A brief overview of ROSALIND - a smart data platform designed to provide better personalized treatment options to cancer patients based on their genetic profile.
Pathway analysis for personalized oncologyAnton Yuryev
1) The document discusses using pathway analysis and pathway activity signatures to enable more personalized cancer treatment. It outlines calculating major expression regulators from patient omics data and mapping them to cancer pathways to determine activated pathways.
2) Calculating pathway activity signatures which are short allows better patient classification compared to single targets. Pathway activity also allows selection of drugs that inhibit the active pathway.
3) An example shows a patient's tumor signaling pathway was identified and treatment with drugs targeting the pathway led to no cancer metastasis. The approach aims to continue validating with more medical collaborators.
Construction of cancer pathways for personalized medicineAnton Yuryev
This document discusses constructing cancer pathways for personalized medicine using sub-network enrichment analysis (SNEA). SNEA calculates the transcriptional activity of upstream regulators using differentially expressed genes and regulatory knowledgebases. This identifies key expression regulators in specific cancer patients. Mapping these regulators onto known pathways builds personalized cancer pathways for each patient. Analyzing pathways from multiple patients provides insights into common cancer biology and identifies potential drug targets in a personalized manner.
Informa - Demonstrating Your PARP Inhibitor's ValueDan Ngo
The document discusses making a business case for a PARP inhibitor drug in the ovarian cancer market. It provides information from various data sources on competitor drugs and clinical trials, the size of the ovarian cancer market, sales forecasts for Lynparza and other PARP inhibitors, and deal values that phase 1 oncology drugs and PARP inhibitors have achieved when licensed.
There are several genomic tests that can help predict the risk of recurrence of early-stage breast cancer and determine the benefits of chemotherapy, including Oncotype DX, MammaPrint, Mammostrat, and Prosigna. Oncotype DX analyzes the activity of 21 genes and assigns a Recurrence Score between 0-100, with scores below 18 indicating a low risk cancer unlikely to benefit from chemotherapy. MammaPrint analyzes 70 genes to determine a low or high risk classification. Mammostrat measures levels of 5 genes to calculate a risk index score. Prosigna analyzes 58 genes to estimate the risk of distant recurrence within 10 years as low, intermediate, or high risk. Of the tests, Oncotype
In a narrow sense of cancer biomarker, it is limited to proteins the most used to challenge in the clinical applications, especially in the CAR-T therapy. Specifically, a cancer biomarker of the CAR-T provides the most prominent signal of cancer cells for distinguishing from normal cells and the most effective CAR T target for immune recognition and destruction. https://www.creative-biolabs.com/car-t/biomarker-identification-selection.htm
Speaker: Lisette Stork-Sloots, Sr Program Director at Agendia, discusses how their technology, MammaPrint was commercialized.
Part of Dx2010, a workshop at MaRS focused on best practices and regulatory considerations for developing gene-based diagnostic and prognostic tests.
A brief overview of ROSALIND - a smart data platform designed to provide better personalized treatment options to cancer patients based on their genetic profile.
Pathway analysis for personalized oncologyAnton Yuryev
1) The document discusses using pathway analysis and pathway activity signatures to enable more personalized cancer treatment. It outlines calculating major expression regulators from patient omics data and mapping them to cancer pathways to determine activated pathways.
2) Calculating pathway activity signatures which are short allows better patient classification compared to single targets. Pathway activity also allows selection of drugs that inhibit the active pathway.
3) An example shows a patient's tumor signaling pathway was identified and treatment with drugs targeting the pathway led to no cancer metastasis. The approach aims to continue validating with more medical collaborators.
Construction of cancer pathways for personalized medicineAnton Yuryev
This document discusses constructing cancer pathways for personalized medicine using sub-network enrichment analysis (SNEA). SNEA calculates the transcriptional activity of upstream regulators using differentially expressed genes and regulatory knowledgebases. This identifies key expression regulators in specific cancer patients. Mapping these regulators onto known pathways builds personalized cancer pathways for each patient. Analyzing pathways from multiple patients provides insights into common cancer biology and identifies potential drug targets in a personalized manner.
Informa - Demonstrating Your PARP Inhibitor's ValueDan Ngo
The document discusses making a business case for a PARP inhibitor drug in the ovarian cancer market. It provides information from various data sources on competitor drugs and clinical trials, the size of the ovarian cancer market, sales forecasts for Lynparza and other PARP inhibitors, and deal values that phase 1 oncology drugs and PARP inhibitors have achieved when licensed.
