On April 14, 2023 SystImmune, Inc ("SystImmune"), a clinical-stage biopharmaceutical company specializing in the development of innovative cancer treatments using its established drug development platforms, reported that it will present data from seven preclinical programs in poster presentations at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) meeting, which will be held in Orlando, FL, from April 14th to 19th, 2023 (Press release, SystImmune, APR 14, 2023, View Source [SID1234630116]).

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"Our seven posters presented at AACR (Free AACR Whitepaper) represent the important studies in three therapeutic modalities, which demonstrate the continuous innovation happening at SystImmune. The preclinical validation of the intended functionality and the preclinical safety is encouraging. SystImmune looks forward to the clinical validation of the therapeutic concepts that we build into our biologics platforms." said Dr. Yi Zhu, Ph.D. President & CEO of SystImmune.

"SystImmune is excited to have the opportunity to present our preclinical drug data at AACR (Free AACR Whitepaper). We’re proud of the significant progress made over the last years, and we’re committed to continuing our efforts to deliver high-quality treatments that meet the unmet needs of patients in the field of oncology," said Dr. Martin Olivo, M.D. CMO of SystImmune.

SystImmune will present its findings in several poster sessions at the AACR (Free AACR Whitepaper) meeting, including "Antibody Technologies," "Therapeutic Antibodies, Including Engineered Antibodies," and "Growth Factor Receptors as Therapeutic Targets."

On April 17th, 2023, in the session entitled "Antibody Technologies," the company will present its antibody-drug conjugate preclinical progress:

Abstract Name

Presenter

Presentation Details

BL-B01D1, a novel EGFR×HER3-targeting ADC, demonstrates robust anti-tumor efficacy in preclinical

evaluation

Jahan S. Khalili,

Ph.D.

Poster #2642

BL-M07D1, a novel HER2-targeting ADC, demonstrates potent anti-tumor efficacy in preclinical

pharmacodynamic models

Jahan S. Khalili,

Ph.D.

Poster #2643

BL-M02D1, a novel Trop2-targeting ADC, demonstrates robust anti-tumor efficacy in preclinical

evaluation

Jahan S. Khalili,

Ph.D.

Poster #2644

On April 18th, 2023, in the session entitled "Therapeutic Antibodies, Including Engineered Antibodies," the company will present its Tetra-specific T-cell engager technology:

Abstract Name

Presenter

Presentation Details

Tetra-specific antibody GNC-035: guidance and navigation control (GNC) molecule development for

treatment of ROR1+ malignancies

Jahan S. Khalili,

Ph.D.

Poster #5679

Tetra-specific antibody GNC-039: guidance and navigation control (GNC) molecule development for

treatment of EGFRvIII+ malignancies

Jahan S. Khalili,

Ph.D.

Poster #5680

Tetra-specific antibody GNC-038: guidance and navigation control (GNC) molecule development for

treatment of CD19+ malignancies

Jahan S. Khalili,

Ph.D.

Poster #5681

On April 19th, 2023, in the session entitled "Growth Factor Receptors as Therapeutic Targets," the company will present its advanced Bi-specific EGFR and HER3 antibody:

Abstract Name

Presenter

Presentation Details

Anti-tumor efficacy of SI-B001, a novel EGFR×HER3 bispecific antibody, against EGFR-driven

epithelial tumors alone or in combination with paclitaxel and carboplatin

Jahan S. Khalili,

Ph.D.

Poster #6309

SystImmune Drug Platforms

SEBA
The Specificity Enhanced Bi-specific Antibody (SEBA) is a type of oncology therapeutic that can target functional proteins found on the surface of cancer cells. By blocking the growth signals that cancer cells rely on for survival, SEBA technology holds significant promise for cancer treatment. SEBA molecules are developed to have dependent binding toward one of its targets to increase selectivity and reduce toxicity.

