News

BIOATLA AND BEIGENE REVISE GLOBAL DEVELOPMENT AND COMMERCIALIZATION AGREEMENT

San Diego, CA; Beijing, China and Cambridge, MA – October 6, 2020 – BioAtla, Inc., 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 biotechnology company, today announced that the two companies have revised their previous global co-development and commercialization agreement for BioAtla’s investigational CAB CTLA-4 antibody, BA3071. The previous agreement from April 2019 now becomes a global licensing agreement for BA3071, which was 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 anti-PD-1 antibody, tislelizumab.

 

Under the amended terms of the agreement, BeiGene will hold an exclusive global license to BA3071 and will be solely responsible for its global clinical development and commercialization and have the right to receive all profits on any future sales net of royalty payments to BioAtla. In addition to the upfront payment BioAtla received upon execution of the original agreement, BioAtla is eligible to receive near-term development and regulatory milestone payments together with increased tiered royalties on worldwide sales. Additional terms of the amended agreement were not disclosed.

 

“BeiGene is a recognized leader in global clinical development, with broad oncology clinical programs, including tislelizumab, its anti-PD-1 antibody which is approved in China,” said Scott Smith, President of BioAtla. “This amended agreement reflects both BeiGene’s commitment to BA3071 and BioAtla’s strategy of rapidly and broadly building our pipeline of innovative CAB oncology candidates. This amended agreement enhances BioAtla’s strategic execution capabilities to support the development of our product pipeline, advance compelling combination therapies, and address markets with strong growth potential and high unmet medical need.  BA3071 is expected to become BioAtla’s third CAB candidate in clinical trials along with CAB-AXL-ADC and CAB-ROR2-ADC.”

 

“BioAtla has developed a differentiated 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 Lai Wang, Ph.D., Senior Vice President, Head of Global Research, Clinical Operations & Biometrics and  APAC Clinical Development at BeiGene. “The unique nature of BA3071 provides us with an exciting scientific rationale to investigate the combination of this investigational CTLA-4 antibody with our anti-PD-1 antibody, tislelizumab. We look forward to advancing the global development and commercialization of this potentially unique cancer therapy as a single agent or in combination with other therapies.”

 

“We believe that our amended agreement with BeiGene will align and potentially accelerate the global development and potential commercialization of BA3071. BeiGene’s management of the global clinical trials of BA3071 in combination with BeiGene’s tislelizumab may advance the prospects of new combination therapies for the treatment of several cancer indications,” stated Jay M. Short, Ph.D., Chairman, CEO and co-founder of BioAtla. “The expanded royalty rates also recognize the exceptional opportunity that CAB technology can provide for novel combination therapies.”

 

About BA3071

BA3071 is a novel, investigational conditionally active CTLA-4 inhibitor. A Phase 1/2 multi-center, open-label study is planned to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and antitumor activity of BA3071 alone and in combination with BeiGene’s tislelizumab, an anti-PD-1 antibody. The Investigational New Drug application for BA3071 has been cleared by the U.S. Food and Drug Administration. 

 

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 is a 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 from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.

 

Tislelizumab is approved by the China National Medical Products Administration (NMPA) as a treatment for patients with classical Hodgkin’s lymphoma who received at least two prior therapies and for patients with locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

 

In addition, three supplemental new drug applications (sNDAs) for tislelizumab have been accepted by the Center for Drug Evaluation (CDE) of the NMPA and are under review, for first-line treatment of patients with advanced squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy, for first-line treatment of patients with advanced non-squamous NSCLC in combination with chemotherapy, and for previously treated unresectable hepatocellular carcinoma.

 

Currently, 16 potentially registration-enabling clinical trials are being conducted in China and globally, including 12 Phase 3 trials and four pivotal Phase 2 trials.

 

Tislelizumab is not approved for use outside of China.

 

About BioAtla, Inc.

