Navajo Neurohepatopathy

– Positive interim data from Phase 1B clinical trial of SL-172154 in combination with pegylated liposomal doxorubicin (PLD) in platinum-resistant ovarian cancer (PROC) demonstrated an acceptable safety profile and encouraging anti-tumor activity that compares favorably to PLD as a monotherapy; expect to complete enrollment in this expansion cohort in the fourth quarter of 2023 – – Topline data from Phase 1A/B clinical trial of SL-172154 in relapsed/refractory (R/R) acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (HR-MDS) patients as monotherapy and in combination with Azacitidine (AZA) to be presented in a poster presentation at the American Society of Hematology (ASH) Annual Meeting; demonstrated monotherapy response and anti-leukemic activity with an acceptable safety/tolerability profile – – Completed enrollment in frontline expansion cohort in TP53 mutant AML in the third quarter and expect to complete planned enrollment in the frontline HR-MDS cohort in the fourth quarter of 2023; interim data from both cohorts expected in the fourth quarter of 2023 – – Conference call and webcast to be held today, November 9th at 8:00 a.m. ET – AUSTIN, TX and DURHAM, NC, Nov. 09, 2023 (GLOBE NEWSWIRE) -- Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), 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, today reported financial results for the quarter ended September 30, 2023, and provided recent business highlights. “We are encouraged by the interim data for SL-172154 in combination with PLD in a group of PROC patients with advanced disease. These data are early, and require both additional patients and longer follow-up, but provide reason for optimism in this study because an overall response rate of 25-30% with SL-171514 in combination with PLD is distinct from a benchmark response rate of 4% with PLD alone,” said Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. “We look forward to sharing data from our ongoing combination clinical trial with AZA in frontline HR-MDS and TP53 mutant AML in December.” SL-172154 Clinical Update: Phase 1B Clinical Trial of SL-172154 in Combination with PLD in PROC Key Takeaways: Observed three partial responses (one confirmed with 58% reduction in the sum of target lesion diameters and two unconfirmed with 100% and 31% reductions in the sum of the target lesion diameters) out of 11 evaluable patients with PROC for SL-172154 in combination with PLD. The initial data suggest SL-172154 had an acceptable safety profile in combination with PLD. Data overview: As of the data cut-off date of October 31, 2023, 16 adult patients with PROC have been dosed in the ongoing Phase 1B clinical study, of which 11 patients were evaluable for response. Patients had a median of 1.5 prior lines of systemic therapy, 47% had bulky disease measuring >5 cm, 56% were pre-treated with bevacizumab and 88% were resistant to frontline platinum regimen.Preliminary anti-tumor activity: As of the data cut-off date of October 31, 2023, three partial responses (one confirmed, two unconfirmed) had been observed for SL-172154 in combination with PLD. As of November 9, 2023, both patients with unconfirmed partial responses remain on study and have not reached the date of confirmatory response assessment.Response rate benchmark for PLD: The patient population treated in this study to date is similar to the population enrolled in the Pfizer-sponsored JAVELIN Ovarian 200 clinical trial, wherein PLD monotherapy provided an overall response rate of 4%.SL-172154 plus PLD had an acceptable safety profile and is consistent with the safety profile of the individual agents: As of the data cut-off date of October 31, 2023, among the 16 treated patients, the most common SL-172154-related adverse events were infusion related reaction, nausea, fatigue, headache and neutropenia, mostly in Grade 1-2. SL-172154-related adverse events in Grade 3 or 4 were observed in 6 patients: anemia (n=2), aspartate aminotransferase increased (n=2), neutropenia (n=2), alanine aminotransferase increased (n=1), embolism (n=1) and thrombocytopenia (n=1). SL-172154-related IRRs occurred in four patients but were manageable and did not prevent the completion of dosing or lead to discontinuation. There were no Grade 5 adverse events.The Phase 1B combination trial in PROC of SL-172154 in combination with PLD is using the 3 mg/kg dose of SL-172154. Next steps and anticipated milestones: Completion of planned enrollment of the Phase 1B dose-expansion cohort of SL-172154 in combination with PLD in PROC expected in the fourth quarter of 2023. Upcoming Milestones SL-172154 (SIRPα-Fc-CD40L) Topline data from Phase 1A/B dose escalation clinical trial of SL-172154 in R/R AML and HR-MDS to be presented at the 65th ASH Annual Meeting.Initial data from the frontline TP53 mutant AML dose-expansion cohort and frontline HR-MDS dose-expansion cohort