There are several genomic tests that can help predict the risk of recurrence of early-stage breast cancer and determine the benefits of chemotherapy, including Oncotype DX, MammaPrint, Mammostrat, and Prosigna. Oncotype DX analyzes the activity of 21 genes and assigns a Recurrence Score between 0-100, with scores below 18 indicating a low risk cancer unlikely to benefit from chemotherapy. MammaPrint analyzes 70 genes to determine a low or high risk classification. Mammostrat measures levels of 5 genes to calculate a risk index score. Prosigna analyzes 58 genes to estimate the risk of distant recurrence within 10 years as low, intermediate, or high risk. Of the tests, Oncotype
In a narrow sense of cancer biomarker, it is limited to proteins the most used to challenge in the clinical applications, especially in the CAR-T therapy. Specifically, a cancer biomarker of the CAR-T provides the most prominent signal of cancer cells for distinguishing from normal cells and the most effective CAR T target for immune recognition and destruction. https://www.creative-biolabs.com/car-t/biomarker-identification-selection.htm
Speaker: Lisette Stork-Sloots, Sr Program Director at Agendia, discusses how their technology, MammaPrint was commercialized.
Part of Dx2010, a workshop at MaRS focused on best practices and regulatory considerations for developing gene-based diagnostic and prognostic tests.
The Stanford-Cancer Genome Atlas Portal Tutorialpantcga
The Stanford-Cancer Genome Atlas Portal allows users to explore clinical associations of cancer drivers in three main ways:
1. By searching a gene/miR/protein name to see associated clinical parameters or filtering by cancer type and clinical parameter.
2. By profiling genetic/proteomic changes between classes of a selected clinical parameter in a cancer type.
3. By testing the "two hit hypothesis" to see if two genetic/proteomic changes occur together more than expected by chance.
An Overview of Pancreatic Cancer - Creative BiolabsCreative-Biolabs
Pancreatic cancer is one of the malignant tumors with strong invasiveness, high degree of deterioration and low surgical resection rate in the digestive system. Optimizing early diagnosis and developing targeted therapy of pancreatic cancer are the key to improving the survival rate of patients. The slide named an overview of pancreatic cancer is created by Creative Biolabs who provides high-quality antibody production with advanced research tools, professional technical support, and rapid global delivery. In the slide, we will give you a comprehensive introduction to pancreatic cancer and its signaling pathways, diagnostics markers and targeted therapies, as well as Creative Biolabs’ antibody-related products and services. It is believed that you can fully understand how important it is to optimize early diagnosis and develop targeted drugs.
The document discusses several gene expression profiling tests for early breast cancer, including OncotypeDX, MammaPrint, and TAILORx. OncotypeDX analyzes the expression of 21 genes to calculate a recurrence score that predicts the likelihood of distant recurrence within 10 years for tamoxifen-treated patients. MammaPrint analyzes 70 genes to classify patients into low or high risk groups. The TAILORx clinical trial aims to determine which patients with early breast cancer and OncotypeDX scores of 11-25 benefit from chemotherapy using a randomized design.
Research aarkstore enterprise breast cancer therapies marketsNeel Terde
This document provides an overview and analysis of the breast cancer therapies market. It examines the major modalities used to treat breast cancer, including hormone therapy, surgery, radiation, chemotherapy, targeted therapy, and personalized medicine approaches. The report provides global, regional, and country-level breast cancer statistics. It also analyzes trends in the pharmaceutical market for breast cancer, including generics, branded drugs, hormones, and targeted therapies. Key factors shaping the market are discussed like reimbursement, regulations, and the shift toward personalized treatment.
AlphaImpactRx Barclays Oncology Webinar 1 Dec 2015Lesley Bailey
AlphaImpactRx and Barclays Capital conducted a webinar on the emerging dynamics of today’s US oncology market on Tuesday, December 1st from 12-1 pm EST.
Mark Purcell, head of Barclays global pharmaceutical equity research team and Stacy Mecham, SVP, Oncology Franchise at AlphaImpactRx presented the latest data in immuno-oncology, including late-breaking news on PD-L1 testing, as well as developing trends in breast cancer and CLL treatment to get you ready for the upcoming ASH and San Antonio Breast Cancer conferences.
Competition across the immuno-oncology battlefield is heating up behind the recent launches of Opdivo and Keytruda, and it promises to get more crowded in the near future. We’ll provide unique insight generated from the AlphaImpactRx point-of-care data to help you understand who’s gaining traction, and where it’s being gained, in both NSCLC and melanoma. We’ll provide a first look into the prevalence and influence of PD-LI testing in its early days, as well as a view of the latest treatment strategies emerging in the competitive breast cancer and CLL markets.
This document discusses using data from the Veterans Affairs (VA) healthcare system to conduct precision oncology research. It describes extracting data from the VA Corporate Data Warehouse, including clinical records from cancer registries and records of patients who received tumor sequencing and immunotherapy. The author builds a cohort of 330 non-small cell lung cancer patients who received immunotherapy before 2018 and had their cancer verified in the registry to study outcomes like the impact of PD-L1 expression on response to treatment. Challenges include lag times in cancer registry reporting and building a large enough cohort to draw powerful conclusions from retrospective analyses.