Representative of the SEBA platform is izalontamab (SI-B001) which binds EGFR and HER3 with an EGFR dependency for HER3 engagement. Several novel SEBA molecules targeting growth factor receptors and bi-specific immunomodulators are also in development on this platform.

HIRE
Antibody–Drug Conjugate (ADC) molecules utilize specific antibodies to deliver therapeutic small molecules to cancer cells. These molecules are created in cooperation with Bai-Li Pharmaceutical’s R&D Center of Excellence and enable the development of sophisticated chemistries that give this class of drugs their therapeutic payload. SystImmune’s advanced functional ADC platform class is known as heterogeneity–overcoming, immunogenic death-inducing, resistance–antagonizing, Enhanced–Specificity (HIRE).

Representative of the HIRE platform is BL-B01D1 which binds EGFR and HER3 with an EGFR dependency for HER3 engagement and delivers a DAR-8 Topoisomerase I–inhibiting payload that mediates immunogenic cell death and potent bystander killing. The ADCs BL-M07D1 and BL-M02D1 are also included in this platform class. The HIRE platform is responsible for producing several differentially binding mono-specific, bi–specific and bi-paratopic ADCs at various stages of preclinical development that are advancing from discovery to the pre-IND stage.

GNC
Guidance and navigation control (GNC) molecules are proteins that bind and engage multiple types of cells. In oncology therapeutics, GNCs bind to both cancer cells and immune cells, thereby boosting the immune cell’s ability to eliminate cancer. Each GNC molecule is designed to be multi-functional, with the aim of modulating the immune cell compartments during the killing process and making them more effective in targeting cancer cells.

Representative of the GNC platform is GNC-038, an octavalent, tetra-specific T cell engager designed to target CD19 expressing B cell malignancies. This molecule is the first tetra-specific therapeutic antibody tested in humans and exemplifies the concept of GNCs.

GNC-038 can bind CD3 and CD19 to redirect T cell cytotoxicity toward a specified cancer indication defined by CD19 expression. The molecule can also redirect T cell cytotoxicity toward PDL1 high-expressing cells, representing its potential to convert cancer–cell adaptive resistance into drug sensitivity. GNC-038 can also engage 4-1BB, an activation-induced T–cell costimulatory molecule, in a non-cytolytic fashion, transducing a signal to T cells that are designed to increase functionality throughout serial dosing cycles of therapy.

Alongside GNC-038 are GNC-035 targeting ROR1 and GNC-039 targeting EGFRvIII tumor antigens, respectively.

On April 14, 2023 Harbour BioMed ("HBM", HKEX: 02142), a global biopharmaceutical company committed to the discovery, development, and commercialization of novel antibody therapeutics focusing on immuno-oncology and immunology, reported that the results of its phase Ib clinical trial of porustobart (HBM4003) in combination of toripalimab in patients with advanced high-grade neuroendocrine neoplasms (NENs) (trial code: NCT05167071) had been scheduled for presentation in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 and published in the online proceedings of the AACR (Free AACR Whitepaper) (Press release, Harbour BioMed, APR 14, 2023, View Source [SID1234630115]).

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This is an open label phase Ib clinical study to evaluate the safety, tolerability, PK/PD and preliminary efficacy of porustobart combined with toripalimab in patients with advanced NEN and other solid tumors.

Details and highlights:

Title: A phase Ib dose-expansion study of porustobart, an anti-CTLA-4 heavy chain only monoclonal antibody, in combination with toripalimab in patients with advanced high-grade NENs

Location: Poster Section 47
Poster Board Number: 3
Abstract Presentation Number: CT263

Methods:

Patients (pts) with pretreated advanced high-grade NENs received porustobart at one of the two dose levels (0.3 mg/kg and 0.45 mg/kg) plus toripalimab 240 mg every three weeks (Q3W). The primary endpoint is objective response rate (ORR) per RECIST 1.1 by investigator.

Results:

As of 9 November 2022, 21 pts had been dosed. The median follow-up time was 5.9 months for 0.3 mg/kg dose group and 2.8 months for 0.45 mg/kg dose group, respectively.

