On December 13, 2023 Dizal reported that the results of a phase 2 pivotal study of sunvozertinib for the treatment of platinum-pretreated non-small-cell lung cancer (NSCLC) patients with EGFR exon 20 insertion mutations (exon20ins) (WU-KONG6) were published in the peer-reviewed journal The Lancet Respiratory Medicine (IF: 76.2) (Press release, Dizal Pharma, DEC 13, 2023, View Source [SID1234638539]). The publication of these research results further reinforces sunvozertinib’s leading position as a potential best-in-class treatment option, following its selection for an oral presentation at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting.

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Lung cancer is the leading type of cancer with the highest incidence and mortality rates in China. In NSCLC, EGFR represents the most common driver gene mutation, with exon20ins mutations being the most prevalent rare subtype, accounting for approximately 12% of all EGFR mutations. However, due to its unique spatial configuration and high heterogeneity, there has been a persistent lack of safe and effective targeted treatment options for this mutation, leading to limited survival benefits for patients.

Yun Fan, MD, PhD from the Department of Thoracic Oncology at the Cancer Hospital of the University of Chinese Academy of Sciences, and the first author of the paper, emphasized the significant challenge presented by EGFR exon20ins mutations in drug development. Despite various treatment modalities including chemotherapy, traditional EGFR-TKIs, immunotherapy and other targeted therapies, the objective response rate (ORR) in platinum-pretreated NSCLC patients with EGFR exon20ins mutations has not exceeded 50%.

Sunvozertinib is a selective EGFR TKI developed to target a wide spectrum of EGFR mutations. It is the first Chinese innovative drug approved for NSCLC patients with EGFR exon20ins mutations. The National Medical Products Administration (NMPA) granted approval based on the results from the WU-KONG6 study, a single-arm, multicenter phase 2 pivotal study, conducted to evaluate the antitumor efficacy of sunvozertinib in platinum-pretreated advanced stage NSCLC patients with EGFR exon20ins mutations. The study’s primary endpoint, the independent review committee (IRC) -assessed ORR reached 61%, indicating a significant improvement over existing treatment options. With more than 100 different subtypes of EGFR exon20ins reported in NSCLC so far, thus making the treatment with a single agent even more challenging due to the diversified protein structure of different subtypes. However, owing to its unique chemical design and flexible compound, sunvozertinib was able to bind to different subtype proteins, and showed potent anti-tumor activities in cell lines expressing a broad variety of subtypes. More importantly, its activity was translatable to human. The ORRs were higher than 50% among different subtypes enrolled into this study. Additionally, the overall safety is similar to other EGFR TKIs and clinically manageable, which can be well managed in the clinic.

Mengzhao Wang, MD, PhD of the Department of Pulmonary Medicine at the Lung Cancer Center at Peking Union Medical College Hospital, and the first and corresponding author of the paper said, "Sunvozertinib, the first Category-I Innovative Drug approved for the treatment of EGFR exon20ins NSCLC in China, has demonstrated a superior efficacy, safety and convenience profile. It overcomes the existing treatment challenges faced by advanced NSCLC patients with EGFR Exon20ins mutations, offering an effective treatment option for this patient population."

"Sunvozertinib marks the first approved innovative drug from Dizal. We are delighted to see the increasing recognition of sunvozertinib’s potential as the best-in-class therapy for NSCLC patients with EGFR exon20ins mutations," said Xiaolin Zhang, PhD, Chairman and CEO of Dizal, "Dizal is expediting the global clinical research of sunvozertinib and eagerly anticipates collaborating with experts to explore additional treatment possibilities. Our goal is to deliver life-changing treatment options for patients worldwide."

About sunvozertinib (DZD9008)

Sunvozertinib is an irreversible EGFR inhibitor discovered by Dizal scientists targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. In August 2023, sunvozertinib received approval from NMPA for the treatment of advanced NSCLC with EGFR exon20ins mutations after platinum-based chemotherapies. The approval is based on the results of WU-KONG6 study, the pivotal study of sunvozertinib in platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins mutations. The primary endpoint of the study, which was the confirmed overall response rate (cORR) as assessed by the Independent Review Committee (IRC) reached 60.8%. Anti-tumor efficacy was observed across a broad range of EGFR exon20ins subtypes, and in patients with pretreated and stable brain metastasis. In addition, sunvozertinib also demonstrated encouraging anti-tumor activity in NSCLC patients with EGFR sensitizing, T790M and uncommon mutations (such as G719X, L861Q, etc.), as well as HER2 exon20ins mutations.

