![]() Corporate Presentation July 2012 Exhibit 99.1 |
![]() Mission La Jolla Pharmaceutical is Committed to Discovering and Developing Novel Therapies Designed to Modulate Immune Function to Treat Organ Failure and Cancer 2 |
![]() Corporate Highlights 3 Technology • Immune therapy platform targeting, Galectin-3, an emerging key with a demonstrated role in organ failure and cancer via immune regulation • Clear path to proof-of-concept Pipeline • Product candidate: GCS-100 - Leading, clinical stage galectin-3 antagonist May prevent or reverse organ failure by mediating fibrosis via galectin-3 sequestration Binds galectin-3 and reverses T-cell suppression Extensive clinical data with clear single agent activity and favorable safety profile Management and Investors • Experienced and driven Milestones • Near-term, cost-efficient clinical and preclinical milestones to drive value |
![]() Robust Product Pipeline Robust Product Pipeline 4 Products Program/Indication R&D IND Phase 1 Phase 2 Phase 3 GCS-100 Cancer with Renal Insufficiency Cancer Immunotherapy Prevention of Chemotherapy Toxicity End-Stage Renal Disease LJPC-101 Renal Transplantation End-Stage Renal Disease LJPC-201 Heart Failure Hepatic Fibrosis LJPC-301 Cancer – Solid Tumors |
![]() Galectins and Galectin-3 • Galectins are proteins that can bind to sugars proteins to modulate function and communication • Normally present at low concentration, but up-regulated in cancer and organ failure 5 |
![]() GCS-100: The Lead Galectin-3 Antagonist GCS-100: The Lead Galectin-3 Antagonist • GCS-100 is a well-characterized, complex sugar • GCS-100 binds to and neutralizes galectin-3. Binding activity is localized to the galactose containing side-branches • Patented manufacturing process required for biologic activity; unmodified pectin has reduced biologic activity 6 GCS-100 |
![]() Galectin-3 and Organ Failure Galectin-3 and Organ Failure • Galectin-3 knockout mice develop significantly less kidney fibrosis and failure after damage compared to normal mice • Galectin-3 knockout mice do not develop liver fibrosis when exposed to toxin • Galectin-3 serum assay is FDA approved to identify patients at risk for death due to heart failure • Serum galectin-3 levels identify patients with end-stage renal disease who are at highest risk for death 7 4 5 3 1,2 1 The American Journal of Pathology, 2008; Vol. 172, No. 2: 288-298. 2 Transplantation International, 2008; Vol. 21, No. 10: 999-1007. 3 Proceedings of the National Academy of Sciences, 2006; Vol. 103, No. 13: 5060-5065. 4 Annals of Medicine, 2011; 43: 60–68. 5 Galectin-3 and Outcomes in Patients with End-Stage Renal Disease: Data from the German Diabetes and Dialysis Study, presented by Rudolf de Boer, MD, PhD, Associate Professor of Cardiology at the University of Groningen, the Netherlands; American Heart Association Scientific Presentation, November 2011. |
![]() Galectin-3 in ESRD: 2011 AHA Presentation Galectin-3 in ESRD: 2011 AHA Presentation 8 1 Department of Cardiology, University Medical Center Groningen, The Netherlands 2 Department of Medicine, Division of Nephrology, University Hospital Würzburg, Germany Galectin-3 and Cardiovascular Outcomes in Patients with End-Stage Renal Disease Data from the German Diabetes and Dialysis Study Rudolf A. de Boer MD ¹ Christoph Wanner MD ² Katja Blouin MSc ² Christiane Drechsler MD ² |
![]() Galectin-3 in ESRD: Galectin-3 in ESRD: 2011 AHA Presentation Conclusions 2011 AHA Presentation Conclusions • Galectin-3 levels are extremely elevated in patients with ESRD on hemodialysis • High galectin-3 in independently associated with stroke, CV events, all-cause and infectious mortality in dialysis patients 9 |
![]() Galectin-3: Promotes Organ Failure Galectin-3: Promotes Organ Failure via Scar Formation via Scar Formation • Mice genetically altered to lack galectin-3 produce much less scar tissue in the kidney after injury. Normal (wild-type, WT) mice or galectin-3 knockout mice were either left alone (-) or surgically injured by obstructing the outflow of urine from the kidney (UUO). The amount of collagen and procollagen produced is a measure of scar formation. As indicated, galectin- 3 knockout mice produced much less scaring. 10 The American Journal of Pathology, 2008; Vol. 172, No. 2: 288-298. |