Porustobart in combination with toripalimab showed promising anti-tumor activity in advanced high-grade NENs. No significant difference in efficacy was observed between the two dose groups.
The overall ORR and DCR (disease control rate) were 38.9% and 61.1%, respectively, and the 3-month DOR (duration of response) rate was 80%, while the median DOR was not reached.
For patients with NEC (neuroendocrine carcinoma), the ORR and DCR were 38.5% and 69.2%, respectively.
Porustobart in combination with toripalimab showed acceptable safety profile.
Treatment-related adverse events (TRAEs) were reported in 100.0% (21/21) patients, and ≥Grade 3 TRAEs were reported in 33.3% (7/21) patients. The most common (≥20%) TRAEs were hepatic function abnormal, hyperthyroidism, rash, leukopenia, anaemia, pyrexia, neutrophil count decreased, hypothyroidism and thrombocytopenia.
Porustobart in combination with toripalimab showed unique PK/PD signature.
PK data indicated no potential interaction between porustobart and toripalimab.
Porustobart promoted Treg reduction and CD4+ and CD8+ T cell proliferation in periphery attested to its mechanism of action.
Conclusions

Porustobart 0.3 mg/kg or 0.45 mg/kg plus toripalimab 240mg Q3W showed promising anti-tumor activity and an acceptable safety profile in pts with advanced high-grade NENs.

The above results demonstrated robust clinical response rate in difficult-to-treat high-grade NENs that were generally not sensitive to current therapies. The results showed great potential to develop porustobart as a cornerstone therapy in immuno-oncology. The Company is also conducting other clinical studies of combination therapy for other advanced solid tumors, such as hepatocellular carcinoma and melanoma.

About Porustobart

Porustobart is a fully human anti-CTLA-4 monoclonal heavy chain only antibody (HCAb) generated from Harbour Mice. By enhancing antibody-dependent cell cytotoxicity (ADCC) killing activity, porustobart has demonstrated significantly improved depletion specific to high CTLA-4 Treg cells in tumor tissues. The potent anti-tumor efficacy and differentiated pharmacokinetics with durable pharmacodynamic effect presents a favorable product profile. This novel and differentiated mechanism of action has the potential to improve efficacy while significantly reducing the toxicity of the drug in monotherapy and combo-therapy.

On April 14, 2023 Carisma Therapeutics Inc. (Nasdaq: CARM), a clinical stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported three abstracts were accepted for presentation at The American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting held from Friday, April 14 – Wednesday, April 19 in Orlando, FL (Press release, Carisma Therapeutics, APR 14, 2023, View Source [SID1234630114]). The accepted data reinforce the potential of Carisma’s differentiated and proprietary cell therapy platform focused on engineered macrophages as a novel treatment pathway for hard-to-treat cancers and other serious illnesses.

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"The three abstracts being presented at the AACR (Free AACR Whitepaper) Annual Meeting reiterate our commitment to adding robust depth to our engineered macrophage platform," said Michael Klichinsky, PharmD, PhD, Co-Founder and Chief Scientific Officer at Carisma Therapeutics. "As we continue to treat patients with HER2 overexpressing solid tumors in the clinic with our lead program CT-0508, we are excited to present on two of our pre-clinical programs that represent advancements in macrophage-based cell therapy. We believe that our mesothelin program has the potential to bring CAR-M therapy to patients with a variety of mesothelin positive solid tumors, and that our novel engineered microenvironment converter (EM-C) platform has the potential to reverse immunosuppression in the solid tumor and, conversely, reverse inflammation in auto-immune disease."

