Aduro Biotech Announces Clinical Program Update for Anti-APRIL Antibody BION-1301

• First healthy volunteer cohort cleared in Phase 1 first-in-human study of BION-1301 for the treatment of IgA nephropathy (IgAN); initial data in healthy volunteers expected in H1 2020 and IgAN patients in H2 2020
   
• Results from the dose escalation portion of the Phase 1/2 study in relapsed or refractory multiple myeloma (MM) patients whose disease progressed after at least three prior therapies indicated BION-1301 was well tolerated across a wide dose range and no dose limiting toxicities (DLTs) were observed
   
• 95% target engagement achieved and maintained; no objective responses observed in the MM patient setting
   
• Phase 1 dose escalation data in MM to be presented at the 2019 ASCO Annual Meeting

BERKELEY, Calif., May 15, 2019 (GLOBE NEWSWIRE) -- Aduro Biotech, Inc. (NASDAQ: ADRO), a clinical-stage biopharmaceutical company focused on developing therapies targeting the Stimulator of Interferon Genes (STING) and A Proliferation Inducing Ligand (APRIL) pathways for the treatment of cancer, autoimmune and inflammatory diseases, today provided an update on its clinical development programs for BION-1301, a first-in-class humanized IgG4 monoclonal antibody that fully blocks APRIL binding to both the BCMA and TACI receptors.
  
“We believe the clinical potential for BION-1301 is rooted in scientific rationale and we will pursue the development of BION-1301 in the IgAN indication, where we believe there is significant opportunity to address unmet patient need. We are pleased to initiate this study as a first step in evaluating BION-1301’s ability to reduce the autoimmune deposition of immune complexes affecting kidney function, and its potential to become a meaningful treatment option for this progressive kidney disease,” said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro.  “However, with the emergence of transformative therapeutic options for multiple myeloma, we have determined not to continue the current Phase 1/2 study as designed in this setting. Although no objective responses were observed, we believe there is potential for investigator-sponsored trials of BION-1301 in combination with other approved agents, given the excellent tolerability profile and PK-PD data.”

BION-1301 in IgA Nephropathy

The first cohort of healthy volunteers has been cleared in a Phase 1 multicenter study (see www.clinicaltrials.gov, identifier: NCT03945318) designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of BION-1301 in healthy volunteers and adults with IgAN. The study, which will enroll up to 63 healthy subjects and up to 10 subjects with IgAN, will be conducted in three parts: Part 1 is a double-blind, randomized, placebo-controlled, single ascending dose in healthy volunteers; Part 2 is a double-blind, randomized, placebo-controlled multiple ascending dose in healthy volunteers; and Part 3 is an open-label, multiple dose in subjects with IgAN.

“There are currently no approved therapeutic options for IgAN patients. We believe BION-1301’s mode of action may target the production of galactose-deficient IgA as well as the autoantibody response to IgA, two key steps in the disease etiology preceding the formation of immune complexes in the kidney and subsequent loss of renal function,” said Andrea van Elsas, Ph.D., chief scientific officer of Aduro. “In addition to assessing the safety profile and PK-PD relationship of BION-1301 in healthy volunteers and IgAN patients in this study, we are looking to establish proof-of-mechanism.”

Preclinical studies have demonstrated that BION-1301 binds to a specifically defined epitope on APRIL, resulting in complete blockade of APRIL-induced receptor activation. Dosing of BION-1301 in non-human primates led to a significant reduction of blood IgA levels and established a favorable safety profile. Preclinical studies demonstrated that hAPRIL transgenic mice produce rising levels of IgA as well as IgA deposits in the kidney. Administration of mouse anti-human APRIL was shown to reduce levels of IgA in both the serum and the kidney.

BION-1301 in Relapsed/Refractory Multiple Myeloma

Aduro completed the dose escalation portion of its Phase 1/2 study evaluating safety and tolerability in patients with relapsed or refractory MM whose disease had progressed after at least three prior systemic therapies. Results demonstrated that BION-1301 was well tolerated in patients with relapsed or refractory MM across a wide dose range and no DLTs were observed at any dose levels. While 95% target engagement was achieved at peak exposure levels and levels of free APRIL decreased dose-dependently, no objective responses were observed. 