Sunvozertinib showed a well-tolerated and manageable safety profile in the clinic. The most common drug related TEAEs (treatment emergent adverse event) were Grade 1/2 in nature and clinically manageable.

Two global pivotal studies are ongoing in ≥ 2nd line (WU-KONG1 PART B) and 1st line setting (WU-KONG28), respectively, in NSCLC patients with EGFR exon20ins mutations.

Pre-clinical and clinical results of sunvozertinib were published in peer-reviewed journals Cancer Discovery (IF:39.397) and The Lancet Respiratory Medicine (IF: 76.2).

On December 13, 2023 Imagion Biosystems Limited (ASX: IBX) reported positive results following completion of the IBI10103 phase I clinical trial evaluating the safety and clinical feasibility of MagSense HER2 Imaging Agent (MSH2IA) as an adjunct to MRI for the assessment of axillary lymph node metastasis in patients diagnosed with HER2+ primary breast cancer (Press release, Imagion Biosystems, DEC 13, 2023, View Source [SID1234638538]). The trial met its endpoint of safety and tolerability, and showed that blinded radiologists may be able to distinguish suspicious lymph nodes that are infiltrated with metastatic HER2+ cancer from those involved in a healthy immune response or otherwise normally reactive. Thirteen women definitively diagnosed with HER2+ breast cancer were enrolled and treated with the drug without any safety issues, toxicity or drug-related adverse events reported.

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Imagion Biosystems’ Managing Director & CEO, Dr. Isaac Bright, shares a scientific presentation, providing intricate insights into the Phase I Study conducted with MagSense HER2 Imaging Agent.
Imagion Biosystems’ Managing Director & CEO, Dr. Isaac Bright, shares a scientific presentation, providing intricate insights into the Phase I Study conducted with MagSense HER2 Imaging Agent.
Dr. Isaac Bright, Managing Director and CEO of Imagion, presented the data at the international San Antonio Breast Cancer Symposium last week and said, "Patients with HER2 positive breast cancer need better staging options that are safe, reliable, comprehensive, and less invasive than today’s standard of care – axillary ultrasound and serial biopsy procedures. Too many of these women endure unnecessary interventions that provide incomplete information and impose unnecessary costs on global healthcare systems. We are encouraged by MSH2IA’s potential to increase the accuracy of disease staging, and thus improve treatment decisions."

IBI10103 Phase I Study Results

The IBI10103 clinical trial was closed in October 2023 and evaluated the potential of the world’s first molecularly targeted MRI contrast agent, MSH2IA (MagSense HER2 Imaging Agent), to enhance clinicians’ ability to non-invasively and more accurately determine the stage of HER2+ breast cancer. This trial, which was a multi-center open-label study, demonstrated the drug is safe and well-tolerated.

An international panel of blinded radiologists assessed pre-dose versus post-dose MRI scans of treated patients. 5 patients’ scans were not interpretable due to image artifacts or tumor invasion that precluded lymphatic drainage of MSH2IA to axillary lymph nodes. In a comprehensive assessment of the other 8 patients’ scans, the radiologists recognized MSH2IA uptake in both normal and malignant lymph nodes. Normal lymph nodes were recognized by a uniformly dark contrast distributed throughout the entire node. Tumor-metastasized lymph nodes were observed to have heterogeneous scattered darkening. Importantly, MRI assessment of post-MSH2IA imaging achieved parity or outperformed standard-of-care axillary ultrasound imaging in all 8 of these patients. Molecular MRI with MSH2IA achieved nearly perfect patient-level concordance, as 7 of these 8 patients identified with tumor-metastasized lymph nodes post-MSH2IA MRI imaging were confirmed by post-surgical pathology analysis to have metastatic disease. The Company continues to work towards its Investigational New Drug application for submission to the US FDA, which was initially planned for Q1:2024, but now likely to be delayed as Imagion works to ensure sufficient resources are in place to pursue clinical development of the MagSense imaging technology. As the global first-mover enabling molecular MRI, these results are very promising for Imagion and for improved precision oncology care. The Company is encouraged by the feedback IBI10103 results are attracting from prospective partners.