![]() Galectin-3 and Cancer Galectin-3 and Cancer • Over-expression of galectin-3 correlates with aggressiveness and relapse in multiple human cancers 1,2 • Galectin-3 expression via transfection increases metastasis in animal models 1,2 • Galectin-3 suppresses anti-tumor T-cell activity 3 • Lung tumorigenesis is reduced in galectin-3-/- vs. wild-type mice 4 • Galectin-3 knockdown reduces proliferation and tumor growth 5 11 1 Reviewed in: Liu, F., et al. 2005. Galectins as Modulators of Tumour Progression. Nature Reviews Cancer. 5:29-41proliferation ane 2 Reviewed in: Takenaka, Y., et al. 2004. Galectin-3 and Metastasis. Glycoconj J. 19:543-549 3 Demotte, N. et al. 2008. Restoring the Association of the T Cell Receptor with CD8 Reverses Anergy in Human Tumor-Infiltrating Lymphocytes. Immunity 28, 414-424 4 Abdel-Aziz, H., et al. 2008. Targeted Disruption of the Galectin-3 Gene Results in Decreased Susceptibility to NNK-Induced Lung Tumorigenesis: An Oligonucleotide Microarray Study. J Cancer Res Clin Oncol. 134:777-788 5 Peng W, et al. 2008. Tumor Associated Galectin-3 Modulates the Function of Tumor Reactive T-cells. Cancer Research 68:7228-7236. |
![]() Galectin-3 Expression Correlates with Galectin-3 Expression Correlates with Reduced Patient Survival Reduced Patient Survival • Survival curve of colorectal cancer patients with positive and negative galectin-3 expression. The prognosis of patients was significantly worse in patients with galectin-3-positive expression (purple line) than in galectin-3- negative patients (blue line) (p=0.0027). 12 Anticancer Research 25: 3117-3122 (2005) Galectin-3 Expression is a Potential Galectin-3 Expression is a Potential Prognostic Marker in Colorectal Cancer Prognostic Marker in Colorectal Cancer |
![]() Galectin-3 Suppresses T-Cell Activation Galectin-3 Suppresses T-Cell Activation 13 Source: Pierre van der Bruggen, Ludwig Institute for Cancer Research Galectin-3 Galectin-3 binding to cell surface glycoproteins blocks Galectin-3 binding to cell surface glycoproteins blocks co-receptor association and cell signal transmission co-receptor association and cell signal transmission |
![]() GCS-100 Reverses Galectin-3 T-Cell Suppression 14 Source: Pierre van der Bruggen, Ludwig Institute for Cancer Research Galectin-3 GCS-100 |
![]() GCS-100 Reverses Galectin-3 T-Cell Suppression • T-cells were collected from 4 ovarian cancer patients and tested for their ability to kill the tumor (T-cell Activity). Untreated cells have little activity. After treating the T-cells with either an antibody to galectin-3 (purple) or with GCS-100 (blue), the T-cells regain their activity and ability to kill the tumor. 15 Source: Dermotte et al. A Galectin-3 Ligand Corrects the Impaired Function of Human CD4 and CD8 Tumor-Infiltrating Lymphocytes and Favors Tumor Rejection in Mice, Cancer Research, Oct 1, 2010 70 (19), pgs. 7476-7488 |
![]() GCS-100 Improves Melanoma GCS-100 Improves Melanoma Cancer Vaccine Cancer Vaccine • Animals treated with GCS-100 in addition to a vaccine against the tumor live much longer than untreated animals or animals treated with vaccination or GCS-100 alone 16 Source: Dermotte et al. A Galectin-3 Ligand Corrects the Impaired Function of Human CD4 and CD8 Tumor-Infiltrating Lymphocytes and Favors Tumor Rejection in Mice, Cancer Research, Oct 1, 2010 70 (19), pgs. 7476-7488 |
![]() GCS-100 Clinical Summary GCS-100 Clinical Summary • >140 patients dosed in 9 Phase 1 and Phase 2 clinical trials Significant clinical activity in multiple cancers, including chronic lymphocytic leukemia (CLL), multiple myeloma (MM), renal cell carcinoma • Pharmacokinetic parameters established Single- and multiple-dose administration of 30-160 mg/m ² – Once daily for 5 consecutive days (21-day cycle) – Effective half-life of 36 hours • Demonstrated single-agent activity • Broad-based synergy in vitro with both chemotherapy and other targeted agents 17 |
![]() GCS-100 Side Effects Consistent with GCS-100 Side Effects Consistent with Immune Modulation Immune Modulation • Doses up to 160 mg/m ² well tolerated in 24-patient solid tumor study No hematological toxicity Only drug-related grade 3 AEs = rash (8%), arthralgia (8%) and myalgia (4%), all consistent with immune effects • Dose-Limiting Toxicity Grade 3 rash • Rash Immune-mediated leucoclastic vasculitis Responds to systemic steroid therapy Not associated with additional organ involvement Develops during, or within 1-2 days after completion of, dosing during a treatment cycle No clinical reports of skin desquamation, necrosis, or ulceration Did not preclude additional treatment cycles with GCS-100 18 |
