Twist Bioscience Publishes Preclinical Data Detailing Discovery of Antibody Targeting Emerging Checkpoint Inhibitor
Twist Bioscience (NASDAQ: TWST) has announced the discovery of TB206-001, a first-in-class antibody targeting the adenosine A2A receptor (A2AR), which could enhance cancer immunotherapy. The preclinical study, published in PLOS ONE, shows that TB206-001 has high affinity and tumor-suppressing activity, especially in colon tumor-bearing HuCD34-NCG mice, outperforming PD-1 inhibitors. The antibody targets GPCRs, common in immune cells and certain cancers, and works by blocking A2AR, thereby activating immune cells. Twist Bioscience is offering TB206-001 for out-licensing, indicating its potential for further clinical development.
- TB206-001 shows high affinity for A2AR, suggesting strong efficacy
- Preclinical studies indicate TB206-001 reduces tumor volume better than PD-1 inhibitors
- TB206-001 targets GPCRs, a promising class of therapeutic targets
- The antibody has tumor-suppressing activity in colon tumor-bearing HuCD34-NCG mice
- Twist Bioscience is offering TB206-001 for out-licensing, opening opportunities for partnerships
- The study is still in preclinical stages, indicating that results may not translate to human trials
- High development costs for antibody therapies could present a financial risk
- Potential challenges in finding a suitable partner for out-licensing
Insights
The discovery of TB206-001, an antibody targeting the A2A receptor, represents a significant advancement in cancer immunotherapy. Current therapies primarily focus on small molecules, which, while effective, often have limitations in terms of specificity and dosing frequency. Antibodies, on the other hand, offer higher target affinity and reduced dosing needs. A2AR is a compelling target because it's involved in immunosuppression within tumor environments common in various cancers including colorectal, gastric, breast cancer and melanoma.
From a clinical perspective, the potential of TB206-001 to restore immune responses by blocking A2AR could revolutionize treatment strategies. The preclinical data showing better tumor volume reduction compared to PD-1 inhibitors is particularly promising. This could lead to improved patient outcomes, especially in cancers that have shown resistance to current treatments.
However, it's essential to consider that preclinical success does not always translate to clinical success. More comprehensive clinical trials will be needed to confirm the efficacy and safety of TB206-001 in humans.
Twist Bioscience's announcement about TB206-001 holds strong implications for the market. The publication in PLOS ONE and the positive preclinical results suggest a promising pipeline addition, which could attract partnerships and out-licensing opportunities. The ability of TB206-001 to potentially outperform PD-1 inhibitors in reducing tumor volume in preclinical studies speaks to its market potential.
From an investment standpoint, this discovery could enhance Twist Bioscience's value proposition. Licensing the antibody to a pharmaceutical partner could provide substantial revenue streams without the need for costly late-stage clinical development. Investors should watch for updates on licensing deals or partnerships, which could drive stock performance.
Nevertheless, the transition from preclinical to clinical development is fraught with risks. Investors should remain cautious and look for further milestones that demonstrate the antibody's continued promise.
Financially, the development of TB206-001 represents both an opportunity and a risk for Twist Bioscience. The potential for out-licensing the antibody offers a pathway to monetization without the firm having to bear the full brunt of clinical development costs. This approach can be financially prudent, allowing Twist to focus on its core business while reaping the benefits of its research advancements.
However, investors must be cognizant of the inherent uncertainties in the biotech sector. The success of TB206-001 in preclinical models is promising, but the financial impact will largely depend on securing a development partner and the outcomes of future clinical trials. Any delays or negative results could adversely affect stock price and investor sentiment.
On the positive side, partnering with a major pharmaceutical company could provide not just financial backing but also validation of Twist's technology and approach, potentially boosting investor confidence and stock valuation.
TB206-001 shown to be a high-affinity, cross-reactive humanized antibody antagonist of A2AR with in vivo tumor suppressing activity
TB206-001 available for out-licensing
A2AR is an emerging immune checkpoint that plays a role in the immunosuppression of the tumor microenvironment. It is part of an important class of therapeutic targets, called G protein-coupled receptors (GPCRs), which are found on most immune cells and highly expressed in certain cancers. Tumors commonly produce excess adenosine, which activates A2A receptors and suppresses immune cells. Blocking A2AR could alleviate the suppressive environment and restore tumor immunity. A2AR has been shown to play a role in various cancers including colorectal cancer, gastric cancer, lymph node metastasis, breast cancer and melanoma as well as in autoimmune diseases and Parkinson’s.