San Antonio Breast Cancer Symposium Poster

Dr. Bright announced these findings last week in a premiere Spotlight poster presentation titled, ‘Noninvasive Detection of Lymph Node Involvement in Subjects with Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Cancer using the MagSense HER2 Test Reagent – A First-In-Human Phase I Study’ at the international San Antonio Breast Cancer Conference.

You can download a copy of the poster HERE >> View Source

About HER2+ Breast Cancer

More than 2 million women worldwide are diagnosed with breast cancer annually, and approximately 20% of them are diagnosed with HER2+ breast cancer. Accurate disease staging is crucial, as treatment strategies vary based on primary tumor characteristics, lymph node status, and more distant metastatic disease. The current clinical standard of care for breast cancer staging relies on clinical assessment and diagnostic imaging. Axillary ultrasound for staging breast cancer is highly subjective and operator-dependent – as many as 50% of breast cancer patients may have their disease inaccurately staged. Inaccuracies at the outset of disease management leave a number of patients inadequately treated and subject others to wasteful and potentially harmful treatments and interventions. Molecular MRI with MSH2IA may emerge as the new standard of care for accurately staging the disease in patients diagnosed with HER2+ breast cancer.

About MagSense HER2 Imaging Agent

The MagSense HER2 Imaging Agent features a superparamagnetic iron oxide nanoparticle core synthesized at Imagion’s GMP-compliant facility in San Diego, CA. It is coated with biocompatible polymers and functionalized with the monoclonal antibody trastuzumab or Herceptin. MSH2IA is designed to be a single dose injected near the primary tumor and has been proven to drain through lymphatics, specifically targeting and binding to HER2+ breast cancer cells.

On December 13, 2023 Inhibitor Therapeutics, Inc. ("Inhibitor") (OTCQB: INTI) has entered into an exclusive, worldwide licensing agreement (the "License") with Johns Hopkins University (JHU) for their U.S Patent 8,980,930 (Canada Patent 2,572,223) "New Angiogenesis Inhibitors" (Press release, Inhibitor Therapeutics, DEC 13, 2023, View Source [SID1234638537]). Angiogenesis Inhibitors, as described by the National Cancer Institute, are unique cancer fighting agents as they block the growth of blood vessels that support tumor growth rather than blocking the growth of the tumor cells themselves. Inventors affiliated with JHU developed this patent, listing Itraconazole as an Active Pharmaceutical Ingredient (API) that has anti-angiogenic properties.

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The License notes field of use is for use in Prostate Cancer, Basal Cell Carcinoma including Basal Cell Carcinoma Nevus Syndrome (an orphan oncology disease), and Lung Cancer, all of which emphasize a significant unmet need. Inhibitor believes the License is a mutually beneficial agreement, yielding a modest annual royalty rate with milestone payments typical to such a license.

Within the literature Head et al1 explains the long-term recognition that angiogenesis is a requirement for tumor growth and metastasis and that growing tumors can promote angiogenesis by secreting proangiogenic factors such as VEGF, basic FGF, EGF and others. These proangiogenic factors stimulate the proliferation, migration, and differentiation of the endothelial cells that make up the inner layer of all blood vessels, causing them to form new vessels that grow towards the source of these factors, this process termed "tumor angiogenesis". It is identified that the major target of itraconazole in endothelial cells is VDAC1. VDAC1 knockdown profoundly inhibits mTOR activity and cell proliferation in HUVEC revealing a previously unknown connection. Inhibition of VDAC1 by itraconazole leads to an increase in cellular AMP:ATP ratio and activation of the AMP-activated protein kinase (AMPK), an upstream regulator of mTOR. VDAC1-knockout cells are resistant to AMPK activation and mTOR inhibition by itraconazole, demonstrating that VDAC1 is the mediator of this activity. In their testing it was found that by using a phenotypical approach starting with the effect of itraconazole the G1-S cell cycle transition of the endothelial cells, itraconazole specifically inhibited the mTOR signaling pathway by downregulating the kinase activity of mTORC1.

