STEMSYNERGY THERAPEUTICS INC. - Florida Company Profile

305-600-1048

FEI@STEMSYNERGY.COM

DENNIS FEI

P1025348

59DT1

Active

Non-Manufacturer

2024-07-17

2029-07-17

2025-07-15

DENNIS FEI

2023-09-22

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Department of Health and Human Services

SMALL MOLECULE MYC DEGRADERS AS NOVEL CANCER THERAPEUTIC AGENTS - PROJECT SUMMARY/ABSTRACT THE MYC FAMILY PROTEINS ARE COMPRISED OF THREE PARALOGS TERMED C-MYC, N-MYC, AND L-MYC. THE MYC PROTEINS PLAY A FUNDAMENTAL ROLE IN CELL PROLIFERATION AND ONCOGENESIS BY REGULATING CELLULAR PROCESSES SUCH AS GENE TRANSCRIPTION, PROTEIN TRANSLATION, CELL CYCLE PROGRESSION, AND CELL DEATH. WHILE N-MYC AND L-MYC DRIVE ONCOGENESIS IN A SMALL NUMBER OF CANCER TYPES, THE REQUIREMENT OF C-MYC IS WIDESPREAD IN A BROAD RANGE OF HUMAN CANCERS. MYC PROTEIN LEVELS ARE HIGHLY REGULATED BY AURORA A: BOTH C-MYC AND N-MYC BIND TO AURORA KINASE A TO “ESCAPE” PROTEASOMAL DEGRADATION. WITH THE SUPPORT OF SBIR PHASE I, WE HAVE SUCCESSFULLY IDENTIFIED NOVEL SMALL MOLECULES THAT 1). DIRECTLY TARGET THE MYC:AURORA A BINDING INTERFACE, 2). POTENTLY DEGRADE BOTH ENDOGENOUS N-MYC AND C-MYC (HENCEFORTH “MYC DEGRADERS”), 3). ARE METABOLICALLY STABLE AND ORALLY BIOAVAILABLE, AND 4). ARE EFFICACIOUS IN INHIBITING THE GROWTH OF TUMORS DEPENDENT ON EITHER N-MYC OR C-MYC. FOR THE SBIR PHASE II PERIOD, WE PLAN TO ADVANCE PRE-CLINICAL DEVELOPMENT OF OUR MYC DEGRADERS WITH AN EMPHASIS ON TREATING C-MYC-DEPENDENT CANCERS. WE PROPOSE TWO SPECIFIC AIMS: SPECIFIC AIM 1: TEST THE EFFICACY OF SSTA-315 ACROSS C-MYC DEPENDENT CANCERS, WHILE IN PARALLEL DEVELOP DERIVATIVE C-MYC DEGRADERS WITH IMPROVED POTENCY AND EFFICACY. SPECIFIC AIM 2: EVALUATE THE SAFETY PROFILE OF SSTA-315 (OR AN ALTERNATIVE LEAD MYC DEGRADER) IN IND-ENABLING GLP TOXICITY STUDIES. SUCCESSFUL COMPLETION OF THE PROPOSED STUDIES WILL COMPLETE IND-ENABLING SAFETY STUDIES FOR OUR LEAD MYC DEGRADER, PREPARING FOR THE IND REGISTRATION WITH THE FDA AS THE IMMEDIATE NEXT STEP. GIVEN THAT MYC PROTEINS ARE DEREGULATED IN MOST HUMAN CANCERS, OUR MYC DEGRADERS HAVE POTENTIAL TO IMPACT THE LIVES OF MILLIONS OF CANCER PATIENTS IN U.S. AND REPRESENT A SIGNIFICANT MARKET OPPORTUNITY.

2000000.00

0.00

0.00

2022-04-05

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Department of Health and Human Services

SMALL MOLECULE N-MYC DEGRADERS AS NOVEL CANCER THERAPEUTIC AGENTS - ABSTRACT THE MYC FAMILY PROTEINS ARE COMPRISED OF THREE PARALOGS TERMED MYC (C-MYC), N-MYC, AND L-MYC. THE MYC PROTEINS PLAY A FUNDAMENTAL ROLE IN CELL PROLIFERATION AND ONCOGENESIS BY REGULATING CELLULAR PROCESSES SUCH AS GENE TRANSCRIPTION, PROTEIN TRANSLATION, CELL CYCLE PROGRESSION, AND CELL DEATH. HIGH LEVELS OF N-MYC PROTEIN (GENE NAME: MYCN) ARE OFTEN FOUND IN TUMORS OF NEUROENDOCRINE ORIGINS, WHERE IT HAS BEEN SHOWN TO DRIVE TUMOR GROWTH. AMPLIFICATION OF THE MYCN LOCUS OCCURS IN APPROXIMATELY 50% OF HIGH-RISK NEUROBLASTOMA, WHICH IS THE MOST COMMON EXTRACRANIAL SOLID MALIGNANCY OF CHILDHOOD. N-MYC PROTEIN LEVELS ARE HIGHLY REGULATED BY AURORA KINASE A: N-MYC BINDS TO AURORA KINASE A TO “ESCAPE” PROTEASOMAL DEGRADATION. THE TOOL SMALL MOLECULE AURORA KINASE A INHIBITOR, CD532, EFFECTIVELY DISSOCIATES N-MYC FROM AURORA KINASE A, RESULTING IN N-MYC PROTEIN DESTABILIZATION AND REGRESSION OF MYCN-AMPLIFIED NEUROBLASTOMAS. ALTHOUGH CD532 IS AN EXCELLENT PROOF-OF- CONCEPT MOLECULE, THIS COMPOUND HAS POOR SOLUBILITY, LIMITED PERMEABILITY, AND POOR METABOLIC STABILITY, MAKING IT A POOR DRUG CANDIDATE. TO OVERCOME THESE LIABILITIES, WE HAVE DEVELOPED DISTINCT, NOVEL SMALL MOLECULES, THAT EFFECTIVELY DISSOCIATE N-MYC FROM AURORA A AND DESTABILIZE N-MYC AND THAT ARE MORE BIOAVAILABLE THAN CD532. FOR SIMPLICITY, THESE COMPOUNDS ARE REFERRED TO AS “N-MYC DEGRADERS”. THE PRIMARY GOAL OF OUR PHASE I PROPOSAL IS TO IMPROVE THE POTENCY, SELECTIVITY, DRUG-LIKE PROPERTIES, AND IN VIVO EFFICACY OF OUR LEAD N-MYC DEGRADER, SSTA-152. WE PROPOSE TWO SPECIFIC AIMS: SPECIFIC AIM 1. INCREASE THE POTENCY AND SELECTIVITY OF SSTA-152. SPECIFIC AIM 2. IMPROVE DRUG-LIKE PROPERTIES AND IN VIVO EFFICACY OF SSTA-152. THE OVERALL GOAL IS TO DEVELOP A CLINICAL N-MYC DEGRADER FOR TREATING N-MYC-DRIVEN CANCERS, WHICH FULFILLS A SIGNIFICANT UNMET NEED IN PATIENTS.

