Shattuck Labs Announces Oral Presentation of Preclinical Data at the American Association for Cancer Research (AACR) Annual Meeting 2024
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Insights
The revelation of TRIM7 as a key driver in immune checkpoint blockade (ICB) acquired resistance presents a significant stride in the oncology field. The ability to reverse acquired resistance to PD-1/L1 therapies could potentially expand treatment options for patients who have developed resistance to current immunotherapies. As an oncology research analyst, the focus on the ubiquitination pathways, specifically through TRIM7's stabilization of RACO-1 and degradation of STING and MAVS, is a noteworthy approach. This mechanism is particularly intriguing as it offers a targeted strategy to address the resistance issue, rather than a broad-spectrum method.
Shattuck Labs' development of small-molecule inhibitors that can restore sensitivity to PD-1 therapy in resistant tumors could be a game-changer for cancer treatment regimens. If these preclinical results translate into human trials, the company could see a significant increase in their oncology pipeline's value. Investors should monitor the progression of these compounds through clinical trials, as successful outcomes could lead to substantial market opportunities and partnerships.
From a market perspective, Shattuck Labs' announcement is likely to attract investor attention due to the high demand for effective treatments in oncology, particularly concerning drug resistance. The identification of TRIM7 as a novel target and the subsequent development of inhibitors could position Shattuck as a pioneer in a niche but critical area of cancer therapeutics. The preclinical data's presentation at a prestigious conference such as AACR increases the visibility of Shattuck's research endeavors and its potential impact on the market.
Considering the extensive application of PD-1/PD-L1 inhibitors across multiple tumor types, the therapeutic utility of TRIM7 inhibition could have wide-ranging implications. It is essential, however, to remain cautious as the transition from preclinical to clinical efficacy is not guaranteed and the actual impact on the company's financials will depend on clinical trial outcomes, regulatory approvals and market adoption. Investors should assess the risks associated with the development stage of the compound while acknowledging the potential for high returns if the inhibitor successfully navigates the regulatory pathway.
Shattuck Labs' focus on bifunctional fusion proteins and the expansion of their oncology pipeline through the development of TRIM7 inhibitors is indicative of the innovative approaches being pursued in drug development. The specificity of TRIM7 inhibitors in targeting the ubiquitination pathway is a sophisticated strategy that may offer fewer side effects and improved outcomes compared to broader treatments. This precision medicine approach is reflective of the industry's shift towards targeted therapies, which are designed to improve patient outcomes by honing in on specific molecular targets.
The potential to reverse PD-1 acquired resistance could lead to improved durability of response for patients, which is a significant concern in current cancer treatments. The long-term implications for patients could include prolonged survival rates and a better quality of life. As this compound moves into clinical trials, the pharmaceutical development landscape will closely watch for its safety profile and efficacy data, which will be important for its eventual market success.
– Aberrant TRIM7 expression identified as a key driver of immune checkpoint blockade (ICB) acquired resistance; inhibition of TRIM7 with small molecule inhibitors may prevent or reverse acquired resistance to PD-1/L1 blockade –
AUSTIN, TX and DURHAM, NC, April 09, 2024 (GLOBE NEWSWIRE) -- Shattuck Labs, Inc. (Shattuck) (Nasdaq: STTK), a clinical-stage biotechnology company pioneering the development of bifunctional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease, today announced preclinical data demonstrating the therapeutic utility of TRIM7 inhibition to prevent or reverse acquired resistance to immune checkpoint therapy. These data were featured in an oral presentation during the AACR Annual Meeting 2024, being held from April 5-10, 2024, in San Diego, California.
“One of the largest areas of unmet medical need in oncology is in the setting of acquired resistance to checkpoint inhibitors, and we expect this to continue to grow because of the broad application of anti-PD1/PD-L1 inhibitors across multiple tumor types. Our efforts in helping to define the underlying biology of acquired resistance were recently revealed with a publication in Cancer Cell,” said Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. “I am very pleased to share how our team has leveraged those biological insights to identify a novel target, TRIM7, which appears to be a mediator of the acquired resistant phenotype in mouse and human tumors, and, importantly, this has led to a development compound that reverses PD-1 acquired resistance in pre-clinical studies through specific inhibition of TRIM7. We expect that these efforts will support expansion of our oncology pipeline alongside our lead program, SL-172154.”