Chow Et Al2 completed a study utilizing RNA sequencing to decipher the biological pathway propelling BCC growth. From the assay results, it was observed that BCCs exhibited a considerable amplification in the expression of the mTOR pathway. This pathway plays an essential role in regulating angiogenesis, the growth of new blood vessels from pre-existing ones. Thus, this indicates that it is the heightened activity of the mTOR pathway, and the consequent enhancement of angiogenesis, that stimulates the growth.

Data from Inhibitor’s completed Phase 2b SCORING Trial complements the literature with reference to the Lesion Response of the study which shows that across the 477 target lesions the investigators reported reductions of any size from baseline for 399 (83.65%) lesions, 64 (13.42%) had no change and 14 increased in size. A pre-determined reduction of 30% or greater was seen in 275 of the 477 (57.7%) target lesions, including 130 lesions which resolved completely (27.3%). A total of 13 new ‘surgically eligible’ lesions across 8 of the 38 patients developed over the duration of the study.

For more information about Inhibitor and our mission please visit us on our website (www.inhibitortx.com) and for any further or specific queries you may have please visit our contact us page, submit your details/query, and a representative will be happy to get in touch.

On December 13, 2023 Verastem Oncology (Nasdaq: VSTM) (the "Company"), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported that it has initiated its international confirmatory Phase 3 RAMP 301 trial (GOG-3097; ENGOT-ov81/NCRI), evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent low-grade serous ovarian cancer (LGSOC) (Press release, Verastem, DEC 13, 2023, View Source [SID1234638536]).

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"Patients and treating physicians have advocated for more research and development in support of LGSOC. At Verastem Oncology, we are moving with urgency to offer a Phase 3 study specifically directed at this disease in an effort to address this need," said Dan Paterson, President and Chief Executive Officer, Verastem Oncology. "Based on our Breakthrough Therapy Designation, the initiation and expected progress of this trial, along with the FRAME study data and mature RAMP 201 data, we plan to file for Accelerated Approval in the first half of next year, moving us a significant step closer to addressing the treatment needs of patients living with LGSOC."

RAMP 301 is the confirmatory study required by the U.S. Food and Drug Administration (FDA) for the combination of avutometinib and defactinib to potentially receive full approval for the treatment of recurrent LGSOC. The Company intends to submit an Accelerated Approval New Drug Application (NDA) for the combination of avutometinib and defactinib based on mature data from the Company’s Phase 2 registration-directed RAMP 201 trial, together with the results of the investigator-initiated FRAME trial. The company recently reported results of Part A of the RAMP 201 trial, including confirmed objective response rates (ORR) by blinded independent central review of 45% with a response rate and safety profile consistent with previous studies.​

"LGSOC has a unique molecular, histologic, and clinical profile that differs dramatically from the most common type of ovarian cancer. Response rates to standard of care treatments are disappointing, and there are still no FDA approved treatments specifically for LGSOC," said Rachel Grisham, M.D., Section Head, Ovarian Cancer and Director, Gynecologic Medical Oncology at Memorial Sloan Kettering Cancer Center in Westchester, NY and RAMP 301 global lead investigator. "The combination of avutometinib and defactinib continues to show promise in recurrent LGSOC, and I am looking forward to leading this confirmatory trial with the goal of establishing a new standard of care for people with this rare form of ovarian cancer."

According to Professor Susana Banerjee, MBBS, MA, PhD, FRCP, Consultant Medical Oncologist and Research Lead for the Gynaecology Unit at The Royal Marsden NHS Foundation Trust, Team Leader in Women’s Cancers at The Institute of Cancer Research, London, and lead European investigator of the RAMP 301 trial, "Based on my experience treating women with LGSOC, it’s clear that we need better therapeutic options. I am pleased this Phase 3 trial, following the initial positive results from the Phase 2 RAMP 201 trial, is enrolling patients to potentially address the significant limitations we have seen with other available therapies."