combining SL-172154 with AZA expected in the fourth quarter of 2023.Initial data from the ongoing Phase 1B clinical trial of SL-172154 in combination with mirvetuximab soravtansine in PROC expected mid-year 2024.Additional data from the ongoing Phase 1B clinical trial of SL-172154 in combination with PLD in PROC expected mid-year 2024. Third Quarter 2023 Recent Business Highlights and Other Recent Developments ARC Clinical-Stage Pipeline SL-172154 (SIRPα-Fc-CD40L) Enrollment completed in the TP53 mutant AML dose expansion cohort of the Phase 1A/B Clinical Trial of SL-172154 in combination with AZA; enrollment in the HR-MDS cohort expected to complete in the fourth quarter: This trial is evaluating SL-172154 in combination with AZA in both frontline HR-MDS patients and frontline TP53 mutant AML patients. The data from the dose-escalation portion of the clinical trial in primarily R/R patients, which preceded the expansion cohorts in frontline patients, will be presented at the 65th ASH Annual Meeting. The abstract was made available on November 2, 2023. As of the May 25, 2023 data cut-off date used for the ASH abstract, 37 patients with R/R AML or HR-MDS had received SL-172154 as monotherapy or in combination with AZA in the parallel staggered dose-escalation portion of the clinical trial. Patients had a median of two prior lines of therapy. As of the data cut-off date of July 10, 2023 used for efficacy evaluation for the ASH abstract, a monotherapy response in a R/R AML patient and early signals of anti-leukemic activity (in the form of blast count reductions) in patients with R/R AML who received SL-172154 in combination with AZA were observed in a dose-dependent manner. Early signals of activity with SL-172154 in combination with AZA in frontline patients with TP53 mutant HR-MDS were also observed. Out of four evaluable previously untreated TP53 mutant HR-MDS patients, there was one complete response, one marrow complete response, and two stable disease. SL-172154 had an acceptable safety profile as monotherapy and in combination with AZA. Shattuck remains on track to share initial data in the fourth quarter of 2023 from the frontline expansion cohorts in TP53 mutant AML and HR-MDS.Continued Dosing of Patients in Phase 1B Clinical Trial of SL-172154 in Combination with Mirvetuximab Soravtansine in PROC. This trial is evaluating the safety, pharmacokinetics, pharmacodynamic effects, and preliminary anti-tumor activity of SL-172154 administered in combination with mirvetuximab soravtansine in patients with PROC. Mirvetuximab soravtansine is an antibody-drug conjugate targeting folate receptor alpha (FRα), which provides for both direct tumor cell killing as well as enhanced macrophage phagocytosis through binding with Fc gamma receptors and has received accelerated approval for PROC patients whose tumors are shown to be FRα positive, defined as ≥75%, as determined by the VENTANA FOLR1 (FOLR1-2.1) Assay. Preclinical studies have shown that both of these killing mechanisms are complementary to the mechanism of SL-172154 by enhancing the activity of macrophages to phagocytose FRα- expressing ovarian cancer cells, and that SL-172154 may broaden the activity of mirvetuximab soravtansine, particularly in patients with tumors that express lower levels of FRα. Shattuck intends to enroll patients with broader FRα expression, including those with “high” (greater than ≥75%), “medium” (≥50% to <75%), and “low” (≥25% to <50%) expression of FRα, as determined by the VENTANA FOLR1 Assay. Shattuck expects to present initial data from the trial midyear 2024. Upcoming Events Shattuck plans to attend the following investor conference. Details will be announced prior to the event. Evercore ISI HealthCONx Conference (Miami, FL), November 28-30, 2023 65th American Society of Hematology (ASH) Annual Meeting & Exposition, December 9-12, 2023 Poster presentation on topline data from the dose escalation portion of Phase 1A/B clinical trial of SL-172154 as monotherapy and in combination with AZA in primarily R/R AML and HR-MDS patients. The full abstract (#4278) is accessible on the ASH Congress portal and additional details are provided here.Shattuck plans to hold a company-sponsored event following ASH to discuss complete data from the dose-escalation portion of the Phase 1A/B clinical trial of SL-172154 in R/R patients and initial data from the frontline expansion cohorts in HR-MDS and TP53 mutant AML. Details will be announced prior to the event. Conference Call Shattuck Labs will host a conference call at 8:00 a.m. ET today to review third quarter 2023 financial results and provide a general business overview. Investors may participate in the live call via telephone via the toll-free dial-in (888) 440-4368 and using the conference ID: 5023003. To listen to the live webcast, please visit the Investor Relations page of the Shattuck Labs website