Us breast cancer therapy market opportunity analysisRajesh Sarma
"US Breast Cancer Therapy Market Opportunity Analysis" Report Highlight:
US Breast Cancer Incidence & Prevalence
US Breast Cancer Therapy Market Overview
US Breast Cancer Drug Clinical Pipeline by Company & Phase
US Breast Cancer Drug Clinical Pipeline: 251 Drugs
Majority Drugs in Phase-II Trials: 73 Drugs
Marketed Breast Cancer Drugs in US: 32 Drugs
Breast Cancer Patent Analysis
- The FDA has approved the site-agnostic cancer drugs Keytruda and Vitrakvi based on trials with very small numbers of patients for most tumor sites, often with 5 or fewer patients or even a single patient.
- Health technology assessment bodies will compare these site-agnostic drugs to existing therapies targeted to specific anatomical sites, which have more robust data, potentially affecting pricing and access.
- For some rare tumor sites like salivary gland cancer, favorable pricing and access for site-agnostic drugs may be possible, but access will likely be restricted for many other sites without larger clinical trials providing stronger evidence for each site.
This corporate presentation summarizes PharmaMar's pipeline and strategy:
- PharmaMar is a biotech company focused on developing marine-derived oncology drugs. It has a fully integrated platform from discovery to commercialization.
- The pipeline includes Yondelis® for soft tissue sarcoma and ovarian cancer, Aplidin® for multiple myeloma, and PM1183 which is being studied in small cell lung cancer, platinum-resistant ovarian cancer, and BRCA breast cancer.
- PM1183 has shown promising results in early clinical trials, achieving a 67% response rate in small cell lung cancer. Phase III trials are ongoing in platinum-resistant ovarian cancer.
Tumor markers in diagnosis and prognosis of colorectalkiran malbul
Tumor markers, also known as biomarkers, are substances produced by tumor cells or other cells in response to cancer. They can be found in bodily fluids and tissues. Some tumor markers are specific to certain cancers, like colorectal cancer, while others are associated with multiple cancer types. Tumor markers for colorectal cancer found in blood include CEA, CA 19-9, and circulating tumor cells, while those found in tumor tissue include MSI, BRAF and KRAS mutations, and p53 mutations. These markers can be used for screening, diagnosing, staging, prognosis, guidance, monitoring treatment response, and planning therapy. However, tumor markers lack specificity and sensitivity and may be elevated in non-
Breakthrough Nanoparticle Drug Delivery Platform Enabling Lead Compound nanoFenretinide (ST-001): SciTech Development presentation with a focus on pediatric oncology (cancer) including Ewing’s Sarcoma Family of Tumours (ESFT), leukemia - acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML); and, neuroblastoma. The pitch deck also includes a company overview, proprietary technology, lead drug ST-001 nanoparticle fenretinide, patents, addressable market sizes, competiton, key personnel, advisory board, drug product characteristics, fenretinide history, other cancer indications, investment opportunity and drug mechanism of action (MOA).
The document discusses efforts by the National Institutes of Health (NIH) and Food and Drug Administration (FDA) to advance personalized medicine through several initiatives:
1. Developing a more integrated pathway to connect target identification by researchers to drug approval to help fill the void of insufficient private sector interest in most new targets.
2. The TRND program will help accelerate development of drugs for rare and neglected diseases by funding preclinical development.
3. The FDA is developing standards to incorporate genetic information into drug and device development and using biomarkers to evaluate therapies through its Critical Path Initiative.
Use of open, curated variant databases: ethics? Liability? - Bartha KnoppersHuman Variome Project
Translation of genomics into medicine and drug development requires comprehensive, high-quality, genomic variant databases. To support translation, there is a movement towards sharing clinical annotations of variants (e.g., benign, unknown, pathogenic) internationally via open access. Despite the growing popularity of variant databases, ethical issues and liability risks have received scant attention. Ethical priorities for variant databases include 1) competence – ensuring that data is responsibly managed, curated, and used; 2) confidentiality – ensuring appropriate safeguards for patient data; 3) communication – clearly describing the purpose, quality standards, and data handling practices to contributing patients and potential users; and 4) continuous oversight to adapt database governance in a rapidly evolving environment. How can database managers fulfill these obligations when these responsibilities are increasingly distributed along the clinical pipeline? Legal issues include medical liability based on potential harm to patients; liability based on third-party intellectual property or privacy rights in the data; and regulatory risks as variant data is integrated into genetic tests or devices. Can these risks can be managed through appropriate governance structures – including adequate consents, access processes, contributor agreements, and disclaimers – while still facilitating sharing and clinical use?
The BRCA ShareTM Consortium is a public-private partnership that promotes sharing of BRCA genetic data. It has over 35,000 BRCA test results from US and French clinical labs. The goal is to accelerate BRCA research. It is a open user group co-founded by Inserm and Quest Diagnostics. BRCA ShareTM is well adopted internationally. In June 2016, it incorporated new data from private partners, increasing the number of known BRCA mutations. The consortium of French experts helps curate and reclassify variants of unknown significance based on multiple lines of evidence. This benefits all partners through improved annotation of shared variants.
