- |||||||||| irofulven-1 (LP-100) / Lantern Pharma, Eisai
Trial completion date, Metastases: Irofulven in AR-targeted and Docetaxel-Pretreated mCRPC Patients With Drug Response Predictor (DRP (clinicaltrials.gov) - Jun 14, 2024 P2, N=27, Active, not recruiting, After the selection of the MTD and/or RP2D(s), additional patients will be enrolled at two dose levels, as determined by the Safety Review Committee, until at least 10 patients are treated at each dose to confirm the RP2D(s) prior to initiating enrollment in Phase 1b. Trial completion date: May 2024 --> Aug 2024
- |||||||||| hydroxyureamethylacylfulvene (STAR-001) / Lantern Pharma
Novel acylfulvene LP184 shows single agent and combinatorial efficacy with PARP inhibitors in atypical teratoid rhabdoid tumors (Section 43) - Mar 5, 2024 - Abstract #AACR2024AACR_6538; The dual therapy also demonstrates cytostatic and cytotoxic effects as confirmed by immunofluorescence and western blots (BT37 BrdU = 0.0004, BT37 CC3 = 0.0002, CHLA06 BrdU = 0.0033, CHLA06 CC3 = 0.0117 compared to control). Further studies in vivo are being conducted to test single agent and combination therapies of LP-184 and Rucaparib in ATRT, as our data indicates that the two could provide a compelling treatment option for patients with this poor prognosis brain tumor.
- |||||||||| hydroxyureamethylacylfulvene (STAR-001) / Lantern Pharma
Phase classification, Metastases: Study of LP-184 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - Jan 25, 2024 P1, N=30, Recruiting, Abstract is embargoed at this time. Phase classification: P1a --> P1
- |||||||||| Tavocept (dimesna) / BioNumerik, Lantern Pharma
Journal: A randomized multiplex CRISPRi-Seq approach for the identification of critical combinations of genes. (Pubmed Central) - Dec 18, 2023 lpg2888 and lpg3000 were particularly fascinating for their apparent redundant functions during L. pneumophila human macrophage infection, while lpg3000 alone was essential for L. pneumophila virulence in the amoeban host Acanthamoeba castellanii. Thus, MuRCiS provides a method for rapid genetic examination of even large groups of redundant genes, setting the stage for application of this technology to a variety of biological contexts and organisms.
- |||||||||| hydroxyureamethylacylfulvene (STAR-001) / Lantern Pharma
Phase classification, Metastases: Study of LP-184 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - Nov 7, 2023 P1a, N=30, Recruiting, The first-in-human LP-184 dose escalation Phase 1A trial enrolling solid tumor patients including GBM is planned to launch Q3 2023. Phase classification: P1 --> P1a
- |||||||||| hydroxyureamethylacylfulvene (STAR-001) / Lantern Pharma
Preclinical, Journal, Synthetic lethality: Preclinical efficacy of LP-184, a tumor site activated synthetic lethal therapeutic, in glioblastoma. (Pubmed Central) - Jul 26, 2023 High PTGR1 expression and deleterious DDR mutations are present in approximately one third of PDAC making these patients ideal candidates for clinical trials of LP-184. These results establish LP-184 as a promising chemotherapeutic for GBM with enhanced efficacy in intrinsic or spironolactone-induced TC-NER deficient tumors.
- |||||||||| Tumor sensitization to PARP inhibitors by DNA damaging synthetically lethal acylfulvenes. () - Apr 26, 2023 - Abstract #ASCO2023ASCO_4820;
LP-100 and LP-184 are synthetically lethal resulting from their abilities to cause unresolvable DNA damage where tumor cells express high PTGR1 and are deficient in the HR pathway. LP-184 single agent was superior to PARPi in TNBC and LP-100 combination made an olaparib resistant tumor highly sensitive, thereby facilitating a path to extend the opportunities for both AFs and PARPis and enhance the clinical utilization of PARPi.