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 biotechnology company focused on discovering, developing, manufacturing, and commercializing innovative medicines to improve treatment outcomes and access for patients worldwide. Our 4,200+ employees in China, the United States, Australia, Europe, and elsewhere are committed to expediting the development of a diverse pipeline of novel therapeutics. We currently market two internally discovered oncology products: BTK inhibitor BRUKINSA® (zanubrutinib) in the United States and China, and anti-PD-1 antibody tislelizumab in China. We also market or plan to market in China additional oncology products licensed from Amgen Inc., Celgene Logistics Sàrl, a Bristol Myers Squibb (BMS) company, and EUSA Pharma. To learn more about BeiGene, please visit www.beigene.com and follow us on Twitter at @BeiGeneUSA.

 

BeiGene 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, plans for a Phase 1/2 clinical trial of BA3071 alone and in combination with tislelizumab, BeiGene’s  other 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; the impact of the COVID-19 pandemic on BeiGene’s clinical development, commercial and other operations, as well as those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent quarterly report on Form 10-Q, 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.

 


BeiGene Contacts:

Investors

Craig West

(857) 302-5189

ir@beigene.com

 

Media

Liza Heapes or Vivian Ni

(857) 302-5663 or (857) 302-7596

media@beigene.com

 

BioAtla Contact:

Richard Waldron

Chief Financial Officer

BioAtla, Inc.

rwaldron@bioatla.com

858-356-8945

BIOATLA RAISES $72.5 MILLION IN SERIES D FINANCING

Proceeds will advance CAB-AXL and CAB-ROR2 clinical programs into Phase 2 trials, CAB-CTLA-4 Phase 1 trial, and additional CAB development programs

 
SAN DIEGO, CA
– July 15, 2020 - BioAtla, Inc., a global clinical-stage biotechnology company focused on the development of Conditionally Active Biologic (CAB) antibody therapeutics, today announced closing of a Series D financing round raising $72.5 million. The financing was led by Soleus Capital and joined by several new investors including HBM Healthcare Investments as co-lead, Cormorant Asset Management, Farallon Capital, Pappas Capital, funds managed by Janus Henderson, Boxer Capital, and one other institutional investor. Current investor Pfizer Ventures, the venture capital arm of Pfizer Inc. (NYSE: PFE), also participated in the financing.

“The funding provided by this group of highly respected investors strongly supports the execution of BioAtla’s current and future product and strategic plans. The proceeds of this financing greatly enhance our ability to design, implement, and execute clinical programs evolving from our CAB platform that uniquely yields tumor-targeting antibodies with the potential for an enhanced benefit risk profile” said Jay M. Short, Ph.D., chairman and chief executive officer of BioAtla. “We look forward to driving Phase 2 trials addressing high unmet medical needs in oncology for our innovative CAB-AXL-ADC (BA3011) and CAB-ROR2-ADC (BA3021) product programs, as well as advancing clinical studies for CAB-CTLA-4 (BA3071),” stated Scott Smith, president of BioAtla. “In addition, we are pursuing development of several T cell-recruiting CAB-bispecific candidates.”

 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 BioAtla, Inc.

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). BioAtla’s investigational CAB CTLA-4 antibody, BA3071, is subject of a global co-development and collaboration agreement with BeiGene Ltd. for its development, manufacturing and commercialization. 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 anti-PD-1 antibody, tislelizumab.