here. Participants may register for the call here. While not required, interested participants are encouraged to join 10 minutes prior to the start of the event. A replay of the webcast will be available following the conclusion of the live call and will be accessible on the Company’s website. Third-Quarter 2023 Financial Results Cash and Cash Equivalents and Investments: As of September 30, 2023, cash and cash equivalents and investments were $101.1 million, as compared to $185.1 million as of September 30, 2022.Research and Development (R&D) Expenses: R&D expenses were $24.2 million for the quarter ended September 30, 2023, as compared to $18.9 million for the quarter ended September 30, 2022. This increase was primarily driven by an increase in expense associated with an increase in clinical trial costs due to increased clinical trial activity and the manufacture of clinical trial materials to support the ongoing clinical trials of SL-172154, as well as development costs for potential pipeline candidates.General and Administrative (G&A) Expenses: G&A expenses were $5.1 million for the quarter ended September 30, 2023, as compared to $6.6 million for the quarter ended September 30, 2022. This decrease was primarily driven by the recognition of a litigation settlement agreement in the third quarter of 2022.Net Loss: Net loss was $27.5 million for the quarter ended September 30, 2023, or $0.65 per basic and diluted share, as compared to a net loss of $24.6 million for the quarter ended September 30, 2022, or $0.58 per basic and diluted share. 2023 Financial Guidance Shattuck believes its cash and cash equivalents and investments will be sufficient to fund its operations through year-end 2024, beyond results from its Phase 1 clinical trials of SL-172154. This cash runway guidance is based on the Company’s current operational plans and excludes any additional capital that may be received, proceeds from business development transactions, and/or additional costs associated with clinical development activities that may be undertaken. 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 PROC (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, our expectations regarding plans for our preclinical studies, clinical trials and research and development programs, plans for clinical trial design, the anticipated timing of the results from our preclinical studies and clinical trials, the anticipated timing of enrollment in our clinical trials, anticipated timing for preclinical development updates, the clinical benefit, safety and tolerability of SL-172154, and expectations regarding the time period over which our capital resources will be sufficient to fund our anticipated operations. Words such as “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 we believe 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 us 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 our filings with the U.S. Securities and Exchange Commission (the “SEC”)), many of which are beyond our control and subject to change. Actual results could be materially different. Risks and uncertainties include: global macroeconomic conditions and related volatility, expectations regarding the initiation, progress, and expected results of our preclinical studies, clinical trials and research and development programs; expectations regarding the timing, completion and outcome of our 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 our Annual Report on Form 10-K for the year ended December 31, 2022, and subsequent disclosure documents filed with the SEC. We claim the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We expressly disclaim 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 RichardsonVice President of Investor RelationsShattuck Labs, Inc.InvestorRelations@shattucklabs.com SHATTUCK LABS, INC. CONDENSED BALANCE SHEETS(In thousands) September 30, 2023 December 31,2022 (unaudited) Assets Current assets: Cash and cash equivalents$40,632 $47,379 Investments 60,442 113,901 Prepaid expenses and other current assets 11,914 23,304 Total current assets 112,988 184,584 Property and equipment, net 14,796 17,671 Other assets 2,673 3,069 Total assets$130,457 $205,324 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable$2,016 $7,170 Accrued expenses and other current liabilities 12,043 17,795 Total current liabilities 14,059 24,965 Non-current operating lease liabilities 3,615 4,202 Total liabilities 17,674 29,167 Stockholders’ equity: Common stock 5 5 Additional paid-in capital 401,394 396,041 Accumulated other comprehensive loss 7 (877)Accumulated deficit (288,623) (219,012)Total stockholders’ equity 112,783 176,157 Total liabilities and stockholders’ equity$130,457 $205,324 SHATTUCK LABS, INC. CONDENSED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (Unaudited)(In thousands, except share and per share amounts) Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Collaboration revenue$686 $212 $943 $262 Operating expenses: Research and development 24,211 18,862 59,083 61,012 General and administrative 5,073 6,579 14,866 16,303 Expense from operations 29,284 25,441 73,949 77,315 Loss from operations (28,598) (25,229) (73,006) (77,053) Other income 1,057 594 3,395 519 Net loss$(27,541) $(24,635) $(69,611) $(76,534)Unrealized gain (loss) on investments 81 (226) 884 (774)Comprehensive loss$(27,460) $(24,861) $(68,727) $(77,308) Net loss per share – basic and diluted$(0.65) $(0.58) $(1.64) $(1.81)Weighted-average shares outstanding – basic and diluted 42,477,642 42,386,470 42,461,644 42,374,955