![]() Phase 2a Single-Agent CLL Study: Design Phase 2a Single-Agent CLL Study: Design • Enrolled 24 patients with one or two prior therapies Median age 67 years old; 15 patients > 67 years, 4 > 80 years Prior therapies include Fludara-, Rituxan- and chlorambucil- containing regimens • Dosing regimen 160 mg/m ² i.v. daily for 5 days on 21-day cycle Regimen from Phase 1 solid tumor study Short (~1 hour) infusion No steroid prophylaxis • Primary objectives Evaluate the short-term effect of GCS-100 on markers of cell death Evaluate decreases in peripheral leukocyte count 19 |
![]() Phase 2a Single-Agent CLL Study: Results Phase 2a Single-Agent CLL Study: Results • GCS-100 was well tolerated Minimal hematologic toxicity 1 patient discontinued due to grade 3 rash No drug-related SAEs • In vivo evidence of caspase activation and apoptotic cell death observed 1 • Preliminary data indicate 6/24 patients (25%) achieved PR and 12/24 (50%) achieved SD, for a 75% disease control rate 2 3 Patients >50% decrease in LN size 1 Patient >50% decrease in WBC with LN shrinkage 2 Patients >50% decrease in WBC 20 1 Cotter F. et al. 2008. 10th International Conference on Malignant Lymphoma 2 Cotter F. et al. 2009. 45th American Society of Clinical Oncology Annual Meeting |
![]() GCS-100 Clinical Summary GCS-100 Clinical Summary • Clinical activity in multiple cancers, including chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and renal cell • Well tolerated and has low toxicity based on >140 patients treated • Broad-based synergy in vitro with both chemotherapy and other targeted agents • Single agent activity observed • Rash, arthralgias, myalgias and increase in neutrophil count consistent with immune effects 21 |
![]() Next Steps: Clinical Trial Rational Next Steps: Clinical Trial Rational • Galectin-3 is is increased in patients with ESRD and the level correlates to overall survival • Galectin-3 knockout mice develop less kidney scar after injury • Patients with ESRD have no existing therapeutic options outside of renal transplantation • ESRD patients have a high mortality rate and biomarkers correlate with survival Albumin Galectin-3 Preservation of urine output 22 |
![]() Next Steps: Clinical Trial Rational Next Steps: Clinical Trial Rational • GCS-100 has shown single-agent activity in cancer • Galectin-3 is is increased in patients with renal failure • Galectin-3 knockout mice develop less kidney scar after injury • Cancer therapies often cause kidney injury and scar formation with reduced renal function • There are no approved therapies for treating renal insufficiency in cancer patients 23 |
![]() Next Steps: Phase 1/2 Study in Cancer Next Steps: Phase 1/2 Study in Cancer Patients with Renal Insufficiency Patients with Renal Insufficiency • Advanced-stage cancer patients (n=18) • GCS-100 alone 160 mg/m 2 weekly • Compare baseline to post-treatment: Serum galectin-3 Renal function Tumor response Immune parameters 24 |
![]() Intellectual Property Position Intellectual Property Position 25 Title Status Coverage Expiration Modified Pectins, Compositions and Methods Related Thereto Issued US 8,128,966 Methods for making biologically active modified or unmodified pectin using tangential flow filtration having a molecular weight between 10 and 250 kD. 2028 Modified Pectins, Compositions and Methods Related Thereto Alllowed US 13/357,325 Biologically active pectin (MW 10-250 kD) from modified or unmodified pectin using tangential flow filtration. 2025 Modified Pectins, Compositions and Methods Related Thereto Pending US 13/400,007 Highly bioactive forms of modified pectin and methods of making modified pectin of high molecular weights and/or lacking low molecular weight materials 2025 Compositions and Uses of Galectin Antagonists Pending US 11/803,150 Methods for reducing the rate of cancer growth by treating with a galectin inhibitor, such as modified pectin, and a topoisomerase inhibitor 2027 |
![]() Corporate Highlights Corporate Highlights Technology • • Pipeline • May prevent or reverse organ failure by mediating fibrosis via galectin-3 sequestration Binds galectin-3 and reverses T-cell suppression Extensive clinical data with clear single agent activity and favorable safety profile Management and Investors • Milestones • 26 Immune therapy platform targeting, Galectin-3, an emerging key with a demonstrated role in organ failure and cancer via immune regulation Clear path to proof-of-concept Product candidate: GCS-100 - Leading, clinical stage galectin-3 antagonist Experienced and driven Near-term, cost-efficient clinical and preclinical milestones to drive value |
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