Aptevo Therapeutics Announces IND Submission for APVO436

New Preclinical Data Presented at AACR Support Best-in-Class Features of APVO436 Highlighting Reduced Cytokine Release and Antibody-Like Half-Life and Manufacturing

On Track to Commence Phase 1 Clinical Trial of APVO436 in Acute Myeloid Leukemia and Myelodysplastic Syndrome in Q4 2018

SEATTLE, May 01, 2018 (GLOBE NEWSWIRE) -- Aptevo Therapeutics Inc. (Nasdaq:APVO), a biotechnology company focused on developing novel oncology and hematology therapeutics, today announced that it has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) to evaluate APVO436 in a Phase 1 clinical study for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). 

Dr. Scott C. Stromatt, Chief Medical Officer for Aptevo, remarked, “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. In contrast, an immunotherapy such as APVO436, which recruits the patient’s own immune system to kill leukemic cells could offer a safer and more effective therapy.”

The planned Phase 1/1b clinical trial will be conducted in two parts, the first being an open-label, dose-escalation study to evaluate the safety and pharmacokinetic profile of APVO436 to determine a maximum-tolerated dose and recommended dose for part 2. The second part of the study will be 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.

“We are very encouraged by recent preclinical data presented by Aptevo at the American Association for Cancer Research annual meeting, which support our assessment of APVO436 as a best-in-class CD123 x CD3 immunotherapeutic,” continued Dr. Stromatt. “We compared APVO436 to 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. While both molecules showed potent T-cell activation, proliferation and cytotoxicity, APVO436 induced lower levels of several key T-cell cytokines, which are believed to be responsible for dosing toxicities observed in other companies' clinical studies, in particular, IFNg, IL-2, IL-6, TNFa. While these data would need to be confirmed in the clinic, it does suggest that APVO could have an enhanced safety profile at comparable or higher doses. The IND filing for APVO436 is an important milestone for our ADAPTIR platform as we advance APVO436, our first next generation ADAPTIR candidate towards clinical development.”

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. Two ADAPTIR molecules are currently in clinical development, with several more ADAPTIR bispecific immunotherapies in preclinical development.

Aptevo Product Portfolio

Marketed Product:

• IXINITY (coagulation factor IX [recombinant]) – is a third-generation recombinant human coagulation factor IX approved in the United States for the control and prevention of bleeding episodes and for perioperative management in adults and children 12 years of age or older with Hemophilia B.

ADAPTIR Clinical and Preclinical Pipeline:

• Otlertuzumab – a monospecific ADAPTIR candidate currently in Phase 2 clinical development for the treatment of peripheral T-cell lymphoma (PTCL). A previous Phase 2 clinical study evaluating otlertuzumab for the treatment of chronic lymphocytic leukemia (CLL) showed that 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.
• 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.
• APVO436 – a bispecific ADAPTIR candidate 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 initiate killing of tumor cells. Aptevo filed an IND in Q2 2018 and plans to begin clinical development of APVO436 in Q4 2018.
• 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 5T4, a tumor antigen widely overexpressed in a number of different types of cancer. 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, 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. Aptevo intends to file an IND for APVO210 in 2018.
• 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^® 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.

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.