GCS 100 IV / Innoviva - LARVOL DELTA

INVOLVEMENT OF ENTERIC GLIAL CELLS AND MAST CELLS IN MICROSCOPIC COLITIS: DISTINCT RESPONSES IN COLLAGENOUS AND LYMPHOCYTIC COLITIS (UEGW 2025) - "On the other hand, EGCS100β+ were increased only in active CC (p<0.0001)... Our findings indicate that EGC and mast cells are involved in CC pathogenesis due to an increased reactivity of EGC and mast cells in the colonic mucosa. CC patients exhibit signs of EGCGFAP+ levels comparable to those observed in UC and IBS-D. Oppositely, LC seems to be independent of neuroinflammation as EGC and mast cells presence was comparable to HC."

Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • GFAP • S100B • S100B

Impact of Baseline Glucocorticoid Use on the Efficacy of Immunoradiotherapy in NSCLC Patients with Brain Metastases (IASLC-WCLC 2024) - "The propensity score matching proved that the group of high GCs use still had significant differences in median iPFS (5.23 months vs 8.93 months, p=0.023), median PFS (4.33 months vs 8.10 months, P=0.046) and median OS (7.47 months vs 14.63 months, P=0.033) comparing with the patients of median GCs use and low GCs use (Figure1). Conclusions : The application of GCs often increased in patients with NSCLC brain metastases receiving immunotherapy combined with intracranial radiotherapy and the baseline high dose GCs use (GCs≥100mg) will reduce the efficacy of the combination therapy and impair the survival outcomes."

Clinical • CNS Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Vascular Neurology

Effect of long-term chronic hyperhomocysteinemia on retinal structure and function in the cystathionine-β-synthase mutant mouse. (PubMed, Exp Eye Res) - "Immunohistochemistry revealed ∼5 RGCs/100 μm retinal length in both Cbs and WT mice at 20 months...We conclude that chronic, moderate Hhcy (at least due to deficiency of Cbs) is not accompanied by retinal structural/functional changes that differ significantly from age-matched WT littermates. Despite considerable evidence that severe Hhcy is toxic to retina, moderate Hhcy appears tolerated by retina suggesting compensatory cellular survival mechanisms."

Journal • Preclinical • Age-related Macular Degeneration • Glaucoma • Macular Degeneration • Metabolic Disorders • Ophthalmology • Retinal Disorders • GFAP

Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma. (PubMed, Cells) - "Caspase-independent mechanisms, mainly based on increased oxidative stress, result from 2-methoxyestradiol, Artesunate, ascorbic acid, Dihydroartemisinin, Evodiamine, b-AP15, VLX1570, Erw-ASNase, and TAK-242. Other agents restore PIs' efficacy through caspase-dependent tools, such as CDDO-Im, NOXA-inhibitors, FTY720, GCS-100, LBH589, a derivative of ellipticine, AT-101, KD5170, SMAC-mimetics, glutaminase-1 (GLS1)-inhibitors, and thenoyltrifluoroacetone. Each of these substances improved the efficacy rates when employed in combination with the most frequently used antimyeloma drugs."

Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology

Galectin 3 Protein Network Analysis By Reverse Protein Arrays Demonstrates Regulation of MCL-1, PKC Delta and CD74 Associated with Poor Survival in Patients with AML (ASH 2017) - "...As reduction of LGALS3 by shRNA or inhibition of LGALS3 using GCS-100 suppresses phosphorylation of ERK, the mechanism how LGALS3 supports MCL-1 in the AML cells may involve ERK...These data suggest that LGALS3 supports AML cell survival via diverse pathways including positive regulation of MCL-1 and PKC delta and support of a CD74 protein network that identifies a new high risk AML population. It is our hope that strategies targeting LGALS3 and CD74 can be developed to help this new at risk population."

Biomarker • Clinical • Acute Myelogenous Leukemia • Biosimilar

Bio-path to uplist shares, TKMR gets a shot in the arm, two to go for NAVB (Nasdaq) - "La Jolla Pharmaceutical Co. ( LJPC ) will be presenting an update on its phase II clinical study of GCS-100 for the treatment of chronic kidney disease at the 26th Annual ROTH Conference on March 10, 2014."