- |||||||||| hydroxyureamethylacylfulvene (STAR-001) / Lantern Pharma
LP-184, an acylfulvene class small molecule therapeutic, is synthetically lethal in DNA damage repair deficient cancers (Section 19; Poster Board #11) - Mar 14, 2023 - Abstract #AACR2023AACR_8444; Unlike PARPi, LP-184 has striking activity in both NERD as well as HRD cancers. These strong data have prompted the development of a soon to be launched clinical trial to translate the broad preclinical anticancer activity of LP-184 in solid tumors with HR/NER pathway defects, such as pancreatic, prostate, ovarian and breast cancers.
- |||||||||| irofulven-1 (LP-100) / Lantern Pharma, Eisai
Trial completion date, Metastases: Irofulven in AR-targeted and Docetaxel-Pretreated mCRPC Patients With Drug Response Predictor (DRP (clinicaltrials.gov) - Feb 2, 2023 P2, N=27, Active, not recruiting, These strong data have prompted the development of a soon to be launched clinical trial to translate the broad preclinical anticancer activity of LP-184 in solid tumors with HR/NER pathway defects, such as pancreatic, prostate, ovarian and breast cancers. Trial completion date: Sep 2022 --> May 2023
- |||||||||| irofulven-1 (LP-100) / Lantern Pharma, Eisai
Journal: The mutational impact of Illudin S on human cells. (Pubmed Central) - Dec 26, 2022 Accordingly, ILS treatment led to the rapid recruitment of the Y-family DNA polymerase kappa onto chromatin, supporting its preferential use for ILS lesion bypass. Altogether, our work provides the first global assessment of the genomic impact of ILS, demonstrating the contribution of multiple DNA repair pathways to ILS resistance and mutagenicity.
- |||||||||| LP-284 / Lantern Pharma
Journal: MCL-319 LP-284 - A Highly Potent Small Molecule Targeting Mantle Cell Lymphoma. (Pubmed Central) - Sep 29, 2022 LP-184, a small-molecule DNA-damaging agent, is known to be synthetically lethal in tumors with DNA-repair deficiencies, including tumors with ATM mutations...These MCL cell lines included cell lines resistant to ibrutinib, zanubrutinib, venetoclax, and bortezomib...Because ATM orchestrates the activities of the NER and HR pathways, MCL patients with ATM deficiencies are likely to have better responses to LP-284 treatment. Collectively, these data indicate that LP-284 is a promising preclinical DNA-damaging agent that possesses nanomolar-range anti-tumor activities in multiple and diverse MCL cell lines, with the potential to treat MCL patients who are resistant to other therapies.
- |||||||||| hydroxyureamethylacylfulvene (LP-184) / Lantern Pharma
Preclinical efficacy of LP-184, a tumor site activated synthetically lethal therapeutic, in glioblastoma (West/Central Hall) - Sep 28, 2022 - Abstract #SNO2022SNO_669; Our results indicate that LP-184 is MGMT-agnostic and effective in TMZ-resistant pre-clinical GBM models. Our findings also identify ERCC3-dependent TC-NER activity as a determinant of LP-184 synthetic lethality predicting that LP-184's therapeutic potential will be significantly enhanced in patients with intrinsic or spironolactone-induced NER deficient tumors.
- |||||||||| LP-284 / Lantern Pharma
LP-284 – A Highly Potent Small Molecule Targeting Mantle Cell Lymphoma () - Sep 22, 2022 - Abstract #SOHO2022SOHO_780; LP-184, a small-molecule DNA-damaging agent, is known to be synthetically lethal in tumors with DNA-repair defi ciencies, including tumors with ATM mutations...These MCL cell lines included cell lines resistant to ibrutinib, zanubrutinib, venetoclax, and bortezomib...Because ATM orchestrates the activities of the NER and HR pathways, MCL patients with ATM defi ciencies are likely to have better responses to LP-284 treatment. Collectively, these data indicate that LP-284 is a promising preclinical DNA-damaging agent that possesses nanomolar-range anti-tumor activities in multiple and diverse MCL cell lines, with the potential to treat MCL patients who are resistant to other therapies.