 

 

 

# # #

Contact:

Richard Waldron

Chief Financial Officer

BioAtla, Inc

rwaldron@bioatla.com

858.356.8945

BIOATLA APPOINTS ERIC SIEVERS, M.D., AS CHIEF MEDICAL OFFICER

Experienced leader of oncology clinical trial approvals to head BioAtla’s clinical development programs


SAN DIEGO, CA
– June 28, 2019 - BioAtla, LLC, a global biotechnology company focused on the development of Conditionally Active Biologic (CAB) antibody therapeutics, today announced the appointment of Eric L. Sievers, M.D., as chief medical officer.  Dr. Sievers, an experienced biotechnology drug developer in oncology, joins the Company bringing clinical development and management experience directly relevant to BioAtla’s oncology focus and pipeline of Conditionally Active Biologic (CAB) candidates including in immuno-oncology and antibody drug conjugates (ADCs). His clinical development leadership, design and execution resulted in several successful oncology registration trials and approvals including, for Seattle Genetics, approvals of ADCETRIS in Hodgkin lymphoma, in peripheral T-cell lymphoma, and in cutaneous T-cell lymphoma. 

 

“Dr. Sievers’ experience and proven capabilities in leading the clinical development of innovative oncology products greatly enhances BioAtla’s ability to design, implement, and execute clinical programs evolving from our CAB platform that uniquely yields tumor-targeting antibodies with high safety” said Jay M. Short, Ph.D., chairman and chief executive officer of BioAtla. “Dr. Sievers’ knowledge of and background in developing advanced biologics including ADC’s, and his experience in leading partnership interactions with pharmaceutical company partners is directly applicable to our current and future product and strategic plans,” stated Scott Smith, president of BioAtla.

 

About Dr. Sievers

Dr. Sievers joins BioAtla with over 25 years of clinical and translational biomedical research experience in multiple settings, including biotechnology industry, hospital- and clinic-based clinical practice and academics. During his nine years at Seattle Genetics, he was closely involved with the development and regulatory approval of ADCETRIS (brentuximab vedotin), an ADC.  Serving in multiple roles of increasing leadership responsibility, he led the Seattle Genetics clinical team and Takeda (Millennium) development partner to design, initiate and enroll four randomized Phase 3 registration trials for ADCETRIS that each ultimately resulted in new indications approved by the FDA. Dr. Sievers has managed clinical development efforts from Phase 1 to Phase 3 clinical trials, from strategy planning to study execution and BLA/NDA submissions. Prior to his career at Seattle Genetics, Dr. Sievers was Medical Director at ZymoGenetics where he designed and supervised clinical trials of recombinant human interleukin 21 and TACI-Fc5 for patients with cancer and evaluated new oncology opportunities.  Before then, he was with the Fred Hutchinson Cancer Research Center for 12 years where he attained the position of Assistant Member and was Assistant Professor of Pediatrics at the University of Washington. During this time, he served as the lead investigator of Phase 1 and pivotal trials that resulted in the approval of an antibody drug conjugate MYLOTARG® indicated for patients with acute myeloid leukemia. Dr. Sievers’ most recent position was Chief Medical Officer at Trillium Therapeutics where he developed clinical trial strategies and oversaw all clinical development employing a decoy receptor to block the CD47 “do not eat” signal overexpressed by cancer cells.  Dr. Sievers received both his medical degree and his B.A. degree from Brown University.

 

 

 

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 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).

 

Learn more at www.bioatla.com.

 

# # #

Contact:


Richard Waldron

Chief Financial Officer

BioAtla, LLC

rwaldron@bioatla.com

858.356.8945

BIOATLA SUBSIDIARY, HIMALAYA THERAPEUTICS, WILL DEVELOP AND COMMERCIALIZE CAB PRODUCTS IN GREATER CHINA MARKET

First Conditionally Active Biologics licensing participation in Greater China territory

San Diego, CA
– April 16, 2019 - BioAtla®, LLC, a global clinical-stage biotechnology company focused on the development of Conditionally Active Biologic (CAB) protein therapeutics for the oncology market, today announced that Himalaya Therapeutics SEZC, a Cayman Island corporation and majority owned subsidiary of BioAtla, has the exclusive license from BioAtla to develop and commercialize several specific, differentiated product candidates for the Greater China market of the PRC, Hong Kong, Macau and Taiwan. The Himalaya Therapeutics portfolio includes two CAB candidates, CAB-AXL-ADC and CAB-ROR2-ADC, each currently in Phase 1/2 clinical trials conducted by BioAtla at sites in the United States. In addition, Himalaya Therapeutics will participate in BioAtla’s potential Greater China derived returns from the recently announced BioAtla and BeiGene, Ltd. global co-development and collaboration agreement for the development, manufacture and commercialization of CAB-CTLA-4 (BA3071).  Himalaya will also support Bioatla’s global clinical trials effort in Greater China.  