– SL-172154 as monotherapy and in combination with azacitidine demonstrates anti-leukemic activity and an acceptable safety and tolerability profile – AUSTIN, Texas and DURHAM, N.C., Nov. 02, 2023 (GLOBE NEWSWIRE) -- Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), 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, today announced the presentation of topline data from the dose escalation portion of its Phase 1 A/B clinical trial of SL-172154 as monotherapy and in combination with azacitidine (AZA) in primarily R/R AML and HR-MDS patients. These data will be featured in a poster presentation at the 65th ASH Annual Meeting, which is being held both virtually and in San Diego, CA from December 9-12, 2023. “Response rates are historically low for heavily pretreated relapsed/refractory AML and HR-MDS patients. We were particularly pleased to observe initial anti-leukemic activity, unique pharmacodynamic activity, and an acceptable safety and tolerability profile for SL-172154 as monotherapy and in combination with azacitidine. We are excited to continue development of our unique bifunctional protein SL-172154, as we seek to improve the lives of patients with hematologic malignancies.” said Dr. Lini Pandite, MBChB, M.B.A., Chief Medical Officer of Shattuck. “The observation of a monotherapy response, dose-dependent increases in serum cytokines, and accumulation of mature myeloid cells in bone marrow support a potential contribution of CD40 stimulation in these heme malignancies. Notably, preliminary data shows anti-leukemic effects detected in previously untreated TP53m-MDS and R/R AML patients. We look forward to sharing additional data from the frontline expansion cohorts later this year. Overall, we are encouraged by the growing body of data that further validates the unique mechanism of action of SL-172154 and its therapeutic potential to address the unmet needs for patients with AML and HR-MDS.” The full abstract (#4278) is accessible on the ASH Congress portal, and additional details are provided below. Title: Safety, Pharmacodynamic, and Anti-Tumor Activity of SL-172154 as Monotherapy and in Combination with Azacitidine (AZA) in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) Patients (pts)Session Title: Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster IIIPresenter: Dr. Naval DaverFormat: Poster PresentationSession Date: Monday, December 11, 2023Time: 6:00 PM - 8:00 PM PT Key Takeaways: SL-172154 monotherapy response was observed in a heavily pretreated patient with R/R AML after just a single cycle of treatment, as well as early efficacy signals for SL-172154 in combination with AZA in previously untreated HR-MDS with TP53 mutant patients. SL-172154 was tolerable at 3mg/kg as a monotherapy and in combination with AZA. Data Overview: As of the abstract data cut-off date of May 25, 2023, 37 adult patients with R/R AML and HR-MDS had received SL-172154 as monotherapy or in combination with AZA in the parallel staggered dose-escalation portion of a Phase 1A/B clinical trial. Patients had a median of two prior lines of therapy.Preliminary signs of anti-leukemic activity: Monotherapy response in a R/R AML patient and early signals of anti-leukemic activity (in the form of blast count reductions) in patients with R/R AML who received SL-172154 in combination with AZA were observed in a dose-dependent manner. Early signals of activity with SL-172154 in combination with AZA in frontline patients with TP53 mutant HR-MDS were observed. SL-172154 monotherapy response (Morphologic Leukemia-Free State) (n=1 at 6 mg/kg) was observed in a heavily pretreated R/R AML patient who subsequently proceeded to allogeneic hematopoietic cell transplantation (allo-HCT).Anti-leukemic activity, in the form of blast count reductions, was observed in R/R AML patients in combination with AZA (n=2 at 1 mg/kg, n=5 at 3 mg/kg) and one patient subsequently proceeded to allo-HCT.Out of four evaluable previously untreated HR-MDS with TP53m patients, there was one confirmed complete response (3 mg/kg), one marrow complete response (1 mg/kg), and two stable diseases (n=1 at 1 mg/kg, n=1 at 6 mg/kg). Two patients subsequently proceeded to allo-HCT. SL-172154 had an acceptable safety profile as monotherapy