RAMP 301 (GOG-3097; ENGOT-ov81/NCRI) is an international collaboration between The GOG Foundation, Inc. (GOG) and the European Network of Gynaecological Oncological Trial groups (ENGOT) sponsored by Verastem Oncology. The trial is expected to enroll 270 patients who will be randomized to either the combination of avutometinib and defactinib or investigator’s choice chemotherapy (pegylated liposomal doxorubicin, paclitaxel, topotecan) or hormone therapy (letrozole, anastrozole). The primary endpoint is progression free survival (PFS) by Blinded Independent Central Review. Secondary endpoints include ORR, duration of response​, disease control rate, safety and tolerability, patient reported outcomes, and overall survival. RAMP 301 is a global trial with enrollment open in the U.S. and planned enrollment in Canada, the United Kingdom, Europe, Australia, and Korea.

Dr. Grisham and Dr. Banerjee are paid consultants for Verastem Oncology.

About the Avutometinib and Defactinib Combination

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition. In contrast to currently available MEK inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The U.S. Food and Drug Administration granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK clamp avutometinib, with defactinib, its FAK inhibitor, for the treatment of all patients with recurrent LGSOC regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.

Verastem Oncology is currently conducting clinical trials with its RAF/MEK clamp avutometinib in RAS pathway-driven tumors as part of its (Raf And Mek Program). RAMP 301 is a Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent LGSOC. RAMP 201 is a Phase 2 registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC and has completed enrollment in the dose optimization and expansion phases and is enrolling for low-dose evaluation. Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) and KRAZATI (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively. Supported by the "Therapeutic Accelerator Award" Verastem Oncology received from PanCAN, the Company is conducting RAMP 205, a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer.

About Low-Grade Serous Ovarian Cancer (LGSOC)

LGSOC is a highly recurrent, chemotherapy-resistant cancer, associated with slow tumor growth and high mortality rate. Approximately 6,000 women in the U.S. and 80,000 worldwide are living with this disease. Mutations in the KRAS gene are present in 35-57% cases of LGSOC. LGSOC is most often diagnosed in women between the ages of 45-55 years and has a median survival of approximately ten years. The majority of patients experience severe pain and complications as the disease progresses. Chemotherapy is the standard of care for this disease, with limited treatment options currently available.

On December 13, 2023 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, reported initial topline dose-expansion data from its ongoing Phase 1A/B clinical trial of SL-172154 in combination with AZA in frontline HR-MDS and TP53m AML patients (Press release, Shattuck Labs, DEC 13, 2023, View Source [SID1234638533]). Initial data from the dose-expansion cohorts build on the complete dose-escalation data featured in a poster presentation on December 11, 2023 at the 65th ASH (Free ASH Whitepaper) Annual Meeting.

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"Both the frontline HR-MDS and TP53m AML expansion cohorts enrolled quickly after completion of the dose escalation study in the middle of this year, and we are pleased to share initial efficacy data, which begin to demonstrate the activity of SL-172154 beyond what is expected of AZA alone. In dose escalation, we saw a monotherapy response to SL-172154 in a heavily pre-treated relapsed/refractory (R/R) TP53m AML patient that allowed the patient to receive a stem cell transplant. That patient remains disease free." said Dr. Lini Pandite, MBChB, M.B.A., Chief Medical Officer of Shattuck. "In frontline, the rate of complete responses in both the HR-MDS and TP53m AML cohorts is already encouraging, and when coupled with the observation of peripheral blood count recovery in most patients that have not yet achieved a complete response, and the fact that many of these patients are very early in their course of treatment and have not yet reached the median time at which a complete response is expected for azacitidine, suggests that the complete response rate may continue to improve in the coming months. As a result, we have amended both studies to increase the sample size and look forward to providing another update by mid-year 2024."

Phase 1B Trial of SL-172154 in Frontline TP53m AML and HR-MDS

Key takeaways: Early efficacy observed for SL-172154 in combination with AZA in previously untreated HR-MDS and TP53m AML:

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HR-MDS: In 14 evaluable patients with previously untreated HR-MDS (13 of whom had TP53m or deletion), five patients achieved a CR. Four patients achieved a mCR (3 with hematologic improvement in at least one lineage), and two patients achieved stable disease (both with hematologic improvement in at least one lineage).