The document discusses the use of genomics in early stage breast cancer treatment. It describes how genomics can provide personalized treatment by understanding each tumor's biology and risk of recurrence. Two multi-gene assays, Mammaprint and Oncotype DX, are discussed. Oncotype DX has been clinically validated to predict recurrence risk and chemotherapy benefit in node-negative patients. Studies also show it can predict outcomes for node-positive patients treated with tamoxifen. The results from these assays often change treatment decisions by identifying patients unlikely to benefit from chemotherapy.
Get the right cancer drug, at right TimeSubin Suresh
Mitra Biotech is a Boston and Bengaluru-based startup that is developing personalized cancer therapies. It focuses on testing drugs on recreated tumor microenvironments in the lab before human trials. This approach has higher success rates and lower toxicity than conventional trials. Mitra Biotech has raised over $27 million to develop these personalized therapies and diagnostics. Major challenges include high costs, ensuring data quality, and coordinating information between different treatment centers.
COTI-2 is a novel small molecule discovered by Critical Outcome Technologies Inc. that restores the function of mutant p53 proteins and negatively modulates the PI3K/AKT/mTOR cancer-related signaling pathway. It shows promise as an oral cancer therapy for cancers with p53 mutations or abnormalities in the PI3K/AKT/mTOR pathway, which include a broad range of common cancers. Preclinical studies demonstrate its safety and effectiveness against several cancer types. A Phase I clinical trial is currently underway for gynecological cancers.
CHEMSAS is a drug discovery platform that uses machine learning and algorithms to accelerate drug development and identify compounds with a higher likelihood of clinical success. ROSALIND is a smart data platform that analyzes a tumor's genetic profile and identifies potential treatment combinations tailored to restore normal cell signaling. Critical Outcome Technologies (COTI) is a clinical-stage biotech company focusing on novel cancer therapeutics discovered using CHEMSAS. COTI's lead candidates COTI-2 and COTI-219 are currently in clinical trials.
This professional profile is for Gail Donegan, who has over 10 years of experience in academic and clinical research. She has expertise in areas such as regenerative medicine, developmental toxicology, and stem cell biology. Currently she seeks senior scientific management opportunities in life sciences. Her most recent role was as a senior postdoctoral associate and team leader for an EU project studying the effects of antimalarial drugs on fetal development.
The Stanford-Cancer Genome Atlas Portal Tutorialpantcga
The Stanford-Cancer Genome Atlas Portal allows users to explore clinical associations of cancer drivers in three main ways:
1. By searching a gene/miR/protein name to see associated clinical parameters or filtering by cancer type and clinical parameter.
2. By profiling genetic/proteomic changes between classes of a selected clinical parameter in a cancer type.
3. By testing the "two hit hypothesis" to see if two genetic/proteomic changes occur together more than expected by chance.
An Overview of Pancreatic Cancer - Creative BiolabsCreative-Biolabs
Pancreatic cancer is one of the malignant tumors with strong invasiveness, high degree of deterioration and low surgical resection rate in the digestive system. Optimizing early diagnosis and developing targeted therapy of pancreatic cancer are the key to improving the survival rate of patients. The slide named an overview of pancreatic cancer is created by Creative Biolabs who provides high-quality antibody production with advanced research tools, professional technical support, and rapid global delivery. In the slide, we will give you a comprehensive introduction to pancreatic cancer and its signaling pathways, diagnostics markers and targeted therapies, as well as Creative Biolabs’ antibody-related products and services. It is believed that you can fully understand how important it is to optimize early diagnosis and develop targeted drugs.
The document discusses several gene expression profiling tests for early breast cancer, including OncotypeDX, MammaPrint, and TAILORx. OncotypeDX analyzes the expression of 21 genes to calculate a recurrence score that predicts the likelihood of distant recurrence within 10 years for tamoxifen-treated patients. MammaPrint analyzes 70 genes to classify patients into low or high risk groups. The TAILORx clinical trial aims to determine which patients with early breast cancer and OncotypeDX scores of 11-25 benefit from chemotherapy using a randomized design.
Research aarkstore enterprise breast cancer therapies marketsNeel Terde
This document provides an overview and analysis of the breast cancer therapies market. It examines the major modalities used to treat breast cancer, including hormone therapy, surgery, radiation, chemotherapy, targeted therapy, and personalized medicine approaches. The report provides global, regional, and country-level breast cancer statistics. It also analyzes trends in the pharmaceutical market for breast cancer, including generics, branded drugs, hormones, and targeted therapies. Key factors shaping the market are discussed like reimbursement, regulations, and the shift toward personalized treatment.
AlphaImpactRx Barclays Oncology Webinar 1 Dec 2015Lesley Bailey
AlphaImpactRx and Barclays Capital conducted a webinar on the emerging dynamics of today’s US oncology market on Tuesday, December 1st from 12-1 pm EST.
