Aptevo Therapeutics Begins Phase 1 Clinical Trial of APVO210 a Novel Bispecific Antibody for the Treatment of Autoimmune and Inflammatory Diseases

Seattle, Washington, UNITED STATES

Unique Mechanism of Action Suppresses Inflammation and Immune Activation Without Promoting Pro-Inflammatory Lymphocyte Stimulation

Preliminary Phase 1 Data Read-outs Anticipated Q3 and Q4 2019

SEATTLE, March 20, 2019 (GLOBE NEWSWIRE) -- Aptevo Therapeutics Inc. (Nasdaq: APVO), a biotechnology company focused on developing novel oncology, autoimmune and hematology therapeutics, announced today that it has commenced dosing in a Phase 1 clinical trial of APVO210, a novel bispecific antibody candidate built on Aptevo’s ADAPTIR™ therapeutic protein platform which is being developed to treat autoimmune and inflammatory diseases.

There is a growing body of data to support APVO210 as a novel, first-in-class targeted cytokine immunotherapy.  Preclinical data published in the journal Frontiers in Immunology highlighted the activity of APVO210 as a potent and selective agent to generate a population of regulatory T cells that may play a key role in the suppression of inflammatory processes associated with pathogenic autoimmune and inflammatory conditions, such as psoriasis, inflammatory bowel disease, rheumatoid arthritis, graft-versus-host disease, and lupus, as well as other diseases where there is antigen-driven activation of T lymphocyte-mediated disease.

“Although a number of IL-10 therapeutics have been developed and tested in the clinic by other companies, the results of these studies have been disappointing, potentially due to the undesired pro-inflammatory effects of IL-10,” said Jane Gross, Ph.D., Chief Scientific Officer for Aptevo. “However, our approach with APVO210 is very different from these initial investigational compounds, as APVO210’s unique mechanism of action selectively promotes the immunosuppressive activity of IL-10 without triggering lymphocyte stimulation and also stimulates the production of the unique T-regulatory cell subset (Tr-1) which may have longer-term clinical benefit.”  

“We achieve this by using our ADAPTIR bispecific antibody scaffold to deliver a modified form of IL-10 to antigen presenting cells by targeting CD86 without stimulating IL-10 responses on resting and activated lymphocytes,” continued Dr. Gross.  “As a result, APVO210 has the potential to harness the desired anti-inflammatory effects of IL-10 without promoting concomitant undesired pro-inflammatory responses.  We are very excited to begin our clinical development program for APVO210 to determine if the preclinical properties observed to date can be replicated in a clinical setting.”

About the APVO210 Phase 1 Clinical Trial

The Phase 1 clinical trial, which is being conducted in Australia, is a randomized, double-blind, placebo-controlled, single and multiple ascending dose study of APVO210, designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of APVO210 in healthy subjects.

The study will be conducted in 2 stages; the first stage will assess single ascending doses (SAD) of APVO210, followed by an evaluation of multiple ascending doses (MAD) of APVO210 administered by intravenous (IV) infusion either weekly or biweekly over 4 weeks.  The study is expected to enroll a maximum of 64 subjects in the initial SAD dose cohort and up to 40 subjects in the MAD dose cohort.

Following a determination of a recommended clinical dose, Aptevo anticipates conducting an expansion phase of the clinical trial, which will enroll up to 40 patients with psoriasis or ulcerative colitis.  In this segment of the trial, the recommended clinical dose will be given for 12 weeks by IV infusion with the objective of gathering longer-term safety data for APVO210 and preliminary data on the clinical activity of APVO210 in this patient population.

Aptevo anticipates reporting data from the initial SAD dose cohort in the third quarter of 2019 and reporting preliminary Phase 1 safety data in the fourth quarter of 2019.

“We expect enrollment to proceed relatively quickly since APVO210 will be initially evaluated in healthy volunteers to assess safety,” commented Dr. Scott Stromatt, Chief Medical Officer for Aptevo.  “If demonstrated to be safe and effective in a clinical setting, we believe that APVO210 could represent a potentially groundbreaking new approach in the treatment of various IL-10-mediated autoimmune diseases.  As Dr. Gross noted, previous autoimmune therapeutic approaches using IL-10 have failed due to toxicity and off-target lymphocyte activation, so we are cautiously optimistic about the potential for APVO210 and look forward to important data read-outs from the clinical study later this year.”

About APVO210

Cytokines such as IL-10 function by promoting or suppressing a variety of cellular functions, including inflammatory responses.  Unregulated inflammation is believed to be responsible for a variety of chronic and acute inflammatory and autoimmune disorders.  The cytokine IL-10 is known to play a key role in suppressing inflammation, but is known to exert stimulatory effects on lymphocytes, promoting B-cell proliferation, immunoglobulin production and cytotoxic T-cell function, thus potentially reducing its overall therapeutic utility for immunosuppression.

Conversely, APVO210 is designed to deliver a modified form of IL-10 to suppress inflammation and immune activation without lymphocyte stimulation.  Importantly, APVO210 also retains the ability to mediate the differentiation of tolerogenic dendritic cells and antigen specific T regulatory cells (Tr1) 

APVO210 is believed to improve the anti-inflammatory properties of IL-10 in two ways.  First by specifically targeting cells expressing CD86, such as monocytes, macrophages, and dendritic cells, while eliminating the undesired stimulation of lymphocytes including resting and activated T and B lymphocytes expressing the IL-10 receptor.  Aptevo believes that the absence of lymphocyte stimulation associated with APVO210 may reduce the toxicities previously observed in clinical studies testing repeat administration of IL-10 in humans. If confirmed, this could potentially allow for improved dosing and enhanced efficacy.  Additionally, pre-clinical studies of APVO210 show that it has a longer half-life in non-human primates (approximately 40 hours) compared to IL-10, which is approximately 4 hours. An increased half-life should support an opportunity for improved dosing regimens.

About Autoimmune Diseases

More than 80 different types of autoimmune diseases have been identified.  Some, such as Type 1 diabetes, multiple sclerosis and rheumatoid arthritis are well known.  Others, however, are rare and difficult to diagnose.  Collectively, autoimmune diseases are among the most prevalent diseases worldwide, and in the United States, are estimated to affect more than 23.5 million people(1) while globally, autoimmune diseases are estimated to affect between 350-550 million people.(2)

About Aptevo Therapeutics Inc.

Aptevo Therapeutics Inc. is a clinical-stage biotechnology company focused on developing novel oncology, autoimmune 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 and autoimmune diseases.  Aptevo has 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 18, 2019 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.

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

(1) National Institutes of Health, National Institute of Environmental Health Sciences; https://www.niehs.nih.gov/health/topics/conditions/autoimmune/index.cfm
(2) https://www.statista.com/statistics/418328/diagnosed-autoimmune-conditions-prevalence-in-selected-countries/