SAN DIEGO and BEIJING, China and CAMBRIDGE, Mass., April 09, 2019 (GLOBE NEWSWIRE) -- BioAtla ®, LLC, a
global clinical-stage biotechnology company focused on the development of Conditionally Active Biologic (CAB) protein therapeutics,
and BeiGene, Ltd. (Nasdaq: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and
commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, today announced that the two
companies have entered into a global co-development and collaboration agreement for the development, manufacturing and
commercialization of BioAtla’s investigational CAB CTLA-4 antibody (BA3071). BA3071 is a novel, CTLA-4 inhibitor that is designed
to be conditionally activated in the tumor microenvironment in order to reduce systemic toxicity and potentially enable safer
combinations with checkpoint inhibitors such as BeiGene’s investigational anti-PD-1 antibody, tislelizumab, a humanized IgG4
anti–PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages.
Under the terms of the collaboration, BioAtla will co-develop the CAB-CTLA-4 antibody to defined early clinical objectives and
BeiGene will then lead the parties’ joint efforts to develop the product candidate and be responsible for global regulatory filings
and commercialization. Subject to the terms of the agreement, BeiGene will hold a co-exclusive license with BioAtla to develop and
manufacture the product candidate globally and an exclusive license to commercialize the product candidate globally. BeiGene will
be responsible for all costs of development, manufacturing and commercialization in Asia (ex-Japan), Australia and New Zealand, and
the parties will share development and manufacturing costs and commercial profits and losses upon specified terms in the rest of
the world. BioAtla will receive an upfront payment of $20 million and a milestone payment upon reaching the defined early clinical
objectives. BioAtla is also eligible to receive up to $249 million in subsequent development and regulatory milestones globally and
commercial milestones in the BeiGene territory, together with tiered royalties on sales in the BeiGene territory. Additional terms
of the agreement were not disclosed.
“BeiGene is a recognized leader in China-inclusive global clinical development, with broad oncology clinical programs, which
include tislelizumab,” said Scott Smith, President of BioAtla. “This collaboration complements our strategy of building our
pipeline of innovative CAB oncology candidates, advancing combination product therapies, and effectively addressing markets with
strong growth potential and high unmet medical need.”
“BioAtla has developed an exciting proprietary protein discovery and expression platform to generate CABs, which in turn have
been applied to BA3071, a novel, investigational CTLA-4 inhibitor that is designed to be conditionally activated in the tumor
microenvironment,” commented Dr. Lai Wang, Senior Vice President, Asia Pacific Clinical Development, Global Research, Clinical
Operations and Biometrics, for BeiGene. “The unique nature of BA3071 provides an exciting opportunity to combine this CTLA-4
antibody with our anti-PD-1 antibody, tislelizumab. We look forward to working with BioAtla through proof-of-concept, followed by
global development of this potentially unique cancer therapy as a single agent or in combination with other therapies.”
“We believe that our collaboration with BeiGene will accelerate the global development and potential commercialization of BA3071
and advance the prospects and potential of safer and more effective combination therapies for the treatment of several cancer
indications,” stated Jay M. Short, Ph.D., Chairman, CEO and co-founder of BioAtla. “The application of BioAtla’s CAB technology to
CTLA-4 inhibition may offer greater potency and safety, thereby improving this important cancer therapy and expanding its potential
applications.”
About BA3071
BA3071 is a novel, investigational conditionally active CTLA-4 inhibitor. The first investigational new drug (IND) filing is
currently planned for mid-2019. Subject to regulatory clearance of the IND, a Phase 1/2 multi-center, open-label study designed to
evaluate the safety, tolerability, pharmacokinetics, immunogenicity and antitumor activity of BA3071 alone and in combination with
BeiGene’s tislelizumab, an investigational anti-PD-1 inhibitor, is anticipated to start in the second half of 2019.
The cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is an inhibitory receptor expressed on T cells. The CTLA-4 pathway is a
key immune checkpoint pathway that provides a downregulating signal to T cells. The blockade of CTLA-4 is intended to induce an
antitumor immune response by promoting the activation and proliferation of tumor-specific T cells. Although inhibition of CTLA-4
has been shown to significantly improve antitumor response, it may also lead to immune attack of healthy cells. To minimize
on-target off-tumor toxicity, BioAtla has applied its proprietary CAB technology with the intent to activate binding to the CTLA-4
receptor only on T cells in the tumor microenvironment.
Inhibition of immune checkpoints using anti-programmed cell death-1 (PD-1) or anti-CTLA-4 monoclonal antibodies has
revolutionized the management of patients with advanced-stage melanoma and are among the most promising components of treatment
approaches for many other cancers. Employing BioAtla’s proprietary CAB technology, BA3071 is designed to improve the efficacy and
safety of anti-CTLA-4 therapy, as a monotherapy and in combination with other therapies, by restricting its activation and that of
tumor specific T cells to the tumor microenvironment.
About Conditionally Active Biologics (CABs)
Conditionally Active Biologics are proteins generated using BioAtla’s proprietary protein discovery, evolution and expression
technologies. These proteins can be monoclonal antibodies, enzymes and other proteins designed with functions dependent on changes
in micro physiological conditions (e.g., pH level, oxidation, temperature, pressure, presence of certain ions,
hydrophobicity and combinations thereof) both outside and inside cells.