Mark Purcell, head of Barclays global pharmaceutical equity research team and Stacy Mecham, SVP, Oncology Franchise at AlphaImpactRx presented the latest data in immuno-oncology, including late-breaking news on PD-L1 testing, as well as developing trends in breast cancer and CLL treatment to get you ready for the upcoming ASH and San Antonio Breast Cancer conferences.
Competition across the immuno-oncology battlefield is heating up behind the recent launches of Opdivo and Keytruda, and it promises to get more crowded in the near future. We’ll provide unique insight generated from the AlphaImpactRx point-of-care data to help you understand who’s gaining traction, and where it’s being gained, in both NSCLC and melanoma. We’ll provide a first look into the prevalence and influence of PD-LI testing in its early days, as well as a view of the latest treatment strategies emerging in the competitive breast cancer and CLL markets.
This document discusses using data from the Veterans Affairs (VA) healthcare system to conduct precision oncology research. It describes extracting data from the VA Corporate Data Warehouse, including clinical records from cancer registries and records of patients who received tumor sequencing and immunotherapy. The author builds a cohort of 330 non-small cell lung cancer patients who received immunotherapy before 2018 and had their cancer verified in the registry to study outcomes like the impact of PD-L1 expression on response to treatment. Challenges include lag times in cancer registry reporting and building a large enough cohort to draw powerful conclusions from retrospective analyses.
Us breast cancer therapy market opportunity analysisRajesh Sarma
"US Breast Cancer Therapy Market Opportunity Analysis" Report Highlight:
US Breast Cancer Incidence & Prevalence
US Breast Cancer Therapy Market Overview
US Breast Cancer Drug Clinical Pipeline by Company & Phase
US Breast Cancer Drug Clinical Pipeline: 251 Drugs
Majority Drugs in Phase-II Trials: 73 Drugs
Marketed Breast Cancer Drugs in US: 32 Drugs
Breast Cancer Patent Analysis
- The FDA has approved the site-agnostic cancer drugs Keytruda and Vitrakvi based on trials with very small numbers of patients for most tumor sites, often with 5 or fewer patients or even a single patient.
- Health technology assessment bodies will compare these site-agnostic drugs to existing therapies targeted to specific anatomical sites, which have more robust data, potentially affecting pricing and access.
- For some rare tumor sites like salivary gland cancer, favorable pricing and access for site-agnostic drugs may be possible, but access will likely be restricted for many other sites without larger clinical trials providing stronger evidence for each site.
This corporate presentation summarizes PharmaMar's pipeline and strategy:
- PharmaMar is a biotech company focused on developing marine-derived oncology drugs. It has a fully integrated platform from discovery to commercialization.
- The pipeline includes Yondelis® for soft tissue sarcoma and ovarian cancer, Aplidin® for multiple myeloma, and PM1183 which is being studied in small cell lung cancer, platinum-resistant ovarian cancer, and BRCA breast cancer.
- PM1183 has shown promising results in early clinical trials, achieving a 67% response rate in small cell lung cancer. Phase III trials are ongoing in platinum-resistant ovarian cancer.
Tumor markers in diagnosis and prognosis of colorectalkiran malbul
Tumor markers, also known as biomarkers, are substances produced by tumor cells or other cells in response to cancer. They can be found in bodily fluids and tissues. Some tumor markers are specific to certain cancers, like colorectal cancer, while others are associated with multiple cancer types. Tumor markers for colorectal cancer found in blood include CEA, CA 19-9, and circulating tumor cells, while those found in tumor tissue include MSI, BRAF and KRAS mutations, and p53 mutations. These markers can be used for screening, diagnosing, staging, prognosis, guidance, monitoring treatment response, and planning therapy. However, tumor markers lack specificity and sensitivity and may be elevated in non-
Breakthrough Nanoparticle Drug Delivery Platform Enabling Lead Compound nanoFenretinide (ST-001): SciTech Development presentation with a focus on pediatric oncology (cancer) including Ewing’s Sarcoma Family of Tumours (ESFT), leukemia - acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML); and, neuroblastoma. The pitch deck also includes a company overview, proprietary technology, lead drug ST-001 nanoparticle fenretinide, patents, addressable market sizes, competiton, key personnel, advisory board, drug product characteristics, fenretinide history, other cancer indications, investment opportunity and drug mechanism of action (MOA).
The document discusses efforts by the National Institutes of Health (NIH) and Food and Drug Administration (FDA) to advance personalized medicine through several initiatives:
1. Developing a more integrated pathway to connect target identification by researchers to drug approval to help fill the void of insufficient private sector interest in most new targets.
2. The TRND program will help accelerate development of drugs for rare and neglected diseases by funding preclinical development.
3. The FDA is developing standards to incorporate genetic information into drug and device development and using biomarkers to evaluate therapies through its Critical Path Initiative.