“We believe that Himalaya’s product development and business related activities directly addressing Greater China will maximize the strategic opportunities for both BioAtla and Himalaya in the world’s second largest pharmaceutical market,” stated Carolyn Short, General Manager of Himalaya Therapeutics. “The access to clinical development capabilities in China can accelerate the global development and potential commercialization of the BioAtla product portfolio and effectively address markets with strong growth potential and high unmet medical need,” added Scott Smith, President of BioAtla.

Recent sweeping changes to the China regulatory processes for the development of pharmaceutical products now closely align them with those in the United States and broadens the use of clinical data for regulatory purposes between the two nations.  Consequently, close coordination of clinical development in the U.S. and China of a pharmaceutical candidate is highly desireable and more efficient.  Furthermore, the access to capital markets for early-stage biotechnology companies in China has recently been greatly enhanced especially with the revision to the stock listing requirements on the Hong Kong Stock Exchange. Himalaya Therapeutics is expected to fund its operations independent from BioAtla.  These were primary motivating factors for Beijing Sinobioway Group Company and its related investor groups to contribute all of their rights to certain and any future CAB candidates that were part of their 2015 collaboration agreement with BioAtla in exchange for a minority equity position in Himalaya Therapeutics.   

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 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).

 

Contact:

Richard Waldron

Chief Financial Officer BioAtla, LLC rwaldron@bioatla.com 858.356.8945

BIOATLA AND BEIGENE FORM WORLDWIDE COLLABORATION TO DEVELOP AND COMMERCIALIZE NOVEL CONDITIONALLY ACTIVE BIOLOGIC CTLA-4 THERAPY


Plan to pursue development as a monotherapy and in combination with BeiGene’s investigational anti-PD-1 antibody, tislelizumab

 

San Diego, CA; Beijing, China and Cambridge, MA,  – April 8, 2019 – 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.

 


BeiGene Investor Contact
Craig West
+1 857-302-5189
ir@beigene.com 

 

BeiGene Media Contact
Liza Heapes
+1 857-302-5663 
media@beigene.com


 

BioAtla Contact:

Richard Waldron

Chief Financial Officer

BioAtla, LLC

rwaldron@bioatla.com

858-356-8945

 

1 ABRAXANE®, REVLIMID®, and VIDAZA® are registered trademarks of Celgene Corporation.

 

BIOATLA PRESENTS CAB-CTLA-4 AND CAB-EpCAM-ADC DATA AT THE AMERICAN ASSOCIATION FOR CANCER RESEARCH ANNUAL MEETING

Oral presentation highlights CAB-CTLA-4 pre-clinical data demonstrating expected efficacy and reduced immune side effects and toxicities as monotherapy or in combination with PD-1 inhibitors

 

Poster presentation of CAB-EpCAM-ADC demonstrating anti-tumor efficacy in vivo

 

San Diego, CA – February 27, 2019 - BioAtla ®, LLC, a global clinical-stage biotechnology company focused on the development of Conditionally Active Biologic (CAB) protein therapeutics, will present pre-clinical data on BA3071 and BA3181, the company’s novel CAB-CTLA-4 and CAB-EpCAM-ADC programs, at the 2019 American Association For Cancer Research (AACR) annual meeting in Atlanta, Georgia on March 29-April 3, 2019.

“These new data showcase the capabilities of our proprietary CAB technology, which we believe will expand the number of druggable protein targets and maximize both potency and safety in combination therapies, antibody drug conjugate (ADC) medicines, bispecifics and other targeted therapy formats for cancer treatments,” stated Jay M. Short, Ph.D., Chairman, CEO and co-founder of BioAtla.