Trial status • Chronic Kidney Disease • Renal Disease

Results from phase 2 study of GCS-100 in chronic kidney disease being presented at American Society of Nephrology Kidney Week (Businesswire) - P2, N=121; NCT01843790; "La Jolla Pharmaceutical Company...today announced that detailed results from its Phase 2 study of GCS-100 in chronic kidney disease (CKD) patients are being presented at a poster session...met its primary efficacy endpoint of a statistically significant improvement in kidney function. Specifically, GCS-100, at a dose of 1.5 mg/m2, led to a statistically significant (p=0.045) improvement in estimated glomerular filtration rate (eGFR)...No statistically significant improvement in eGFR was observed in the 30 mg/m2 dose group."

P2 data • Chronic Kidney Disease • Renal Disease

LaJolla down on clinical trial results (SeekingAlpha) - "...LaJolla Pharmaceuticals...will finish in the red today on a 3x surge in volume as investors head for the exits after the company reported results from a 121-patient Phase 2 clinical trial evaluating the safety and efficacy of GCS-100 in patients with chronic kidney disease."

P2 data • Stock price • Chronic Kidney Disease • Renal Disease

La Jolla Pharmaceutical Company announces final dosing in Phase 2 clinical trial of GCS-100 in chronic kidney disease (La Jolla Press Release) - "La Jolla Pharmaceutical Company...has completed dosing of its Phase 2 clinical trial of GCS-100 for the treatment of chronic kidney disease ('CKD') and has collected the final data for evaluation of the primary endpoint. The primary efficacy endpoint is the change in estimated glomerular filtration rate ('eGFR') from baseline to the average at Day 50 and 57 in each GCS-100 dose group compared to placebo. We look forward to analyzing the data which we expect to release in March."

Anticipated P2 data • Enrollment closed • Chronic Kidney Disease • Renal Disease

La Jolla: Annual Report 2014 (La Jolla) - Anticipated patent expiry in US, Canada and Europe between March 2025 and March 2028; Anticipated expiry of patents on composition and methods of use in US between April 2024 and 2025; Anticipated expiry of provisional patents on methods of use in US and ex-US in March 2035

Anticipated patent expiry • Renal Disease

La Jolla Pharmaceutical Company reports positive, top-line results from phase 2 clinical trial of GCS-100 in chronic kidney disease (La Jolla Press Release) - P2a, N=121; Sponsor: La Jolla Pharmaceutical; NCT01843790; "The trial met its primary efficacy endpoint of a statistically significant improvement in kidney function. Specifically, a dose of 1.5 mg/m2 led to a statistically significant (p=0.045) increase in estimated glomerular filtration rate (eGFR) compared to placebo between baseline and end of treatment. At the 30 mg/m2 dose, there was no statistically significant difference."

P2a data • Chronic Kidney Disease • Renal Disease

Galectin-3 inhibition with GCS-100 improves eGFR in patients with chronic kidney disease (KIDNEY WEEK 2014) - Abstract #TH-PO460; P2, N=117; NCT01843790; Sponsor: La Jolla Pharmaceutical Company; “Short term therapy with the galectin-3 inhibitor, GCS-100 at 1.5 mg/ m2, resulted in small but significant improvement in eGFR. If future, long term studies confirm these findings, GCS-100 could be used as a disease-modifying agent to slow and potentially reverse the renal fibrosis common in CKD.”

P2 data • Chronic Kidney Disease • Renal Disease

La Jolla: Corporate Presentation (La Jolla) - "Encouraging Phase 1 Data"; "GCS-100 @ 30 (mg/m2) Significantly Reduces Galectin-3 Levels"; "Day 7 returns to above baseline level due to mobilization of tissue galectin-3"

P1 data • Renal Disease

La Jolla: Corporate Presentation (La Jolla) - “Additional Confirmatory Data From Extension Study”; “Statistically Significant Change in eGFR at 16 Weeks vs. 30 mg/m2 Group and Placebo”

P2a data • Chronic Kidney Disease • Renal Disease

La Jolla Pharmaceutical company reports results from GCS-100 phase 1 chronic kidney disease clinical trial (PipelineReview) - P1, N=29; Sponsor: La Jolla; NCT01717248; "La Jolla Pharmaceutical...released data...from the Phase 1 (Part A) portion of the Phase 1/2 clinical trial of GCS-100 in patients with...CKD. Based upon the favorable safety profile and encouraging galectin-3 results, the company plans to close this study and initiate a randomized Phase 2a study in early June."