Presentation Details
Abstract title: Aberrant TRIM7 Expression Potentiates RACO-1 Mediated Proliferation and Dysregulated Interferon Responsiveness in the Setting of anti-PD-1 Acquired Resistance in Cancer
Location: San Diego Convention Center, San Diego, California
Presenter: Dr. George Fromm, Ph.D., Chief Scientific Officer, Shattuck Labs
Session Category: Experimental and Molecular Therapeutics
Session Title: Drug Discovery 2: New Therapies
Date/Time: Tuesday, April 9, 2024, 4:05 PM - 4:20 PM (PT)
Abstract Presentation Number: 6584
Key Takeaways
- TRIM7 is an E3 ligase which supports tumor cell proliferation downstream of KRAS signaling through ubiquitination and stabilization of RACO-1. TRIM7 also contributes to PD-1 acquired resistance through ubiquitination and degradation of STING and MAVS.
- Shattuck developed a series of small-molecule inhibitors of TRIM7 that specifically disrupt KRAS-mediated tumor cell proliferation, reverse the transcriptional phenotype of PD-1 acquired resistance, and restore sensitivity to anti-PD1 antibodies to PD-1 acquired resistant tumors in pre-clinical models.
Additional meeting information can be found on the AACR website. A copy of the AACR presentation will be available on the Investors section of the Company’s website shortly after the event.
About Shattuck Labs, Inc.
Shattuck Labs, Inc. (Nasdaq: STTK) is a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease. Compounds derived from Shattuck’s proprietary Agonist Redirected Checkpoint (ARC®) platform are designed to simultaneously inhibit checkpoint molecules and activate costimulatory molecules with a single therapeutic. The company’s lead SL-172154 (SIRPα-Fc-CD40L) program, which is designed to block the CD47 immune checkpoint and simultaneously agonize the CD40 pathway, is being evaluated in multiple Phase 1 trials. Shattuck has offices in both Austin, Texas and Durham, North Carolina. For more information, please visit: www.ShattuckLabs.com.
Forward-Looking Statements
Certain statements in this press release may constitute “forward-looking statements” within the meaning of the federal securities laws, including, but not limited to, statements regarding: the potential benefit of TRIM7 inhibition alone or in combination with KRAS pathway inhibition and/or blockage of PD-L1, clinical development plans and strategies for SL-172154, future plans for Shattuck’s pipeline and Shattuck’s strategies. Words such as “anticipate,” “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “design,” “estimate,” “predict,” “potential,” “develop,” “plan” or the negative of these terms, and similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. While the company believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to the company on the date of this release. These forward-looking statements are based upon current estimates and assumptions and are subject to various risks and uncertainties (including, without limitation, those set forth in Shattuck’s filings with the U.S. Securities and Exchange Commission (SEC)), many of which are beyond the company’s control and subject to change. Actual results could be materially different. Risks and uncertainties which could cause such outcomes to change include: global macroeconomic conditions and related volatility; expectations regarding the initiation, progress, and expected results of Shattuck’s preclinical studies, clinical trials and research and development programs; expectations regarding the timing, completion and outcome of the company’s clinical trials; the unpredictable relationship between preclinical study results and clinical study results; the timing or likelihood of regulatory filings and approvals; liquidity and capital resources and other risks and uncertainties identified in Shattuck’s Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent disclosure documents filed with the SEC. Shattuck claims the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. Shattuck expressly disclaims any obligation to update or alter any statements whether as a result of new information, future events or otherwise, except as required by law.
The Company intends to use the investor relations portion of its website as a means of disclosing material non-public information and for complying with disclosure obligations under Regulation FD.
Investor & Media Contact:
Conor Richardson
Vice President of Investor Relations
Shattuck Labs, Inc.
InvestorRelations@shattucklabs.com
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