Accepted for AACR (Free AACR Whitepaper) presentation is, "A phase 1, first-in-human (FIH) study of autologous anti-HER2 chimeric antigen receptor macrophage (CAR-M) in participants (pt) with HER2 overexpressing solid tumors," to be presented by Yara Abdou, MD, of the University of North Carolina Lineberger Comprehensive Cancer Center. This Trials-In-Progress poster provides an overview of the phase 1 FIH study design, objectives, and eligibility criteria, that is evaluating safety, tolerability, cell manufacturing feasibility, trafficking, tumor microenvironment (TME) activation, and preliminary evidence of efficacy of CT-0508 in participants with locally advanced metastatic solid tumors overexpressing HER2.

In the poster presentation, "Macrophages engineered with cytokine switch receptors: Development of a modular platform for rebalancing inflammation in microenvironments," to be presented by Chris Sloas, PhD, Senior Scientist at Carisma, Carisma is presenting a novel immunotherapy platform that harnesses macrophages as "living converters" to locally regulate inflammation for oncology and inflammatory applications. The study demonstrates that this platform offers modularity in controlling the inflammatory status of tissue microenvironments without systemic cytokine antagonism and represents a major advance in macrophage-base cell therapy.

Carisma will also share key findings from recent studies including, "A mesothelin targeting chimeric antigen receptor macrophage (CAR-M) for solid tumor immunotherapy: pre-clinical development of CT-1119," to be presented by Nicholas Anderson, PhD, Principal Scientist at Carisma. The study demonstrated that CT-1119, an autologous human anti-mesothelin chimeric antigen receptor macrophage (CAR-M), can phagocytose, eradicate, and induce an inflammatory response against mesothelin overexpressing solid tumors. These results show that CAR-M is a feasible approach for the treatment of mesothelin overexpressing solid tumors.

The following poster presentations will be published on the AACR (Free AACR Whitepaper) Annual Meeting website and available for registered attendees during the dates/times indicated below:

Tuesday, April 18 at 9:00 am ET: Macrophages engineered with cytokine switch receptors: Development of a modular platform for rebalancing inflammation in microenvironments

Tuesday, April 18 at 9:00 am ET: A mesothelin targeting chimeric antigen receptor macrophage (CAR-M) for solid tumor immunotherapy: pre-clinical development of CT-1119

Tuesday, April 18 at 1:30 pm ET-5:00 pm ET: A phase 1, first-in-human (FIH) study of autologous anti-HER2 chimeric antigen receptor macrophage (CAR-M) in participants (pt) with HER2 overexpressing solid tumors

About CT-0508
CT-0508 is a human epidermal growth factor receptor 2 (HER2) targeted chimeric antigen receptor macrophage (CAR-M). It is being evaluated in a landmark Phase 1 multi-center clinical trial that focuses on patients with recurrent or metastatic HER2-overexpressing solid tumors whose cancers do not have approved HER2-targeted therapies or who do not respond to treatment. Carisma Therapeutics is selecting participants who have tumors of any anatomical origin, but with the commonality of overexpressing the HER2 receptor on the cell surface, which is the target for its CAR-M. The Phase 1 clinical trial is first-of-its-kind, marking the first time that engineered macrophages are being studied in humans. The trial continues to enroll patients at five U.S. sites, including Abramson Cancer Center at The University of Pennsylvania; the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill; City of Hope in Duarte, California; University of Texas MD Anderson Cancer Center in Houston, Texas; and Sarah Cannon Research Institute at Tennessee Oncology – Nashville.

On April 14, 2023 Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of peptide therapeutics to address oncogenic and immune dysregulation that drive cancer, reported the presentation of two late-breaking research posters during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, taking place April 14-19, 2023, in Orlando, Florida (Press release, Sapience Therapeutics, APR 14, 2023, View Source [SID1234630113]).

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"We are thrilled to showcase late-breaking results at this year’s AACR (Free AACR Whitepaper) meeting with data from our ST101 and ST316 programs that address difficult-to-drug cancer targets, C/EBPβ and β-catenin," said Dr. Barry Kappel, founder, CEO and President of Sapience. "These datasets demonstrate the roles of ST101 and ST316 in shifting an immune-suppressive tumor microenvironment to an immune-active state, and support evaluating both agents in coordination with immune-oncology (I/O) therapeutic strategies. In particular, with ST316 set to begin patient dosing in a Phase 1-2 clinical study in mid-2023, we are excited that these datasets further elucidate its unique mechanism of action."

