Shattuck Labs to Present Additional Data from the Phase 1B Dose Expansion Clinical Trial of SL-172154 with Azacitidine (AZA) in Frontline Higher-Risk Myelodysplastic Syndromes (HR-MDS) and TP53 mutant (TP53m) Acute Myeloid Leukemia (AML) Patients at the European Hematology Association (EHA) 2024 Congress
Shattuck Labs (Nasdaq: STTK) will present new data from its Phase 1B trial of SL-172154 at the European Hematology Association (EHA) 2024 Congress. The trial, which combines SL-172154 with azacitidine (AZA), targets frontline higher-risk myelodysplastic syndromes (HR-MDS) and TP53 mutant (TP53m) acute myeloid leukemia (AML). As of February 1, 2024, the combination therapy showed promising complete response (CR) rates and an acceptable safety profile. The HR-MDS cohort had a 65% objective response rate (ORR), while TP53m AML had a 36% ORR. The next data update is expected in the second quarter of 2024. Key safety concerns include infusion-related reactions and some severe treatment-emergent adverse events (TEAEs).
- HR-MDS cohort showed a 65% objective response rate (ORR).
- TP53m AML cohort achieved a 36% ORR.
- Combination therapy demonstrated an acceptable safety profile.
- No progression observed in patients who achieved a complete response (CR).
- Some patients successfully bridged to hematopoietic cell transplantation (HCT).
- Additional data to be presented at EHA 2024 Congress.
- 18 patients (46%) reported infusion-related reactions (IRRs), with two being Grade 3.
- 11 patients (28%) experienced Grade 3/4 SL-172154 related TEAEs, including fatigue, febrile neutropenia, and IRR.
- Two patients had drug discontinuations due to severe adverse events: one Grade 4 myocardial infarction and one Grade 5 cardiac arrest.
- Both severe TEAEs occurred in patients with significant cardiovascular history and comorbidities.
Insights
The interim data from the Phase 1B clinical trial for SL-172154 in combination with Azacitidine (AZA) for frontline Higher-Risk Myelodysplastic Syndromes (HR-MDS) and TP53 mutant (TP53m) Acute Myeloid Leukemia (AML) patients appears quite promising. The 65% objective response rate (ORR) in HR-MDS patients and a 36% ORR in TP53m AML patients signal potential efficacy, particularly in a challenging patient population. The fact that none of the patients with a complete response (CR) had progressed as of the data cutoff is a significant positive point, as it suggests durability of response.
The role of TP53 mutations in AML and HR-MDS is well-documented and these patients usually have a poor prognosis with conventional treatments. Hence, new therapies that show potential efficacy in this subset are critically important. However, it's important to bear in mind that these results are still preliminary. Long-term data on overall survival and the duration of response will ultimately determine the true clinical value of SL-172154.
From a safety perspective, the profile seems acceptable with most treatment-emergent adverse events being Grade 1 or 2. The observed Grade 3 and 4 events and two drug discontinuations due to severe adverse events warrant careful monitoring going forward.
Overall, the data thus far is encouraging but needs further validation.
Shattuck Labs' presentation of additional data from their Phase 1B trial for SL-172154 at the European Hematology Association (EHA) Congress highlights their ongoing efforts to demonstrate the drug's efficacy and safety. The 65% ORR in HR-MDS and the successful bridging of TP53m AML patients to hematopoietic cell transplantation (HCT) are noteworthy, as these metrics often indicate meaningful clinical benefit in difficult-to-treat populations.
The decision to expand both cohorts after initial enrollment suggests confidence in the drug's potential and a strategic move to gather more data. However, the data cutoff on February 1, 2024, means the results are still early and more mature data will be necessary to fully assess the therapeutic potential. Investors should look out for the next planned data cutoff in late Q2 2024 for more comprehensive insights.
The safety profile, while acceptable, does indicate some significant adverse events, including infusion-related reactions and cytokine release syndrome, which are common in immunotherapy treatments. The Grade 4 myocardial infarction and Grade 5 cardiac arrest, though possibly related to underlying conditions, are concerning and must be closely monitored in future studies.
For investors, the potential of SL-172154 looks promising but still requires cautious optimism given the early stage.
From a financial perspective, the announcement of encouraging clinical data for SL-172154 in combination with Azacitidine could drive positive sentiment around Shattuck Labs' stock (Nasdaq: STTK). The relatively high response rates in HR-MDS and TP53m AML patients indicate a significant market opportunity, particularly given the limited treatment options available for these conditions.
However, it's important to understand that these results are from an early-phase trial. The future financial impact will hinge on the outcomes of later-phase studies, regulatory approvals and successful commercialization. Investors should monitor updates closely, especially the additional data expected in late Q2 2024, which might provide a clearer picture of the drug's potential impact on Shattuck's revenue streams.
Shattuck's strategy to present this data at the EHA Congress is a smart move, as it allows them to showcase their progress to a broad audience of hematology experts and potential partners. This exposure could open doors for future collaborations or licensing deals, which can be important for funding subsequent trial phases and eventual market entry.
