retaspimycin (IPI-504) / Infinity Pharma - LARVOL DELTA

The Combination of HSP90 Inhibitors and Selumetinib Reinforces the Inhibitory Effects on Plexiform Neurofibromas. (PubMed, Cancers (Basel)) - " We demonstrated that combining selumetinib and SNX-2112 or retaspimycin can achieve better tumor inhibition with synergistic effects. The combination significantly delays the progression of mouse pNFs. The combination of selumetinib and HSP90i has significant synergistic effects, provides therapeutic inhibitor effects, and reduces the selumetinib dosage in combination."

Journal • Neurofibromatosis • Oncology • Pediatrics • Solid Tumor • Transplantation • CDC37 • NF1

Deficiency of HSF4 Increases the Secretion of Small Extracellular Vesicles via Upregulation of Chaperone-Mediated Autophagy. (PubMed, J Cell Biochem) - "Further inhibition experiments showed that blocking HSP70 and HSP90 with apoptozole and retaspimycin, or silencing LAMP2A with siRNA, reduced SEV secretion in HSF4-deficient cells. Collectively, enhanced CMA activity and increased SEV secretion induced by HSF4 deficiency may represent a potential mechanism underlying congenital cataract development."

Journal • Cataract • Ophthalmology • CDC37 • EGFR • HSF4 • HSP90AA1 • TCF4

HSP90 stabilizes visual cycle retinol dehydrogenase 5 in the endoplasmic reticulum by inhibiting its degradation during autophagy. (PubMed, J Biol Chem) - "Deletion of HSP90α or HSP90β by CRISPR-Cas9 or inhibition of HSP90 activity by IPI-504 down-regulates RDH5 protein level, but not its mRNA expression, and this downregulation is restored by autophagic inhibitors (3-MA, CQ and Baf-A1) and siRNA of ATG5 or ATG7, but not by the proteasome inhibitor MG132. RDH5 is a novel client candidate of HSP90. The downregulation of RDH5 may be responsible for the nyctalopia side effect noted in cancer patients receiving HSP90 inhibitor treatment currently in the clinical trial."

Journal • Inherited Retinal Dystrophy • Oncology • Ophthalmology • Retinal Disorders • ATG5 • ATG7 • CDC37 • HSP90AA1 • SQSTM1

HSP90, a common therapeutic target for suppressing skin injury caused by exposure to chemically diverse classes of blistering agents. (PubMed, J Pharmacol Exp Ther) - "Topical treatment with known HSP90 inhibitors, SNX-5422 and IPI-504 post PAO or CEES skin challenge significantly attenuated these chemical-induced skin damage (reduction in overall skin injury and clinical scores). Due to difficulties in determining the exact nature of onsite chemical exposure, a potent drug that can suppress widespread cutaneous damage may find a great utility. Thus, we identified HSP90 as a common molecular regulator of cutaneous inflammation and injury by two distinct warfare vesicants: arsenicals and mustards; and HSP90 inhibitors afford significant protection against skin damage."

Journal • Inflammation • Pain • CXCL1 • HSP90AA1 • NLRP3

The downregulation of HSP90-controlled CRALBP expression is associated with age-related vision attenuation. (PubMed, FASEB J) - "In the zebrafish, inhibition of HSP90 by the intraperitoneal injection of IPI504 reduces the thickness of the retinal outer nuclear layer and Rlbp1b mRNA expression...Taken together, these data indicate that the HSP90-SP1 is a novel regulatory axis of CRALBP transcriptional expression in RPE cells. The age-mediated downregulation of the HSP90-SP1-CRALBP axis is a potential etiology for the night vision reduction in senior people."

Journal • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Targeted Protein Degradation • HSP90AA1

Exploring breast cancer exosomes for novel biomarkers of potential diagnostic and prognostic importance. (PubMed, 3 Biotech) - "Additionally, this in silico analysis found that the anticancer agents and HSP90 inhibitors such as ganetespib, retaspimycin, and tanespimycin would have considerable potential in the treatment of BC. However, these findings need to be further confirmed by laboratory and clinical studies for validating their potential applications. The online version contains supplementary material available at 10.1007/s13205-022-03422-w."

Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • ENO1

HSP90 acts as a senomorphic target in senescent retinal pigmental epithelial cells. (PubMed, Aging (Albany NY)) - "Taken together, these results suggest that HSP90 regulates the SASP and SA-β-Gal activity in senescent RPE cells through associating with distinctive mechanism including NF-κB, HIF1α and lysosomal SA-β-Gal. HSP90 inhibitors (e.g. IPI504) could be a promising senomorphic drug candidate for AMD intervention."

Journal • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • CXCL8 • HIF1A • HSP90AA1 • IL1B • IL6

A Double-blind Study Evaluating IPI-504 and Docetaxel in Patients With Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2; N=226; Completed; Sponsor: Infinity Pharmaceuticals, Inc.; Active, not recruiting -> Completed

Trial completion • Biosimilar • Non Small Cell Lung Cancer • Oncology

Infinity provides company outlook and reports full-year and fourth quarter 2011 financial results (Businesswire) - Anticipated IPI-145 P1 data in healthy subjects and hematological malignancies expected in H2 2012; Anticipated data from the dose-escalation portion of the P1b/2 trial in combination with everolimus in NSCLC patients with a KRAS mutation expected in H2 2012

Anticipated P1 data • Anticipated P1/2 data • Non Small Cell Lung Cancer • Oncology

Stifel Nicolaus Healthcare Conference (Infinity Pharmaceuticals) - Retaspimycin / Infinity Pharma; Anticipated P2 safety evaluation & clinical activity study initiation in NSCLC patients

Anticipated safety study initiation • Non Small Cell Lung Cancer • None

Infinity highlights R&D progress and announces second quarter 2010 financial results (Infinity Pharmaceuticals) -

Infinity intends to commence clinical development of IPI-145 (INK1197) in autoimmune-inflammatory diseases in 2011; Beyond IPI-145, Infinity is collaborating with Intellikine to develop other novel PI3Kdelta-selective, PI3Kgamma-selective & PI3Kdelta/gamma dual-selective compounds from Intellikine's collection

Anticipated clinical development • Pipeline update

Barclays Capital Global Healthcare Conference (Infinity Pharmaceuticals) - retaspimycin (IPI504)/ Infinity Pharma; Expected to present P1 data of IPI-504 in combination with docetaxel & to announce future plans for Hsp90 program in 2011

Anticipated development program

Study Evaluating the Efficacy and Safety of IPI 504 in Patients With Advanced Dedifferentiated Liposarcoma (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: Infinity Pharmaceuticals, Inc.; N=40 -> 0

Enrollment change • Biosimilar • Oncology • Sarcoma

Infinity Pharma: JMP Securities Healthcare Conference (Infinity Pharmaceuticals) - Anticipated composition of matter patent expiry for NSCLC in 2024; Anticipated methods of use patent expiry for NSCLC in 2024

Anticipated patent expiry • Non Small Cell Lung Cancer

Homoharringtonine Combined with the Heat Shock Protein 90 Inhibitor IPI504 in the Treatment of FLT3-ITD Acute Myeloid Leukemia. (PubMed, Transl Oncol) - "Furthermore, co-treatment of HHT and IPI504 led to a synergistic or additive effect on 55.56%(10/18) of acute myeloid leukemia cases tested, including three relapsed/refractory patients. In conclusion, our findings indicate that the combination of HHT and HSP90 inhibitor provides an alternative way for the treatment of FLT3-ITD positive acute myeloid leukemia, especially for relapsed/refractory AML."

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