ST101 Abstract Highlights:

ST101 is a first-in-class antagonist of C/EBPβ that has demonstrated clinical proof-of-concept in advanced solid tumors. ST101 is currently being evaluated in the Phase 2 portion of an ongoing Phase 1-2 clinical study in patients with advanced unresectable and metastatic solid tumors (NCT04478279).

As a critical regulator of the immunosuppressive tumor microenvironment, activation of C/EBPβ triggers macrophage polarization toward immunosuppressive M2-type myeloid-derived suppressor cells (MDSCs) and correlates with poor prognosis in several types of human cancer.
ST101 reprograms tumor-associated macrophages (TAMs) from the M2 phenotype toward the immune-promoting M1 phenotype, representing an attractive strategy to enhance antitumor immunity.
In preclinical models, ST101-mediated macrophage polarization to the M1 phenotype enhances the in vivo anti-tumor activity of anti-PD1 checkpoint inhibition.
In patient biopsies, ST101 modulates the tumor immune microenvironment by suppressing genes required for M2 macrophage polarization, culminating in an enhanced CD8 T-cell/Treg ratio.
The data support a novel, macrophage-driven mechanism of action for ST101 and suggest the exploration of ST101 in I/O therapeutic strategies.
Title: "ST101, a peptide antagonist of novel I/O target C/EBPβ, reprograms MDSCs and promotes an immunoactive tumor microenvironment"
Session Title: Late-Breaking Research: Experimental and Molecular Therapeutics 2
Session Date and Time: Tuesday April 18, 2023, 1:30 PM – 5:00 PM
Location: Poster Section 34
Abstract Presentation Number: LB236

ST316 Abstract Highlights:

ST316 is a first-in-class peptide antagonist of the interaction between β-catenin and its co-activator BCL9, a complex that drives oncogenesis in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed. In March of this year, Sapience announced that it received clearance from the U.S. Food and Drug Administration (FDA) to proceed with a Phase 1-2 clinical trial of ST316 for the treatment of solid tumors.

In addition to its direct oncogenic role, dysregulated Wnt/b-catenin signaling also promotes tumorigenesis by suppressing the tumor immune microenvironment (TIME).
Nonclinical data indicate that ST316 exposure to human peripheral blood mononuclear cells shifts M2 macrophages to the M1 phenotype and increases CD8 T-cell activation in macrophage/T-cell mixed cultures.
ST316 enhances the anti-tumor activity of anti-PD-1 checkpoint inhibition in a preclinical triple-negative breast cancer model.
These results support the immuno-therapeutic potential of ST316 to enhance current I/O therapeutic approaches.
Title: "Immunotherapeutic potential of ST316, a peptide antagonist of β-catenin"
Session Title: Late-Breaking Research: Experimental and Molecular Therapeutics 1
Session Date and Time: Sunday April 16, 2023, 1:30 PM – 5:00 PM
Location: Poster Section 35
Abstract Presentation Number: LB016

Abstracts and full session details are available through the AACR (Free AACR Whitepaper) Annual Meeting planner: AACR (Free AACR Whitepaper) Annual Meeting 2023 | Meetings | AACR (Free AACR Whitepaper)