399999.00

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0.00

2021-08-31

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Department of Health and Human Services

DEVELOPMENT OF NOTCH1-SELECTIVE SMALL MOLECULE INHIBITOR FOR THE TREATMENT OF CANCER - ABSTRACT THE INCIDENCE OF ESOPHAGEAL ADENOCARCINOMA (EAC) HAS TRIPLED OVER THE LAST 40 YEARS, BUT FIVE-YEAR OVERALL SURVIVAL IS STILL POOR DUE TO LATE STAGE DIAGNOSIS, METASTASIS, AND HIGH RATES OF RECURRENCE AFTER STANDARD CHEMOTHERAPY. STANDARD-OF-CARE THERAPY (NEOADJUVANT CHEMOTHERAPY, RADIATION, OR BOTH FOLLOWED BY ESOPHAGECTOMY) ACHIEVES ONLY 20% RESPONSE RATES, WHILE 80% OF PATIENTS REMAIN POORLY RESPONSIVE. RECENTLY, WE HAVE SHOWN THAT ABERRANT ACTIVATION OF NOTCH1 SIGNALING CORRELATES WITH POOR THERAPEUTIC RESPONSES AND OUTCOMES IN EAC PATIENTS AND THAT EAC TUMORS ARE DEPENDENT UPON SUSTAINED NOTCH1 ACTIVITY. THE VAST MAJORITY OF R&D EFFORTS TO INHIBIT NOTCH HAVE FOCUSED ON GAMMA SECRETASE INHIBITORS (GSIS), WHICH INHIBIT ALL NOTCH PROTEINS, AND AS A RESULT CAUSE SIGNIFICANT DOSE-LIMITING TOXICITY, LARGELY HAMPERING THEIR CLINICAL UTILITY TO DATE. THUS, THERE IS A SIGNIFICANT UNMET CLINICAL NEED FOR TARGETED THERAPIES AGAINST NOTCH1-DEPENDENT CANCERS SUCH AS EAC. STEMSYNERGY THERAPEUTICS HAS IDENTIFIED A FIRST-IN-CLASS INHIBITOR SERIES THAT BINDS AND INHIBITS THE NOTCH1 TRANSCRIPTIONAL COMPLEX AND LIMITS TRANSCRIPTION OF DOWNSTREAM EFFECTORS OF NOTCH1 SIGNALING. WE HAVE DEMONSTRATED THAT ONLY NOTCH1-DEPENDENT EAC CELL LINES ARE SENSITIVE TO OUR INHIBITORS, WHICH BLOCKED THE GROWTH OF EAC PATIENT-DERIVED XENOGRAFT TUMORS. WE FURTHER IMPROVED PHARMACOKINETICS AND SPECIFICITY TO PRODUCE OUR LEAD CLINICAL CANDIDATE SSTN-302, WHICH IS A HIGHLY POTENT AND SELECTIVE INHIBITOR OF NOTCH1 AND INHIBITS EAC TUMOR GROWTH IN VIVO. FURTHERMORE, SSTN-302 HAS PROMISING ADME PROPERTIES, HIGH ORAL BIOAVAILABILITY, AND MOST IMPORTANTLY - AVOIDS THE DOSE-LIMITING TOXICITY OF GSIS. THIS DIRECT PHASE II PROPOSAL SEEKS TO DETERMINE THE PRECLINICAL SAFETY OF SSTN-302 FOR THE PURPOSES OF ADVANCING A NOVEL NOTCH1 INHIBITOR INTO THE CLINIC.

1976591.00

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0.00

2020-04-17

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Department of Health and Human Services

SMALL MOLECULE INHIBITORS OF NOTCH ACTIVATION COMPLEX KINASE (NACK) AS NOVEL CANCER THERAPEUTIC AGENTS

399999.00

0.00

0.00

2018-08-30

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Department of Health and Human Services

DEVELOPMENT OF AN ORAL WNT INHIBITOR

299999.00

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