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TP53m AML: In 11 evaluable patients with previously untreated TP53m AML, two patients achieved a CR. Another patient achieved a CRi and was taken to allogeneic hematopoietic cell transplantation (allo-HCT). Seven additional subjects with stable disease had blast reductions, five of which had recovery of platelets or neutrophils and remain on study and their response may improve. One subject died during the first cycle.

•
Safety: Preliminary data suggest that SL-172154 has an acceptable safety and tolerability profile in combination with azacitidine.

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Data Overview: As of the data cut-off date of December 1, 2023, 14 frontline patients enrolled in the TP53m AML cohort, and 22 frontline patients enrolled in the HR-MDS cohort. Initial enrollment was completed in the fourth quarter of 2023 and Shattuck has elected to expand the cohorts with additional data expected mid-year 2024.

•
Preliminary signs of anti-tumor activity: Early signals of activity, in the form of rapid blast count reductions, were observed in 100% of frontline TP53m AML patients treated with SL-172154 in combination with AZA who received an on-treatment bone marrow biopsy. Most patients in the HR-MDS cohort showed blast count reductions with hematologic improvement early in the treatment course.

•
SL-172154 had an acceptable safety and tolerability profile: Infusion-related reactions (IRRs) were the most common SL-172154 related treatment-emergent adverse events (TEAEs).

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In the TP53m AML and HR-MDS cohorts, IRRs were reported in seven patients (50%) and seven patients (32%) respectively.

•
Grade 3 or 4 AEs related to SL-172154 were reported in two patients (14%) in TP53m AML and four patient (18%) in HR-MDS, including IRR (2), increased AST (1), increased ALT (1), fatigue (1), hypoxia (1), pneumonia (1), chondrocalcinosis (1), and febrile neutropenia (1). There were no reports of destructive anemia.

•
In the TP35m AML expansion cohort, there was one Grade 5 AE of cardiac arrest reported in one patient with history of coronary artery disease, recent arrhythmia, and hypokalemia in the setting of amiodarone use. In the HR-MDS cohort, there were no Grade 5 AEs related to SL-172154 reported.

Phase 1A Trial of SL-172154 in R/R AML and HR-MDS and Frontline TP53m HR-MDS

A copy of the ASH (Free ASH Whitepaper) presentation, titled "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)," is accessible under posters in the "Our Science" section of Shattuck’s website.

Key takeaways: Anti-tumor responses were observed as monotherapy and in combination with AZA. SL-172154 alone and in combination with AZA had an acceptable safety profile, consistent with the safety profile of the individual agents (see SL-172154 safety above). No destructive anemia was observed.

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Data Overview: As of the data cut-off date of September 15, 2023, 32 adult patients with R/R AML and HR-MDS 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. An additional five subjects with frontline TP53m HR-MDS received SL-172154 with AZA.

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Preliminary signs of anti-tumor 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.

•
SL-172154 monotherapy activity (Morphologic Leukemia-Free State) was observed in a heavily pretreated R/R AML patient and subsequently proceeded to allo-HCT.

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Patient achieved MLFS (blast reduction from 19% to <5%) after one cycle of SL-172154.

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Anti-tumor activity was also observed in combination with AZA in previously untreated TP53m HR-MDS patients. Out of four evaluable previously untreated TP53m HR-MDS patients, there was one CR and one mCR. One patient with mCR and one patient with SD proceeded to allo-HCT. The patient in a CR remains in a CR long term.

Conference Call at 8:00 a.m. ET Today

Shattuck will host a conference call today at 8:00 a.m. ET featuring key opinion leader Dr. Naval Daver, MD, (Professor, Director Leukemia Research Alliance Program, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX) to present the initial data from the frontline expansion cohorts in HR-MDS and TP53m AML. Additionally, a review of data from the poster presentation featured at the 65th ASH (Free ASH Whitepaper) Annual Meeting will be discussed. 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.

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).