About ST101

ST101, a first-in-class antagonist of C/EBPβ, is currently being evaluated in the Phase 2 portion of an ongoing Phase 1-2 clinical study in patients with advanced unresectable and metastatic solid tumors (NCT04478279). ST101-101 is an open-label, Phase 1-2 dose-finding study designed to determine the safety, tolerability, PK, PD, and proof-of-concept efficacy of ST101 in patients with advanced solid tumors. The study consists of two phases: Phase 1 dose escalation/regimen exploration and Phase 2 dose expansion. In the ongoing Phase 2 dose expansion, Sapience is evaluating patients with GBM, metastatic cutaneous melanoma, castration-resistant prostate cancer and locally advanced or metastatic hormone-receptor positive breast cancer. In the ongoing dose escalation part of the study, ST101 has demonstrated clinical proof-of-concept with a durable RECIST 1.1-confirmed partial response (PR) in a patient with cutaneous melanoma and evidence of long-lasting stable disease in several additional patients. In the ongoing Phase 2 dose expansion part of the study, ST101 has demonstrated clinical proof-of-concept with a mRANO-confirmed partial response in a patient with recurrent GBM and evidence of long-lasting stable disease in several additional patients.

ST101 has been granted Fast Track designation for recurrent GBM and advanced cutaneous melanoma in patients who have disease progression on or after anti-PD-1/anti-PD-L1 therapy, as well as orphan designations from the FDA for Stage IIb-IV melanoma, glioma and AML, and from the European Commission for the treatment of glioma.

About ST316

ST316 is a first-in-class peptide antagonist of the interaction between β-catenin and its co-activator BCL9, a complex that drives oncogene expression in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed. The interaction between β-catenin and BCL9 has previously been considered an ‘undruggable’ target due to the inability of small molecules to inhibit complex formation and antibodies to gain access to the cytoplasm or nucleus to disrupt the interaction. ST316 contains a cell penetration moiety to allow intracellular access and a domain designed to bind the first armadillo repeat domain of β-catenin, a site utilized by BCL9 but no other β-catenin binding partners. ST316 suppresses transcription of oncogenic Wnt target genes regulating proliferation, migration, invasion and the metastatic potential of tumor cells, as well as genes regulating the immunosuppression of the tumor microenvironment.

Sapience has received IND clearance to proceed with a Phase 1-2 clinical study of ST316. The Phase 1 dose-escalation portion of the study is designed as a basket study to enroll patients with tumors likely to harbor abnormalities of the Wnt/β-catenin signaling pathway. Sapience expects to begin dosing patients in the Phase 1 portion in mid-2023 to evaluate the safety, clinical activity, pharmacokinetics and pharmacodynamics of ST316. The Phase 2 dose-expansion portion of the study will enroll patients in four specific tumor types known to harbor abnormalities of the Wnt/β-catenin signaling pathway, including cholangiocarcinoma, colorectal, triple negative breast and ovarian cancers.

On April 14, 2023 Aadi Bioscience, Inc. (NASDAQ: AADI), a commercial-stage biopharmaceutical company focused on developing and commercializing precision therapies for genetically-defined cancers with alterations in mTOR pathway genes, reported the presentation of three posters at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (AACR) (Free AACR Whitepaper), taking place April 14-19, 2023, in Orlando, FL (Press release, Aadi Bioscience, APR 14, 2023, View Source [SID1234630112]).

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The presentations at AACR (Free AACR Whitepaper) 2023 include: a trials-in-progress (TIP) poster for the ongoing PRECISION 1 trial, a registrational directed tumor agnostic study for patients with solid tumors driven by TSC1 or TSC2 alterations; results on the anti-tumor activity of nab-sirolimus in combination with KRAS-G12C inhibitors in xenograft models; and results of a biomarker analysis from the AMPECT trial correlating response to nab-sirolimus with TSC1 and TSC2 inactivating alterations, which includes previously reported response data from AMPECT.