Use of open, curated variant databases: ethics? Liability? - Bartha KnoppersHuman Variome Project
Translation of genomics into medicine and drug development requires comprehensive, high-quality, genomic variant databases. To support translation, there is a movement towards sharing clinical annotations of variants (e.g., benign, unknown, pathogenic) internationally via open access. Despite the growing popularity of variant databases, ethical issues and liability risks have received scant attention. Ethical priorities for variant databases include 1) competence – ensuring that data is responsibly managed, curated, and used; 2) confidentiality – ensuring appropriate safeguards for patient data; 3) communication – clearly describing the purpose, quality standards, and data handling practices to contributing patients and potential users; and 4) continuous oversight to adapt database governance in a rapidly evolving environment. How can database managers fulfill these obligations when these responsibilities are increasingly distributed along the clinical pipeline? Legal issues include medical liability based on potential harm to patients; liability based on third-party intellectual property or privacy rights in the data; and regulatory risks as variant data is integrated into genetic tests or devices. Can these risks can be managed through appropriate governance structures – including adequate consents, access processes, contributor agreements, and disclaimers – while still facilitating sharing and clinical use?
The BRCA ShareTM Consortium is a public-private partnership that promotes sharing of BRCA genetic data. It has over 35,000 BRCA test results from US and French clinical labs. The goal is to accelerate BRCA research. It is a open user group co-founded by Inserm and Quest Diagnostics. BRCA ShareTM is well adopted internationally. In June 2016, it incorporated new data from private partners, increasing the number of known BRCA mutations. The consortium of French experts helps curate and reclassify variants of unknown significance based on multiple lines of evidence. This benefits all partners through improved annotation of shared variants.
The document discusses the use of genomics in early stage breast cancer treatment. It describes how genomics can provide personalized treatment by understanding each tumor's biology and risk of recurrence. Two multi-gene assays, Mammaprint and Oncotype DX, are discussed. Oncotype DX has been clinically validated to predict recurrence risk and chemotherapy benefit in node-negative patients. Studies also show it can predict outcomes for node-positive patients treated with tamoxifen. The results from these assays often change treatment decisions by identifying patients unlikely to benefit from chemotherapy.
Get the right cancer drug, at right TimeSubin Suresh
Mitra Biotech is a Boston and Bengaluru-based startup that is developing personalized cancer therapies. It focuses on testing drugs on recreated tumor microenvironments in the lab before human trials. This approach has higher success rates and lower toxicity than conventional trials. Mitra Biotech has raised over $27 million to develop these personalized therapies and diagnostics. Major challenges include high costs, ensuring data quality, and coordinating information between different treatment centers.
COTI-2 is a novel small molecule discovered by Critical Outcome Technologies Inc. that restores the function of mutant p53 proteins and negatively modulates the PI3K/AKT/mTOR cancer-related signaling pathway. It shows promise as an oral cancer therapy for cancers with p53 mutations or abnormalities in the PI3K/AKT/mTOR pathway, which include a broad range of common cancers. Preclinical studies demonstrate its safety and effectiveness against several cancer types. A Phase I clinical trial is currently underway for gynecological cancers.
CHEMSAS is a drug discovery platform that uses machine learning and algorithms to accelerate drug development and identify compounds with a higher likelihood of clinical success. ROSALIND is a smart data platform that analyzes a tumor's genetic profile and identifies potential treatment combinations tailored to restore normal cell signaling. Critical Outcome Technologies (COTI) is a clinical-stage biotech company focusing on novel cancer therapeutics discovered using CHEMSAS. COTI's lead candidates COTI-2 and COTI-219 are currently in clinical trials.
This professional profile is for Gail Donegan, who has over 10 years of experience in academic and clinical research. She has expertise in areas such as regenerative medicine, developmental toxicology, and stem cell biology. Currently she seeks senior scientific management opportunities in life sciences. Her most recent role was as a senior postdoctoral associate and team leader for an EU project studying the effects of antimalarial drugs on fetal development.
This study validated a rat pharmacokinetic/pharmacodynamic model to rapidly assess drug candidates intended to inhibit tumor necrosis factor-alpha (TNFα) synthesis or release for inflammatory diseases. Lipopolysaccharide was administered to rats to induce TNFα production, and a selective TNFα converting enzyme inhibitor was used as a model compound. The model demonstrated an ability to correlate plasma drug concentrations with inhibition of lipopolysaccharide-induced TNFα levels in vivo. Areas under the concentration-time curves were calculated for the drug and TNFα to determine the overall percentage reduction of TNFα release. This PK/PD model provides integrated information on pharmacokinetics and in vivo potency of test articles.
Immunobiology and new challenges in drug developmentDr Kurt Sales
This document provides an agenda and background information for an immunobiology day event hosted by Charles River Laboratories. The event will cover regulatory frameworks for developing biological therapeutics, suitable animal species for testing, bioanalysis techniques, immunophenotyping assays, and challenges of pharmacokinetics for large molecules. Speakers will discuss regulatory guidelines, validating cell-based assays, analyzing macromolecules, using nonhuman primates in safety testing, and strategies for drug metabolism and pharmacokinetics research on large molecules. Attendees will learn about typical development programs and challenges in preclinical testing of biotherapeutics.