In the short term, the news might have a positive effect on Shattuck's stock price, but a long-term outlook will need a cautious approach until more comprehensive data confirm the drug's efficacy and safety.
– Observed encouraging complete response (CR) rates as of the February 1, 2024, data cutoff in previously untreated HR-MDS and TP53m AML patients; successfully bridged responding TP53m AML patients to hematopoietic cell transplantation –
– SL-172154 continued to demonstrate an acceptable safety profile in combination with AZA –
– EHA poster presentation to include additional data from the next planned data cutoff in the second quarter of 2024 –
AUSTIN, TX and DURHAM, NC, May 14, 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 the presentation of additional data from the Phase 1B dose expansion clinical trial of SL-172154 with AZA in frontline HR-MDS and TP53m AML patients. These data will be featured in a poster presentation at the EHA 2024 Congress, being held June 13-16, 2024, both virtually and in Madrid, Spain.
“We are rapidly progressing in our clinical development of SL-172154. After completing initial enrollment in the fourth quarter of 2023, we elected to expand both the frontline HR-MDS and TP53m AML cohorts this year,” said Dr. Lini Pandite, MBChB, M.B.A., Chief Medical Officer of Shattuck. “The complete response rate in HR-MDS increased by the February 1st data cutoff, and the ORR increased in the TP53m AML cohort. This is encouraging because many patients were still early in their course of treatment. With the next planned data cutoff in the late second quarter of 2024, we are well positioned to provide an update at the EHA Annual Congress. We believe these data will further underscore the therapeutic potential of SL-172154 for patients with previously untreated HR-MDS and TP53m AML.”
The full abstract (#P773) is accessible on the EHA Congress portal, and additional details are provided below.
- Title: Phase 1B Study of SL-172154, a Bi-functional Fusion Protein Targeting CD47 and CD40, with Azacitidine in Previously Untreated Acute Myeloid Leukemia and Higher-Risk Myelodysplastic Syndromes
- Presenter: Dr. Amer Zeidan
- Format: Poster Presentation
- Date and Time: June 14th at 18:00 CEST
Key Takeaways from Phase 1B Trial of SL-172154 in Frontline HR-MDS and TP53m AML
Key takeaways: Interim efficacy as of February 1, 2024 observed for SL-172154 in combination with AZA in frontline HR-MDS and TP53m AML. EHA poster presentation to include additional data from the next planned cutoff in the second quarter of 2024.
- HR-MDS: In 23 evaluable patients (20 had TP53m, 21 had complex karyotype, and seven had therapy-related MDS), the objective response rate (ORR) was
65% .- Nine patients achieved a CR within 16 weeks as the median time to CR. None of the patients with CR progressed as of the data cutoff.
- 16 patients were still undergoing treatment.
- TP53m AML: In 14 evaluable patients (11 of whom had secondary AML) the ORR was
36% . A total of 21 patients will be included in the final pre-conference data cutoff.- Two patients achieved a CR, the median time to CR was 8.7 weeks. Another patient achieved a CR with incomplete hematologic recovery (CRi) and two patients achieved a partial response (PR). None of the responders progressed as of the data cutoff.
- Four responders (one CR, one CRi, two PR) were taken to hematopoietic cell transplantation (HCT)
- Six patients were still undergoing treatment, including one patient in CR.
- Median duration of response and overall survival has not been reached in both HR-MDS and TP53m AML as of the data cutoff date.
Safety: SL-172154 had an acceptable safety profile: Infusion-related reactions (IRRs) were the most common SL-172154 related treatment-emergent adverse events (TEAEs).
- IRR was reported in 18 patients (
46% ); all were Grade 1 and 2 except for two Grade 3 events. Other SL-172154 related TEAEs (>=10% ) were fatigue in five patients (13% ) and hypokalemia in four patients (10% ). - Cytokine release syndrome was reported in two patients with HR-MDS (Grade 2 and Grade 3, respectively).
- 11 patients (
28% ) experienced at least one Grade 3/4 SL-172154 related TEAE, with fatigue, febrile neutropenia, and IRR as the most common (in two patients each). - Two patients had drug discontinuation that were possibly related to SL-172154: one patient had a Grade 4 event of myocardial infarction, and one patient had a Grade 5 event of cardiac arrest. Both patients had a history of significant cardiovascular disease, adverse risk factors and other comorbidities.
About SL-172154
SL-172154 (SIRPα-Fc-CD40L) is an investigational ARC® fusion protein designed to simultaneously inhibit the CD47/SIRPα checkpoint interaction and activate the CD40 costimulatory receptor to bolster an anti-tumor immune response in patients with advanced cancer. Multiple Phase 1 clinical trials are ongoing for patients with platinum-resistant ovarian cancer (NCT04406623, NCT05483933) and patients with AML and HR-MDS (NCT05275439).
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: future presentations of clinical data; clinical development plans and strategies for SL-172154; timing of anticipated clinical data; 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
FAQ
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