"We are particularly excited by these new preclinical data for our novel CAB-CTLA-4 program as a single-agent or in combination with checkpoint inhibitors. This novel CAB has the potential for an improved safety margin and therapeutic index thereby improving this important cancer therapy," said Scott Smith, President of BioAtla.

“These preclinical data suggest that our CAB technology may effectively address the issue of on-target off-tumor toxicity and allow leveraging the widely expressed and promising EpCAM target for cancer therapy,” added Scott Smith.

BA3071 is a novel conditionally active CTLA-4 inhibitor. The CTLA-4 pathway is a key immune checkpoint pathway that provides a downregulating signal to T cells. Although inhibition of CTLA-4 has been shown to significantly improve the antitumor response, it may also lead to immune attack of healthy cells. To minimize on-target off-tumor toxicity, BioAtla applies its proprietary CAB technology with the intent to activate binding to the CTLA-4 receptor preferentially on T cells in the tumor microenvironment. The data to be presented at AACR indicate that our CAB-CTLA-4 molecule may have a superior safety profile when used in combination with PD-1 inhibitors and allow increased dosing levels to achieve superior efficacy to current anti-CTLA-4 therapy as a single agent or in combination with other anti-cancer therapies including immuno-oncology agents. The BA3071 IND filing is planned for mid-2019. 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 a PD-1 inhibitor is anticipated to start in H2 2019.

BA3181 is a novel conditionally active EpCAM targeted antibody drug conjugate (CAB-EpCAM-ADC). EpCAM is expressed at high levels exclusively in epithelia and epithelial-derived neoplasms, making it a suitable target for many important solid tumor types and cancer stem cells. EpCAM expression on normal tissues limits its utility as a target for therapeutic antibodies and ADCs due to the potential effects on normal epithelial throughout the body. Using our CAB technology, BioAtla has developed CAB antibodies to EpCAM that reversibly bind to recombinant EpCAM and EpCAM expressing cells under select conditions that are present in the tumor microenvironment but not in normal tissues. In vitro and in vivo efficacy data for several anti-EpCAM antibodies and ADCs will be presented and suggest that conditionally active EpCAM ADCs generated using the CAB technology provided drug candidates, including BA3181, that have the potential to have an increased safety margin and therapeutic index in the clinic. 

Abstract Selected for Oral Presentation:

19-A-6330-AACR:  Potent CAB CTLA-4 antibody to reduce immune side effects and toxicities associated with single agent and combination cancer immuno therapies

Abstract Control Number: 6215

Session Title:  Rational Combinations of Immunotherapy

Session Date and Time: 4/1/2019 3:00PM - 5:00 PM

Presenter:  William Boyle, Ph.D., Chief of Translational Medicine, BioAtla LLC

Abstract Selected for Poster Presentation

Novel conditionally active biologic (CAB) antibody targeting EpCAM demonstrates anti-tumor efficacy in vivo

Session Title:  New Anticancer Agents

Session Date and Time:   Sunday Mar 31, 2019 1:00 PM - 5:00 PM

Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 14

Poster Board Number:  17

Permanent Abstract Number: 356 

Session information is available online via the Annual Meeting Itinerary Planner through the AACR website at www.aacr.org.

About Conditionally Active Biologics (CABs)

Conditionally Active Biologic proteins are 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, 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 tumor microenvironments (TMEs) are primarily influenced by the characteristic glycolytic metabolism associated with cancer cells, including for those cells under aerobic conditions referred to as the Warburg Effect. 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, thereby widening the therapeutic index. 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 BioAtla , LLC

BioAtla is a global clinical-stage biotechnology company headquartered in San Diego, California, and with operations in 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 US, 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), in addition to two licensed, royalty-bearing clinical stage CAB programs.

