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

SEATTLE, Dec. 13, 2018 (GLOBE NEWSWIRE) -- Aptevo Therapeutics Inc. APVO, a biotechnology company focused on developing novel oncology and hematology therapeutics, announced today that the first patient has been dosed in a Phase 1/1b clinical trial of APVO436, a novel anti-CD123 by anti-CD3 bispecific antibody based on Aptevo's ADAPTIR™ technology, which is being developed for the treatment of patients with Acute Myeloid Leukemia (AML) and High-Grade Myelodysplastic Syndrome (MDS).

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. Scott Stromatt, Chief Medical Officer for Aptevo.  "There is a strong unmet medical need for novel targeted biological therapies to treat patients with relapsed or refractory AML or MDS.  Chemotherapy, which is the standard of care for these patients, is generally poorly tolerated in the elderly, and patients are still confronted with high relapse rates after treatment.  Recent clinical data has demonstrated that CD123 is a validated target for AML therapy. We are particularly excited to begin clinical evaluation of APVO436 as our preclinical data suggest that it possesses best-in-class attributes and could offer benefits compared to current investigational therapies."

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 American Cancer Society estimates that approximately 20,000 new cases of AML are diagnosed each year in the United States alone.⁽²⁾ 

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 American Cancer Society estimates that approximately 10,000 new cases of MDS are diagnosed each year in the United States alone.⁽²⁾

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.

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 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.

Source:
Aptevo Therapeutics
Stacey Jurchison
Senior Director, Investor Relations and Corporate Communications
206-859-6628 / JurchisonS@apvo.com
  

(1)  https://www.cancer.org/cancer/acute-myeloid-leukemia/about/key-statistics.html

(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, France, Germany, Italy, Spain, UK, Japan, Australia, Brazil, Canada, China, India, Mexico, Russia, South Africa, and South Korea).

(3)  Decision Resources; Data represents male and female patients of all ages from the United States, France, Germany, Italy, Spain, and the United Kingdom.