Studies have shown that cancerous tumors create highly specific conditions at their site that are not present in normal tissue.
These cancerous microenvironments are primarily a result of the well understood unique glycolytic metabolism associated with cancer
cells, referred to as the Warburg Effect in aerobic cancer cells. CAB proteins are designed to deliver their therapeutic payload
and/or recruit the immune response in specific and selected locations and conditions within the body and to be active only in the
presence of a particular cellular microenvironment. In addition, the activation is designed to be reversible to repeatedly switch
‘on and off’ should the CAB move from a diseased to a normal cellular microenvironment and vice versa. CABs can be developed in a
variety of formats, including antibodies, antibody drug conjugates (ADCs), bispecifics, chimeric antigen receptor T-cells (CAR-Ts)
and combination therapies.
About Tislelizumab
Tislelizumab (BGB-A317) is an investigational humanized IgG4 anti–PD-1 monoclonal antibody specifically designed to minimize
binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor
activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. Tislelizumab
is the first drug candidate produced from BeiGene’s immuno-oncology biologic program, and is being developed as a monotherapy and
in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.
Clinical trials of tislelizumab include a global Phase 3 clinical trial in patients with second-line non-small cell lung cancer
(NSCLC); a global Phase 3 clinical trial in first-line patients with hepatocellular carcinoma (HCC); a global Phase 3 clinical
trial in second-line patients with esophageal squamous carcinoma (ESCC); a global Phase 3 clinical trial in first-line patients
with gastric cancer (GC); a global Phase 3 clinical trial in first-line patients with ESCC; a global Phase 3 trial in patients with
Stage III NSCLC; a global Phase 2 clinical trial in second- or third-line patients with HCC; a global Phase 1 clinical trial in
patients with relapsed/refractory (R/R) NK/T-cell lymphomas; and a global Phase 1 clinical trial in patients with solid tumors. In
China, BeiGene has completed a pivotal Phase 2 clinical trial in patients with R/R classical Hodgkin’s lymphoma (cHL), and is
conducting a Phase 3 clinical trial in first-line patients with non-squamous NSCLC; a Phase 3 clinical trial in first-line patients
with squamous NSCLC; a Phase 2 clinical trial in second-line urothelial cancers (UC); and a Phase 2 clinical trial in patients with
MSI-H or dMMR solid tumors.
The new drug application (NDA) in China for R/R cHL has been accepted by the China National Medical Products Administration
(NMPA) and granted priority review.
BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumor cancers
outside of Asia (except Japan).
About BioAtla, LLC
BioAtla is a global clinical-stage biotechnology company with operations in San Diego, California, and Beijing, China. BioAtla
develops novel monoclonal antibody and other protein therapeutic product candidates designed to have more selective targeting,
greater efficacy, and more cost-efficient and predictable manufacturing than traditional antibodies. BioAtla has two programs
currently in Phase 1/2 clinical testing in the United States, BA3011, a novel conditionally active AXL-targeted antibody-drug
conjugate (CAB-AXL-ADC), and BA3021, a novel conditionally active ROR2-targeted antibody-drug conjugate (CAB-ROR2-ADC).
About BeiGene
BeiGene is a global, commercial-stage, research-based biotechnology company focused on molecularly-targeted and
immuno-oncology cancer therapeutics. With a team of over 2,200 employees in China, the United
States, Australia and Europe, BeiGene is advancing a pipeline consisting of novel oral small molecules and
monoclonal antibodies for cancer. BeiGene is also working to create combination solutions aimed to have both a meaningful
and lasting impact on cancer patients. BeiGene markets ABRAXANE® (nanoparticle albumin–bound paclitaxel),
REVLIMID® (lenalidomide), and VIDAZA (azacitidine) ® in China under a license
from Celgene Corporation.1
BeiGene Cautionary Note Regarding BeiGene’s Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of
1995 and other federal securities laws, including statements regarding future research, development and potential commercialization
activities under the agreement with BioAtla, potential payments payable to BioAtla, the speed and outcome of drug development
plans, the advancement of and anticipated clinical development, regulatory milestones and commercialization of BA3071 and
tislelizumab, potential advantages and differentiation of BA3071 and tislelizumab, BioAtla’s and BeiGene’s development and
commercial plans, and other information that is not historical information. Actual results may differ materially from those
indicated in the forward-looking statements as a result of various important factors, including BeiGene’s ability to demonstrate
the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further
development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical
trials and marketing approval; BeiGene’s ability to achieve commercial success for its marketed products and drug candidates, if
approved; BeiGene’s ability to obtain and maintain protection of intellectual property for its technology and drugs; BeiGene’s
reliance on third parties to conduct drug development, manufacturing and other services; BeiGene’s limited operating history and
BeiGene’s ability to obtain additional funding for operations and to complete the development and commercialization of its drug
candidates, as well as those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent annual
report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene’s subsequent
filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this
press release, and BeiGene undertakes no duty to update such information unless required by law.
1 ABRAXANE®, REVLIMID®, and VIDAZA® are registered trademarks of Celgene
Corporation.