 

Contact:

Richard Waldron

Chief Financial Officer

BioAtla, LLC

rwaldron@bioatla.com

858.356.8945

 

BIOATLA CONGRATULATES JAMES ALLISON, PH.D. FOR RECEIVING NOBEL PRIZE

Drs. Allison and Sharma advising BioAtla on its CAB-CTLA4 antibody drug candidate and other proprietary CAB programs and the design of combination therapies

 

SAN DIEGO, CA – October 4, 2018 - BioAtla, LLC, a global biotechnology company focused on the development of Conditionally Active Biologic (CAB) antibody therapeutics, congratulates James Allison, Ph.D., for receiving the 2018 Nobel Prize in Physiology or Medicine recognizing his leading role in launching an effective new way to attack cancer by treating the immune system. Dr. Allison and Padmanee Sharma, M.D., Ph.D., both at MD Anderson and leading researchers in the field of immuno-oncology, are scientific advisors to BioAtla. Dr. Allison’s pioneering research in the regulation of T cell responses and strategies for cancer immunotherapy led to the development of the ipilimumab antibody to CTLA-4, the first immune checkpoint blockade therapy approved by the U.S. Food and Drug Administration. 

 

“We congratulate Jim for receiving the world’s preeminent award for outstanding discoveries in the field of life sciences and medicine,” said Jay M. Short, Ph.D., Chairman, Chief Executive Officer and co-founder of BioAtla. “As scientific advisors to BioAtla, he and Dr. Sharma provide valuable contributions to the direction and prioritization of our CAB development programs, including our CAB-CTLA4 antibody candidate, and to enhance our decisions and design of combination CAB immunotherapies and CAB bispecifics,”

 

About Dr. Allison

James Allison, Ph.D., is Chair of the Department of Immunology, the Vivian L. Smith Distinguished Chair in Immunology, Director of the Parker Institute for Cancer Research, and the Executive Director of the Immunotherapy Platform at The University of Texas MD Anderson Cancer Center (MD Anderson).

 

Among Dr. Allison’s most notable discoveries in his distinguished career studying the regulation of T cell responses, are the determination of the T cell receptor structure and that CD28 is the costimulatory molecule that allows full activation of naïve T cells and prevents anergy in T cell clones.  His lab resolved a major controversy by demonstrating that CTLA-4 inhibits T cell activation by opposing CD28-mediated costimulation and that blockade of CTLA-4 could enhance T cell responses, leading to tumor rejection in animal models, and launched the emerging field of immune checkpoint blockade therapy for cancer. Dr. Allison is a member of the National Academies of Science and Medicine.  In addition to recently receiving the Nobel Prize, he received the Lasker-Debakey Clinical Medical Research Award in 2015.

 

About Conditionally Active Biologics (CABs)

Conditionally Active Biologic proteins are generated using BioAtla’s proprietary protein discovery, evolution and expression technologies. These proteins can be antibodies, enzymes and other proteins designed with functions dependent on changes in microphysiological 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. 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 monoclonal antibodies (mAbs), antibody drug conjugates (ADCs), bi-specifics, chimeric antigen receptor T-cells (CAR-Ts) and combination therapies.

 

About BioAtla, LLC

BioAtla is a global 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. Two of the Company’s conditionally active drug candidates, BA3011, an AXL-targeted antibody-drug conjugate (CAB-AXL-ADC), and BA3021, a ROR2-targeted antibody-drug conjugate (CAB-ROR2-ADC), currently are each the subject of a multi-center, open-label, Phase 1/2 study designed to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and antitumor activity of the CAB candidate in patients with advanced solid tumors. In addition, two licensed CAB CAR-T antibodies are in clinical trials for solid tumors in China.

 

Learn more at www.bioatla.com.

 

 

Contact:
Richard Waldron

Chief Financial Officer

BioAtla, LLC

rwaldron@bioatla.com

858.356.8945

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