuppressive properties without stimulating T and B lymphocytes, as demonstrated in preclinical studies.  APVO210 improves the anti-inflammatory properties of IL-10 in two ways. First by specifically targeting cells expressing CD86, such as monocyte, macrophage, and dendritic cells, and secondly by delivering a modified form of IL-10 that does not stimulate lymphocytes. This lack of lymphocyte stimulation may reduce the toxicities previously observed following repeat administration of IL-10 in humans, and potentially allow for increased dosing. In addition, APVO210 has demonstrated a longer half-life in non-human primates and may improve dosing regimens.

Preclinical data confirm the mechanism of action of APVO210 and show the effective targeting of APVO210 to antigen presenting cells with limited effects on lymphocytes. Pharmacokinetic studies also demonstrate that APVO210 is potent and well tolerated in preclinical models at doses up to 10 mg/kg in single dose studies in non-human primates, and 30-fold more potent than CTLA4-Ig in in vitro and in vivo animal systems.

Additionally, preclinical data show proof of concept for APVO210 in a humanized transplant model.  In a prophylactic model of graft versus host disease (GvHD), APVO210 showed strong inhibition of T cell expansion at very low doses (~70 ug/kg) and reduced the accumulation of cytokines in circulation.  In this model, APVO210 was 100-fold more potent than abatacept at maximum inhibition of T cell expansion.

“Targeted cytokine delivery represents an evolving approach for the treatment of autoimmune and inflammatory diseases and we are excited to expand the application of our ADAPTIR technology platform to include additional candidates like APVO210, featuring a novel mechanism of action distinct from redirected T cell cytotoxicity (RTCC), which is the basis of many of our ADAPTIR oncology candidates,” remarked Dr. Jane Gross, Chief Scientific Officer for Aptevo.  “Modulating the immune system using a bispecific antibody opens up new frontiers in the treatment of many debilitating and serious autoimmune disorders with high unmet medical need and the preclinical data for APVO210 suggest it may be effective in the treatment of such disorders.  We are very encouraged by the preclinical data and look forward to advancing APVO210 towards clinical development.”  

ADAPTIR Bispecific Antibody Platform: Differentiating Characteristics

  • Unique Homodimer Structure - simplifies candidate generation; facilitates rapid substitution of target binding domains to evaluate numerous candidates simultaneously
  • Bivalent for Both Binding Domains - increases the avidity and potency of ADAPTIR candidates
  • Unique IgG Fc ‘Backbone’ - extends the half-life of ADAPTIR molecules (up to ~12.5 days in rodents)
  • Antibody-like Production Processes – demonstrated capability to produce up to 2.0g/L comparable to traditional antibody manufacturing processes
  • Improved Yield and Cost of Goods - use of a single gene and ease of CHO cell line production enhances ADAPTIR bispecific manufacturing productivity
  • Flexible Platform Technology – ability to produce protein therapeutics with different structural elements fused to an antibody backbone for different mechanisms of action.

ADAPTIR Clinical and Preclinical Portfolio:

  • APVO414 – a bispecific ADAPTIR candidate, currently in Phase 1 development, targeting prostate specific membrane antigen (PSMA), an enzyme that is expressed on the surface of prostate cancer cells, and, CD3, a component of the T cell receptor complex expressed on all T cells.  APVO414 redirects T cells to specifically kill PSMA expressing tumors and is being developed for metastatic castration-resistant prostate cancer, which is advanced prostate cancer that has spread to other organs and no longer responds to hormone blocking therapies.
  • Otlertuzumab – a monospecific ADAPTIR candidate currently in Phase 2 development for the treatment of chronic lymphocytic leukemia (CLL).  Data from a Phase 2 clinical trial evaluating otlertuzumab in combination with bendamustine, compared to bendamustine alone, demonstrated a significant increase in median progression free survival for the combination, from approximately 10 to 16 months.
  • APVO436 – a bispecific ADAPTIR candidate currently in preclinical development targeting CD123, a cell surface receptor highly expressed on several hematological malignancies and CD3, a component of the T-cell receptor. APVO436 engages T cells to kill tumor cells.
  • ALG.APV-527 – a bispecific antibody candidate, partnered with Alligator Bioscience, featuring a novel mechanism of action designed to simultaneously target 4-1BB (CD137) and an undisclosed tumor antigen.  4-1BB, a costimulatory receptor on T cells, is known to enhance the immune response to cancer through activation of tumor-specific T cells and is believed to be a promising target for new immunotherapeutic approaches. ALG.APV-527 could potentially have utility in the treatment of a broad spectrum of cancers over-expressing the tumor antigen, in multiple solid tumors including breast, cervical, non-small-cell-lung, prostate, renal, gastric, colorectal and bladder cancers.
  • APVO210 – a bispecific ADAPTIR preclinical candidate with a novel mechanism of action based on targeted cytokine delivery.  APVO210 is composed of a humanized anti-CD86 antibody fused with a modified form of IL-10 that specifically induces IL-10 signaling on antigen presenting cells, but not on lymphoid populations. APVO210 functions by suppressing immune responses and inducing certain tolerogenic responses and therefore may have potential benefit for the treatment of autoimmune and inflammatory diseases.
  • ROR1 Bispecific – a proof-of-concept bispecific candidate targeting ROR1, an antigen found on several solid tumors and hematologic, or blood-related malignancies.  Initial preclinical data demonstrate redirected T cell killing of tumors expressing ROR1 in vitro and in vivo in animal models.

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®, 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, 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 possible negative effects on our business operations, assets or financial results as a result of the closing of the transaction;; a deterioration in Aptevo’s business or prospects; the parties may be unable to achieve the anticipated benefits of the transaction; 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 31, 2017, 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.

For Further Information:

Aptevo Therapeutics
Stacey Jurchison
Senior Director, Investor Relations and Corporate Communications

Primary Logo

Source: Aptevo Therapeutics