Raymond J. Winquist is an experienced research leader with over 30 years of experience in drug discovery. He has held senior leadership roles at several large pharmaceutical companies and biotechs, managing departments with budgets over $25 million. His expertise is in pharmacology, molecular and cellular biology, and overseeing diverse research platforms. He has progressed multiple drug candidates into clinical trials across various therapeutic areas such as oncology, neurology, and inflammation.
The document summarizes interactions and meetings related to developing treatments for Chagas disease. It notes 75 total interactions in pharma, Chagas KOLs, veterinary, and diagnostics. Key mentors and advisors are listed. The remainder of the document outlines progress in defining the problem and opportunity, building an ecosystem of partners, evaluating product and market options, developing a business model and strategy, and achieving investor readiness.
This document provides a summary of Darlene Coleman Deecher's career experience and qualifications. She has over 25 years of experience in pharmaceutical research and development, including roles in drug discovery, preclinical and clinical development, and product launch. Her educational background includes a PhD in Toxicology/Pharmacology and she has worked in leadership roles at Wyeth Research and Abbott Laboratories, managing teams in areas like women's health and neuroscience.
This document is a curriculum vitae for Hui Zhang, a professor at Johns Hopkins University School of Medicine. It lists his current appointments, education history, professional experience, and publications. Specifically, it details that he is currently a professor in the Department of Pathology at JHU and director of the Mass Spectrometry Core Facility. It provides information on his education from Beijing University and University of Pennsylvania. It also lists over 45 publications in peer-reviewed journals related to proteomics and mass spectrometry research.
This document is a curriculum vitae for Dr. Michael S. Lauer that provides biographical information over 10 pages. It includes his education history, postdoctoral training, licensure and certifications, appointments, awards and honors, memberships, research interests, teaching experience, and publications. He is currently the Director of the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute at the NIH in Bethesda, Maryland. The CV demonstrates an accomplished career in cardiology, epidemiology, and biomedical research leadership.
Dr. David Banji has over 27 years of experience in teaching, research, and academic administration in pharmacology and toxicology. He received his B.Pharm, M.Pharm, and Ph.D from universities in India and has held positions as Principal and Director of academic institutions. He has published over 180 research papers, supervised many M.Pharm and Ph.D students, and received multiple grants and awards for his work in education and research.
Dr. Hager 2016 Presentation The Challenges of Achieving Early Efficacy in Cli...Dr. Martin Hager, MBA
This document summarizes information about the development of DS-6051, a ROS1/NTRK dual kinase inhibitor being developed by Daiichi-Sankyo for the treatment of cancers. It discusses challenges in early drug development including predicting phase II success. It provides details on DS-6051's mechanism of action, differentiation from other drugs, ongoing clinical trial design incorporating screening approaches, safety and efficacy results from the phase I trial, and plans for phase I expansion. The document covers multiple topics relating to DS-6051's development path and strategies to incorporate early efficacy data.
Actualización en el abordaje terapéutico ante un cáncer colorrectal metastásicoMauricio Lema
Ponencia en el VII Congreso internacional de coloproctología, Bogotá, 18.08.2016. Con énfasis en los estudios recientes en terapia antiangiogénica, y el impacto del lado del primario en el pronóstico (y aspectos predictivos) de la enfermedad metastásica.
COTI-2 is a small molecule discovered by Critical Outcome Technologies to reactivate mutant p53 through zinc chelation. It demonstrates strong efficacy against a wide range of p53 mutations in vitro and significant tumor growth inhibition in vivo without inducing resistance. Further studies confirmed COTI-2's p53-dependent mechanism of action and ability to modulate the PI3K/AKT pathway. An IND filing is planned in mid-2014 to study COTI-2 in gynecological cancers.
This presentation contains an overview of the scientific and business update provided by management during Critical Outcome Technologies' 2017 Annual General and Special Meeting of Shareholders on December 20, 2017.
Webinar by BIS Research on Precision Oncology BiomarkersBIS Research Inc.
Precision oncology biomarkers are essential tools for tailoring cancer treatment to individual patients, as they provide insights into tumor biology and guide the selection of targeted therapies.
BIS conducted a deep intelligence webinar on the state-of-the-art technologies and emerging strategies used through the precision oncology biomarkers.
Join Fight CRC in a webinar about biomarkers. In this session, Dr. Chris Lieu will focus the discussion on the NTRK biomarker, in addition to ctDNA, and Next-Generation Sequencing.
El futuro del tratamiento del cáncer renal metastásico: inmunoterapia y terap...Mauricio Lema
Ponencia en el primer simposio de la Asociación Colombiana de Hematología y Oncología (ACHO) de cáncer genitourinario, Bogotá, septiembre 23 y 24 de 2016.