Anticipated trial initiation date • P1 data • Renal Disease

La Jolla: Jefferies Global Healthcare Conference (La Jolla) - "GCS-100 CKD Phase 2 Results"; "Primary endpoint reached for 1.5mg/m² dose"; "eGFR effect correlates with change in galectin-3"; "Multiple secondary endpoints improved and consistent with primary endpoint analysis"; "No Serious Adverse Events (SAE) and no Grade 3/4 events at 1.5mg/m² "; "No adverse effects on hematology lab parameters"

P2 data • Renal Disease

La Jolla Pharmaceutical company receives Notice of Allowance for patent claims covering modified pectin for treatment of chronic inflammation (The Wall Street Journal) - "La Jolla Pharmaceutical...announced that the United States Patent and Trademark Office ('USPTO') has issued a notice of allowance for patent application number 13/888,158 covering methods of treating chronic inflammation using modified pectin....GCS-100...is being studied in a randomized, placebo-controlled Phase 2 clinical study in patients with CDK [Sic]. Data on the primary efficacy endpoint from this study is due to be released in March of this year."

Anticipated P2 data • Patent • Chronic Kidney Disease • Renal Disease

La Jolla: Jefferies Global Healthcare Conference (La Jolla) - Anticipated data from P2 interim extension trial (4003) for chronic kidney disease in 2014; Anticipated presentation of data from P2 trial for chronic kidney disease at American Society of Nephrology (Nov 11-16, 2014 )

Anticipated P2 data • Chronic Kidney Disease • Renal Disease

La Jolla Pharmaceutical company announces data presentation at the American Society of Nephrology Kidney Week (Businesswire) - "La Jolla Pharmaceutical Company...today announced that an abstract of the results for the Company’s Phase 2 clinical trial of GCS-100 in chronic kidney disease (CKD) has been selected by the American Society of Nephrology’s (ASN) Program Committee for poster presentation at the Kidney Week Annual Meeting. Kidney Week will be held November 11-16, 2014 in Philadelphia, Pennsylvania."

Anticipated P2 data • Chronic Kidney Disease • Renal Disease

La Jolla: Corporate Presentation (La Jolla) - “Time Course of Activity Consistent with MoA, Effficacy Endpoint Also Met at End of Study Time Point (5 Weeks post Last Dose)”; “Phase 2a Predefined Analyses, Diabetic Subset Shows Most Improvement”;”Safety Data Summary”; “No Early Terminations at the 1.5 mg/m² dose, 117 of 121 patients enrolled completed the study, Placebo: 40/41 completed; 1 withdrew consent after the first dose, 1.5 mg/m2 41/41 completed, 30 mg/m2: 36/39 completed; 1 withdrew consent before the first dose, 1 withdrew consent after the second dose due to scheduling conflict, 1 subject failed to come back after the 6th dose without explanation”; “No Grade 3 or 4 adverse events at the 1.5 mg/m2 dose, Similar event rate and profile among the groups, more grade 3/4 events in the 30 mg/m2 group”; “No Serious Adverse Events at the 1.5 mg/m2 dose”

P2a data • Chronic Kidney Disease • Renal Disease

Results from phase 2 study of GCS-100 in chronic kidney disease being presented at American Society of Nephrology Kidney Week (Businesswire) - P2, N=93; "An extension study is currently being conducted in which patients from the Phase 2 study were re-randomized...33 patients had previously received placebo in the Phase 2 study before being treated with GCS-100 in the extension study....Consistent with the blinded Phase 2 results, the 1.5 mg/m2 group experienced a significant improvement in eGFR."

P2 data • Chronic Kidney Disease • Renal Disease

North Japan multicenter phase II study of oxaliplatin-containing regimen as adjuvant chemotherapy for stage III colon cancer: final analysis (NORTH/HGCSG1003). (PubMed, Ann Oncol) - No abstract available

Clinical • Journal • P2 data

NORTH/HGCSG1003: North Japan multicenter phase II study of oxaliplatin-containing regimen as adjuvant chemotherapy for stage III colon cancer: Final analysis (ESMO Asia 2019) - "In Japanese patients with resected stage III colon cancer, FOLFOX is a well-tolerable regimen as adjuvant chemotherapy. In this trial, the 3-year DFS rate of primary endpoint was not meet the expectation. However, the 3-year DFS and 5-year OS rate in this trial were similar to several pivotal trials.Legal entity responsible for the study: Non-Political Organization: Hokkaido Gastrointestinal Cancer Study Group."

Clinical • P2 data