“The majority of current therapies in clinical trials targeting A2AR are small molecules, as it has been traditionally difficult to discover antibodies that block GPCRs; however, antibodies have greater affinity for target molecules, do not cross into the central nervous system and could be dosed less frequently,” said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience. “With the right partner to take it forward, TB206-001, our Twist-discovered first-in-class antibody antagonist of A2AR, could be developed as a powerful inhibitor to restore immune responses in immunosuppressive environments that allow cancer to grow.”
In the study, the researchers immunized two different sets of animals with DNA encoding wildtype or mutant hA2AR (C144S, S334A, S338A) modified to minimize the impact of the receptor’s natural signaling on its expression. Once the animals generated antibodies to the receptor, the researchers built immune and synthetic single-chain variable fragment (scFvs) phage display libraries from the immune repertoire. The libraries were subsequently screened against detergent solubilized A2AR, and positive hits were reformatted into monoclonal antibodies for further testing. The result was TB206-001, which directly targets A2AR and activates immune cells. In preclinical studies, the antibody has shown high affinity and specific activity for A2AR over other adenosine receptors and shows tumor-suppressing activity in colon tumor-bearing HuCD34-NCG mice. Additional studies in animal models found that TB206-001 reduced tumor volume better than PD-1 inhibitors.
“There is still tremendous potential for immunotherapies either in combination with or in addition to those targeting PD-1 and CLTA-4,” said Gregory Carven, Ph.D., one of the original inventors of Keytruda. “Using the ability to create large antibody libraries enabling discovery of novel and highly specific therapeutics, Twist has discovered an antibody that blocks A2AR, a promising checkpoint target and demonstrated its activity in preclinical models. The antibody could be further developed as a standalone therapy, bispecific or combination therapy to bring potential therapeutic benefit to patients.”
About Twist Bioscience Corporation
Twist Bioscience is a leading and rapidly growing synthetic biology and genomics company that has developed a disruptive DNA synthesis platform to industrialize the engineering of biology. The core of the platform is a proprietary technology that pioneers a new method of manufacturing synthetic DNA by “writing” DNA on a silicon chip. Twist is leveraging its unique technology to manufacture a broad range of synthetic DNA-based products, including synthetic genes, tools for next-generation sequencing (NGS) preparation, and antibody libraries for drug discovery and development. Twist is also pursuing longer-term opportunities in digital data storage in DNA and biologics drug discovery. Twist makes products for use across many industries including healthcare, industrial chemicals, agriculture and academic research.
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Twist Bioscience Legal Notice Regarding Forward-Looking Statements
This press release contains forward-looking statements. All statements other than statements of historical facts contained herein are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including statements regarding the ability of TB206-001 to enhance cancer immunotherapy. Forward-looking statements involve known and unknown risks, uncertainties, and other important factors that may cause Twist Bioscience’s actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the ability to achieve the expected benefits of Twist Bioscience’s restructuring activities and reduced investments in DNA data storage; the ability to attract new customers and retain and grow sales from existing customers; the ability of Twist Bioscience to achieve sufficient revenue to achieve or maintain positive cash flow from operations or profitability in any given period will depend heavily on the success of our existing products and the development and commercialization of additional products in the synthetic biology, biologic drug and data storage industries; risks and uncertainties of rapidly changing technologies and extensive competition in synthetic biology that could make the products Twist Bioscience is developing obsolete or non-competitive; uncertainties of the retention of significant customers; the ability of Twist Bioscience to successfully integrate acquired companies and to achieve expected benefits from acquisitions; supply chain and other disruptions; risks of third party claims alleging infringement of patents and proprietary rights or seeking to invalidate Twist Bioscience’s patents or proprietary rights; and the risk that Twist Bioscience’s proprietary rights may be insufficient to protect its technologies. For a description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Twist Bioscience’s business in general, see Twist Bioscience’s risk factors set forth in Twist Bioscience’s Annual Report on Form 10-K filed with the SEC on November 21, 2023 and subsequent filings with the SEC. Any forward-looking statements contained in this press release speak only as of the date hereof, and Twist Bioscience specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.
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