Abstracts and poster presentation details are below:

Title: "Phase 2, multicenter, open-label basket trial of nab-sirolimus for patients with inactivating alterations in TSC1 or TSC2 (PRECISION I)"
Date and Time: Monday, April 17, 2023, 9:00 AM – 12:30 PM
Session Title: Phase II and Phase III Clinical Trials in Progress
Presentation Number: CT057

Abstract highlights:

nab-Sirolimus is a novel albumin-bound mTOR inhibitor (mTORi) approved in the US for adult patients with advanced malignant PEComa.
Eligible patients are ≥12 years old and mTORi-naïve, possess malignant solid tumors with TSC1 or TSC2 inactivating alterations (confirmed by central review of sequencing reports), and have received appropriate standard treatments, as determined by the investigator.
Available data from the AMPECT exploratory analysis and an expanded access program suggest acceptable efficacy and safety of nab-sirolimus, an mTORi with enhanced antitumor activity, in patients with solid tumors harboring inactivating alterations in TSC1 and/or TSC2.
nab-Sirolimus 100 mg/m2 will be given weekly intravenously over 30 minutes on Days 1 and 8 of each 21-day cycle. The primary endpoint is overall response rate per independent radiographic review (IRR) using RECIST v1.1. Other endpoints include duration of response, time to response, progression-free survival by IRR, overall survival, patient-reported quality of life, and safety.
Enrollment began in March 2022. Collaboration with leading next-generation sequencing vendors will expedite the identification of patients with qualifying TSC1 or TSC2 mutations; study access will be facilitated through a "just-in-time" approach to trial location activation.
Based on the prevalence of TSC1 or TSC2 inactivating alterations, the most frequent tumor types expected are bladder, hepatobiliary, endometrial, soft tissue sarcoma, ovarian, and esophagogastric.
Title: "Synergistic anti-tumor activity of nab-sirolimus in combination with KRAS inhibitors (KRASis) sotorasib and adagrasib in KRAS G12C NSCLC and bladder cancer xenografts"
Date and Time: Tuesday, April 18, 2023, 1:30 – 5:00 PM
Session Category: Clinical Research Excluding Trials
Session Title: Combination Therapies for Cancer
Presentation Number: 5484

Abstract highlights:

KRAS is frequently mutated in non-small cell lung cancer (NSCLC) and other tumor types, with KRAS G12C mutation representing ~12% of patients with NSCLC. Sotorasib and adagrasib are approved for the treatment of KRAS­ G12C NSCLC. Mutations in KRAS may lead to mTORC1 activation, and mTOR may contribute to adaptive resistance to KRASis.
This study investigated the antitumor activity of nab-sirolimus in combination with KRASis in KRAS G12C NSCLC and bladder xenograft models.
nab-sirolimus in combination with either sotorasib or adagrasib showed greater tumor growth inhibition, a higher meaningful tumor regression rate and synergistic antitumor activity vs single agent therapy.
A multicenter, single-arm, open-label Phase 1/2 clinical study is planned to determine the recommended Phase 2 dose, safety, tolerability, and efficacy for the combination of adagrasib and nab-sirolimus in patients with KRAS G12C tumors.
Title: "Biomarker analysis from AMPECT correlating response to nab-sirolimus with TSC1 and TSC2 inactivating alterations"
Date and Time: Wednesday, April 19, 2023, 9:00 AM – 12:30 PM
Session Category: Clinical Research Excluding Trials
Session Title: Late-Breaking Research: Clinical Research 3
Presentation Number: LB288

Abstract Highlights:

An exploratory biomarker analysis was performed on samples from patients enrolled in the AMPECT study, a Phase 2, multicenter, open-label trial in advanced malignant PEComa (NCT02494570).
A variety of pathogenic inactivating alterations were observed in TSC1 and TSC2 genes, though TSC2 mutations were most commonly frameshift mutations; no recurring mutations were observed.
A tumor-agnostic study (PRECISION 1: NCT05103358) is now recruiting patients with pathogenic inactivating TSC1 or TSC2 alterations to further examine these biomarker findings.
Full session and meeting details are available through the AACR (Free AACR Whitepaper) Annual Meeting planner: AACR (Free AACR Whitepaper) Annual Meeting 2023 | Meetings | AACR (Free AACR Whitepaper). Each poster will be made available following the date of presentation at AACR (Free AACR Whitepaper), on the investor relations page of the Aadi website at www.aadibio.com