- |||||||||| Tavocept (dimesna) / BioNumerik, Lantern Pharma
Enrollment open, Combination therapy, Metastases: HARMONIC: A Study of LP-300 with Carboplatin and Pemetrexed in Never Smokers with Advanced Lung Adenocarcinoma (clinicaltrials.gov) - Aug 24, 2022 P2, N=90, Recruiting, Collectively, these data indicate that LP-284 is a promising preclinical DNA-damaging agent that possesses nanomolar-range anti-tumor activities in multiple and diverse MCL cell lines, with the potential to treat MCL patients who are resistant to other therapies. Not yet recruiting --> Recruiting
- |||||||||| irofulven-1 (LP-100) / Lantern Pharma, Eisai
Journal: Optimization of the production process for the anticancer lead compound illudin M: process development in stirred tank bioreactors. (Pubmed Central) - Jul 20, 2022 By identifying and controlling key process parameters, the production process for illudin M was transferred from shake flasks into 2 L stirred tank bioreactors reaching a comparable titer (> 900 mg L), which is significantly higher than any previously reported. The insights obtained from 10 L scale pave the way towards further scale-up studies that will enable a sustainable supply of illudin M to support preclinical and clinical development programs.
- |||||||||| irofulven-1 (LP-100) / Lantern Pharma, Eisai
Journal: Optimization of the production process for the anticancer lead compound illudin M: improving titers in shake-flasks. (Pubmed Central) - Jun 11, 2022 The insights obtained from 10 L scale pave the way towards further scale-up studies that will enable a sustainable supply of illudin M to support preclinical and clinical development programs. After strict standardization of seed-preparation and cultivation parameters, a combination of experimental design, empirical trials and additional supply of limiting biosynthetic precursors, led to a highly reproducible process in shake flasks with high titers of illudin M. These findings are the base for further work towards a scalable biotechnological process for a stable illudin M supply.
- |||||||||| hydroxyureamethylacylfulvene (LP-184) / Lantern Pharma
Journal: Dietary Supplementation of a New Probiotic Compound Improves the Growth Performance and Health of Broilers by Altering the Composition of Cecal Microflora. (Pubmed Central) - May 30, 2022 The compound probiotics group was fed a basal diet containing 4.5 × 10 CFU of Lactobacillus LP184 and 2.4 × 10 CFU of Yeast SC167 per gram of basal feed...The positive effects of compound probiotics could be attributed to an improvement in the intestinal morphology and cecal microbial diversity of broilers, effects which are distinct from those of antibiotics. These findings revealed the differences between probiotics and antibiotics in terms of improving broilers' performance and enriched the basic knowledge surrounding the intestinal microbial structure of broilers.
- |||||||||| irofulven-1 (LP-100) / Lantern Pharma, Eisai
Journal: Morning for irofulven, what could be fiNER? (Pubmed Central) - Mar 11, 2022 Cancers with DNA repair dysfunction are vulnerable to DNA damaging agents that that invoke a requirement for the disabled repair mechanism. Genome sequencing, coupled with a detailed understanding of mechanisms of DNA repair, has accelerated the discovery of pathway-selective agents that target DNA repair deficiencies in a tumor tissue-agnostic manner.
- |||||||||| CAP-0121 / Califia Pharma
Preclinical evaluation of CAP-0121 for multidrug resistant cancers (E-Poster Website) - Mar 9, 2022 - Abstract #AACR2022AACR_6943; This response of CAP-0121 in drug resistant xenografts is observed at nontoxic doses. Synergistic action is observed when CAP-0121 is administered in combination with traditional drugs used for treating ovarian cancer, including taxanes, platinum agents, and PARP inhibitors.
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