Aduro does not intend to proceed to the Phase 2 portion of the ongoing Phase 1/2 study or initiate further company-sponsored studies in the MM patient setting. Aduro is working closely with thought leaders to assess the direction of the BION-1301 MM program, including through potential investigator-sponsored studies.

Two abstracts highlighting data from the Phase 1/2 study will be presented on Monday, June 3 at the 2019 ASCO Annual Meeting in Chicago, IL. Details of the poster presentations are as follows:

To view these and other Aduro abstracts, please visit the ASCO website at http://abstracts.asco.org/.

About IgA Nephropathy
IgA nephropathy is a progressive kidney disease characterized by an autoimmune antibody response against endogenous immunoglobulin A (IgA). The accumulation of autoantibodies binding to galactose-deficient IgA leads to deposition of immune complexes in the glomeruli of the kidneys. This results in local inflammation impeding kidney function, which may eventually lead to end-stage renal disease and the need for renal transplant. While IgA nephropathy has unclear causality and lacks approved disease-modifying options for therapy, preclinical data indicate that suppressing serum IgA1 and the anti-IgA autoimmune response by a neutralizing APRIL antibody, such as BION-1301, may reduce the progression and severity of proteinuria and other symptoms.

About BION-1301
BION-1301 is a first-in-class humanized IgG4 monoclonal antibody that fully blocks APRIL binding to both the BCMA and TACI receptors, and is being developed as a novel therapy for IgA nephropathy. BION-1301 has been shown in preclinical studies to reduce serum IgA levels in mice and monkeys.

About Aduro
Aduro Biotech, Inc. is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of therapies that are designed to harness the body’s natural immune system for the treatment of patients with challenging diseases. Aduro’s product candidates in the Stimulator of Interferon Genes (STING) and A Proliferation Inducing Ligand (APRIL) pathways are being investigated in cancer, autoimmune and inflammatory diseases. ADU-S100 (MIW815), which potentially activates the intracellular STING receptor for a potent tumor-specific immune response, is being evaluated in patients with cutaneously accessible metastatic solid tumors or lymphomas. BION-1301, a first-in-class humanized IgG4 monoclonal antibody that fully blocks APRIL binding to both the BCMA and TACI receptors, is being evaluated in IgA nephropathy. Aduro is collaborating with a number of leading global pharmaceutical companies to help expand and drive its product pipeline. For more information, please visit www.aduro.com.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding our intentions or current expectations concerning, among other things, the potential for BION-1301 to become a meaningful treatment option for IgAN and address unmet patient need, the mechanism of action for BION-1301 in treatment of IgAN, including the ability of BION-1301 to target galactose-deficient IgA and the autoantibody response to IgA and to reduce autoimmune immune complex deposition affecting kidney function, our ability to establish proof of mechanism of BION-1301 as a treatment option for IgAN in the Phase 1 study, the direction of BION-1301 for treatment of MM, including any potential investigator sponsored studies of BION-1301 alone or with other approved agents for treatment of MM, the timing and volume of clinical data, and our ability to expand and drive our product pipeline alone or with our collaborators. In some cases, you can identify these statements by forward-looking words such as “may,” “will,” “continue,” “anticipate,” “intend,” “could,” “project,” “expect” or the negative or plural of these words or similar expressions.  Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, early or preliminary clinical trial results may not be predictive of future results, our history of net operating losses and uncertainty regarding our ability to achieve profitability, our ability to develop and commercialize our product candidates, our ability to use and expand our technologies to build a pipeline of product candidates, our ability to obtain and maintain regulatory approval of our product candidates, our ability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, our reliance on third parties, and our ability to obtain and adequately protect intellectual property rights for our product candidates.  We discuss many of these risks in greater detail under the heading “Risk Factors” contained in our quarterly report on Form 10-Q for the quarter ended March 31, 2019, which is on file with the Securities and Exchange Commission. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.