Completes Dosing in Single Ascending Dose (SAD) Phase 1 Study of APVO210
Receives Approval to Begin APVO210 Multiple Ascending Dose (MAD) Study
Preliminary Data Suggest that Single Doses of APVO210 Appear to be Safe and Well Tolerated at Doses Equivalent to IL-10 Doses that Generated a Clinical Effect
in Competitor IL-10 Clinical Studies
No Anti-drug Antibodies Observed in APVO210 SAD Phase 1 Study
Based on Patient Samples Obtained to Date
APVO436 Phase 1 Clinical Study Progressing on Track;
Approval Received to Begin Dosing in Cohort 4
SEATTLE, July 25, 2019 (GLOBE NEWSWIRE) -- Aptevo Therapeutics Inc. (APVO), a biotechnology company focused on developing novel oncology, autoimmune and hematology therapeutics, announced today that it has completed dosing in a single ascending dose (SAD) Phase 1 study of APVO210, a novel investigational bispecific antibody candidate being developed for the treatment of autoimmune diseases.
Preliminary data from the SAD study show that single ascending doses of APVO210 did not cause any adverse events of concern or dose-limiting toxicities, nor were any anti-drug antibodies observed in the study based on patient samples obtained to date. As a result, Aptevo has received approval to begin the next phase of the study, evaluating multiple ascending doses of APVO210 in healthy volunteers.
“We’re extremely pleased with the rapid progress and very encouraging preliminary clinical data emerging from our APVO210 program,” said Marvin L. White, President and Chief Executive Officer. “Unlike previous competitor investigational IL-10 therapeutics, APVO210 has a unique mechanism of action that is engineered to harness the desired anti-inflammatory effects of IL-10 without promoting the undesired pro-inflammatory responses observed with other IL-10 therapeutics. We therefore believe that APVO210 has the potential to be a blockbuster new approach in the treatment of various autoimmune diseases, if APVO210 continues to be safe and well-tolerated and the clinical data confirm our preclinical observations.”
Dr. Scott Stromatt, Senior Vice President and Chief Medical Officer for Aptevo, commented, “Given that other competitor autoimmune therapeutic approaches using IL-10 have failed in the clinic due to safety and toxicity concerns, we are especially pleased by the preliminary data from our Phase 1 study, which demonstrates that single ascending doses of APVO210 of up to 320 mcg/kg produced no adverse events of concern, nor any dose-limiting toxicities. Further, no evidence of anti-drug antibodies has been observed based on patient samples obtained to date.”
“Most importantly, we demonstrated that we were able to administer APVO210 at doses that were well above comparable doses of other competitor IL-10 therapeutics that generated a clinical effect in humans in previous IL-10 clinical trials,” continued Dr. Stromatt. “With these encouraging data we are moving APVO210 rapidly into a multiple ascending dose clinical study and anticipate that dosing in the MAD study will begin in August. We look forward to reporting results from the MAD study in the first quarter of 2020, and to reporting more comprehensive data from the SAD study later this year.”
About the APVO210 Phase 1 Clinical Study
The Phase 1 clinical trial is a randomized, double-blind, placebo-controlled, single dose study to evaluate the safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics of a single dose of APVO210. A total of 64 healthy volunteers (8 Cohorts of 8 participants each) were randomized (2:6) and received placebo or escalating single doses of APVO210 as follows: 2 mcg/kg, 5 mcg/kg, 10 mcg/kg, 20 mcg/kg, 40 mcg/kg, 80 mcg/kg, 160 mcg/kg, and 320 mcg/kg by a single intravenous (IV) injection.
The objective of the study was to evaluate the safety, tolerability and pharmacokinetic parameters of a single IV dose of APVO210 in healthy subjects (follow up to Day 29). Secondary endpoints included an assessment of immunogenicity and receptor occupancy in healthy subjects.
The second part of the Phase 1 clinical trial will evaluate multiple ascending doses of APVO210. A total of 40 healthy volunteers will be grouped in 4 Cohorts (10 participants each) and will be randomized (8:10) to receive 3 or 5 doses over 29 days of APVO210 or placebo administered by IV injection. The doses being evaluated are 40 mcg/kg, 80 mcg/kg, 160 mcg/kg and 320 mcg/kg.
APVO436 Clinical Trial Update
“We also continue to be pleased with progress in our APVO436 clinical development program,” said Dr. Stromatt. “APVO436 is a novel anti-CD123 by anti-CD3 bispecific antibody that we are currently evaluating in a Phase 1/1b clinical trial in patients with Acute Myeloid Leukemia (AML) and High-Grade Myelodysplastic Syndrome (MDS). The trial is progressing well with seven clinical sites actively recruiting patients in the U.S. No dose limiting toxicities have occurred in our first 3 dosing cohorts, and importantly, no evidence of anti-drug antibodies has been observed to date in the study. We have approval to begin dosing in cohort 4 and plan to report preliminary top-line safety data later this year.”
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 is being 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.
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.
Senior Director, Investor Relations and Corporate Communications