and in combination with AZA. Infusion-related reactions (IRRs) were the most common SL-172154-related treatment-emergent AEs (TEAEs) and were reported in 13 patients (68%) as monotherapy and 8 patients (44%) in combination with AZA.Other TEAEs observed were increased AST (aspartate aminotransferase) (4; 21%), ALT (alanine aminotransferase) (3; 16%) and nausea (3; 17%) in monotherapy cohorts, and nausea (3; 17%) in combination cohorts. All events of increased AST/ALT were transient.SL-172154 in combination with AZA had an acceptable safety profile with one dose-limiting toxicity event at 6mg/kg of SL-172154. The dose of 3 mg/kg is being evaluated in the dose expansion. CD47 and CD40 target engagement and CD40-dependent pharmacodynamic effects observed at the 3 mg/kg dose. SL-172154 induced elevations in serum IL-12p40, IP-10, IL-8, IL-10, MIP3α, and MCP1 with greater response at 3 mg/kg compared to 1 mg/kg and similar response between 3 mg/kg and 6 mg/kg.In bone marrow, abundant staining of SL-172154 was observed, along with a dose-dependent increase in phagocytic cells within mature myeloid immune cell compartments. Reduction in leukemic blasts was associated with an increase in mature myeloid and phagocytic cell phenotypes. About SL-172154SL-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 PROC (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 StatementsCertain statements in this press release may constitute “forward-looking statements” within the meaning of the federal securities laws, including, but not limited to, the therapeutic potential, efficacy and clinical benefits of SL-172154, the safety, pharmacodynamic and tolerability profile of SL-172154, the anticipated timing of the results from our expansion cohorts, and potential clinical benefit of our product candidates. Words such as “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 we believe 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 us 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 our filings with the U.S. Securities and Exchange Commission (the “SEC”)), many of which are beyond our control and subject to change. Actual results could be materially different. Risks and uncertainties include: global macroeconomic conditions and related volatility, expectations regarding the initiation, progress, and expected results of our preclinical studies, clinical trials and research and development programs; expectations regarding the timing, completion and outcome of our 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 our Annual Report on Form 10-K for the year ended December 31, 2022, and subsequent disclosure documents filed with the SEC. We claim the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We expressly disclaim 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 RichardsonVice President of Investor RelationsShattuck Labs, Inc.InvestorRelations@shattucklabs.com

SL-172154 as monotherapy and in combination with azacitidine demonstrates anti-leukemic activity and an acceptable safety and tolerability pro > AUSTIN, Texas and DURHAM, N.C., Nov. 02, 2023 (GLOBE NEWSWIRE) -- Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), 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, today announced the presentation of topline data from the dose escalation portion of its Phase 1 A/B clinical trial of SL-172154 as monotherapy and in combination with azacitidine (AZA) in primarily R/R AML and HR-MDS patients. These data will be featured in a poster presentation at the 65th ASH Annual Meeting, which is being held both virtually and in San Diego, CA from December 9-12, 2023. “Response rates are historically low for heavily pretreated relapsed/refractory AML and HR-MDS patients. We were particularly pleased to observe initial anti-leukemic activity, unique pharmacodynamic activity, and an acceptable safety and tolerability pro SL-172154 as monotherapy and in combination with azacitidine. We are excited to continue development of our unique bifunctional protein SL-172154, as we seek to improve the lives of patients with hematologic malignancies.” said Dr. Lini Pandite, MBChB, M.B.A., Chief Medical Officer of Shattuck. “The observation of a monotherapy response, dose-dependent increases in serum cytokines, and accumulation of mature myeloid cells in bone marrow support a potential contribution of CD40 stimulation in these heme malignancies. Notably, preliminary data shows anti-leukemic effects detected in previously untreated TP53m-MDS and R/R AML patients. We look forward to sharing additional data from the frontline expansion cohorts later this year. Overall, we are encouraged by the growing body of data that further validates the unique mechanism of action of SL-172154 and its therapeutic potential to address the unmet needs for patients with AML and HR-MDS.” The full abstract (#4278) is accessible on the ASH Congress portal, and additional details are provided below. Title: Safety, Pharmacodynamic, and Anti-Tumor Activity of SL-172154 as Monotherapy and in Combination with Azacitidine (AZA) in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) Patients (pts) Session Title: Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III Presenter: Dr. Naval Daver Format: Poster Presentation Session Date: Monday, December 11, 2023 Time: 6:00 PM - 8:00 PM PT Key Takeaways: SL-172154 monotherapy response was observed in a heavily pretreated patient with R/R AML after just a single cycle of treatment, as well as early efficacy signals for SL-172154 in combination with AZA in previously untreated HR-MDS with TP53 mutant patients. SL-172154 was tolerable at 3mg/kg as a monotherapy and in combination with AZA. Data Overview: As of the abstract data cut-off date of May 25, 2023, 37 adult patients with R/R AML and HR-MDS had received SL-172154 as monotherapy or in combination with AZA in the parallel staggered dose-escalation portion of a Phase 1A/B clinical trial. Patients had a median of two prior lines of therapy. Preliminary signs of anti-leukemic activity: Monotherapy response in a R/R AML patient and early signals of anti-leukemic activity (in the form of blast count reductions) in patients with R/R AML who received SL-172154 in combination with AZA were observed in a dose-dependent manner. Early signals of activity with SL-172154 in combination with AZA in frontline patients with TP53 mutant HR-MDS were observed. SL-172154 monotherapy response (Morphologic Leukemia-Free State) (n=1 at 6 mg/kg) was observed in a heavily pretreated R/R AML patient who subsequently proceeded to allogeneic hematopoietic cell transplantation (allo-HCT). Anti-leukemic activity, in the form of blast count reductions, was observed in R/R AML patients in combination with AZA (n=2 at 1 mg/kg, n=5 at 3 mg/kg) and one patient subsequently proceeded to allo-HCT. Out of four evaluable previously untreated HR-MDS with TP53m patients, there was one confirmed complete response (3 mg/kg), one marrow complete response (1 mg/kg), and two stable diseases (n=1 at 1 mg/kg, n=1 at 6 mg/kg). Two patients subsequently proceeded to allo-HCT. SL-172154 had an acceptable safety pro monotherapy and in combination with AZA. Infusion-related reactions (IRRs) were the most common SL-172154-related treatment-emergent AEs (TEAEs) and were reported in 13 patients (68%) as monotherapy and 8 patients (44%) in combination with AZA. Other TEAEs observed were increased AST (aspartate aminotransferase) (4; 21%), ALT (alanine aminotransferase) (3; 16%) and nausea (3; 17%) in monotherapy cohorts, and nausea (3; 17%) in combination cohorts. All events of increased AST/ALT were transient. SL-172154 in combination with AZA had an acceptable safety pro one dose-limiting toxicity event at 6mg/kg of SL-172154. The dose of 3 mg/kg is being evaluated in the dose expansion. CD47 and CD40 target engagement and CD40-dependent pharmacodynamic effects observed at the 3 mg/kg dose. SL-172154 induced elevations in serum IL-12p40, IP-10, IL-8, IL-10, MIP3α, and MCP1 with greater response at 3 mg/kg compared to 1 mg/kg and similar response between 3 mg/kg and 6 mg/kg. In bone marrow, abundant staining of SL-172154 was observed, along with a dose-dependent increase in phagocytic cells within mature myeloid immune cell compartments. Reduction in leukemic blasts was associated with an increase in mature myeloid and phagocytic cell phenotypes. 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 PROC (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: 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, the therapeutic potential, efficacy and clinical benefits of SL-172154, the safety, pharmacodynamic and tolerability pro SL-172154, the anticipated timing of the results from our expansion cohorts, and potential clinical benefit of our product candidates. Words such as “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 we believe 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 us 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 our filings with the U.S. Securities and Exchange Commission (the “SEC”)), many of which are beyond our control and subject to change. Actual results could be materially different. Risks and uncertainties include: global macroeconomic conditions and related volatility, expectations regarding the initiation, progress, and expected results of our preclinical studies, clinical trials and research and development programs; expectations regarding the timing, completion and outcome of our 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 our Annual Report on Form 10-K for the year ended December 31, 2022, and subsequent disclosure documents filed with the SEC. We claim the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We expressly disclaim 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