An overview of Critical Outcome Technologies' lead cancer drug candidate, COTI-2, which represents a potential breakthrough treatment for many types of cancer. Critical Outcome Technologies is listed on the TSX Venture Exchange under the symbol COT.
Senesco Technologies is developing a gene regulation technology to treat cancer. They are running a Phase 1b/2a clinical trial of their lead product, SNS01-T, to treat B-cell cancers like multiple myeloma and lymphoma. Preclinical studies show SNS01-T significantly inhibits tumor growth and improves survival in mouse models of these cancers. The presentation provides an overview of Senesco's technology, clinical trial status, financial information, and development plans to advance SNS01-T and expand to additional cancer indications.
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2. 2
• MEETING CALLED TO ORDER – Mr. John Drake, Chairman
• CHAIRMAN’S OPENING REMARKS
• APPOINTMENT OF THE SECRETARY FOR THE MEETING
• APPOINTMENT OF THE SCRUTINEER & SCRUTINEER’S REPORT
• READING OF THE NOTICE OF THE MEETING
• READING OF THE MINUTES OF THE ANNUAL MEETING OF SHAREHOLDERS OF OCTOBER 15/15
• FINANCIAL STATEMENTS
• FIX THE NUMBER OF DIRECTORS
• ELECTION OF THE DIRECTORS
• APPOINTMENT OF THE AUDITOR AND AUTHORITY TO FIX THEIR REMUNERATION
• APPROVAL OF DISCRETIONARY SHARE CONSOLIDATION
• APPROVAL OF AMENDMENTS TO THE ORGANIZATIONAL BY-LAW
• APPROVAL OF AMENDMENTS TO THE SHAREHOLDER RIGHTS PLAN
• APPROVAL OF AMENDMENTS TO THE STOCK OPTION PLAN
• APPROVAL OF CONTINUATION OF THE STOCK OPTION PLAN AS A ROLLING PLAN
• BUSINESS AND SCIENTIFIC UPDATE PRESENTATION – Dr. W. Danter, CEO; Ms. A. Silva, President
• OTHER BUSINESS
Meeting Agenda
4. 4
When used anywhere in this presentation, whether oral or written, the words expects,
believes, anticipates, estimates and similar expressions are intended to identify forward-
looking statements. Forward-looking statements may include statements addressing
future financial and operating results of Critical Outcome Technologies Inc. (COTI).
COTI bases these forward-looking statements on its current expectations about future
events. Such statements are subject to risks and uncertainties including, but not limited
to, the successful implementation of COTI’s strategic plans, the acceptance of new
products, the obsolescence of existing products, the resolution of potential patent
issues, competition, changes in economic conditions, and other risks described in COTI’s
public documents such as press releases and filings with the Toronto Stock Exchange and
the Ontario Securities Commission.
All forward-looking statements are qualified in their entirety by the cautionary
statements included in this document and such filings. These risks and uncertainties
could cause actual results to differ materially from results expressed or implied by
forward-looking statements contained in this presentation. These forward-looking
statements speak only as of the date of this presentation.
Disclaimer
5. 5
• Clinical stage biotech company
focused on the development of novel
therapeutics for the treatment of
cancer
• Pipeline of internally developed
compounds
• CHEMSAS platform – in silico high
throughput screening for molecule
identification
• ROSALIND technology – genomics
profiling for personalized oncology
care
• Two offices: London, ON and Boston,
MA
TSX-V: COT
OTCQB: COTQF
Company and Pipeline Synopsis
7. • Oral small molecule compound that functions via a novel
mechanism of action that reactivates the tumor suppressor
function of p53
– Mutant p53: single most important cancer causing gene mutation
known
• > 50% of all human cancers
• Active against common cancers in multiple preclinical models
– High oral bioavailability and effective at low doses in preclinical models
– Low toxicity in preclinical development
• Currently in an open label, multi-site Phase I in gynecological
malignancies
– Opportunity for a novel therapy as a single agent and combination
therapy
7
COTI-2 Synopsis
8. 8
• The centrality of p53 in human cancer makes it a potentially effective target for
cancer therapy development
– In response to cellular stress, wild-type p53 induces cell cycle arrest and/or apoptotic
cell death1
– Mutant p53 promotes tumor formation (loss of tumor suppressor function)2
• TP53 is the most frequently mutated gene in human cancer with mutation
frequencies ranging from 38% to 96%1
• COTI-2 induces a wild-type-like conformational change in the p53 mutant protein
that restores sequence-specific p53 transcription3
1Levin AJ & Oren M (2009). Nature Rev Cancer, 9: 749-758.
2Ozaki T & Nakagawara A (2011). J Biomed Biotech, 2011: 603925, 1-13.
3Yu X et al (2012) Cancer Cell, 21: 614-625.
mutp53
mutp53
Sequence-specific
transactivation defective
Conformational change to a
more wild-type configuration
Restoration of sequence-specific
transcriptional activity
Apoptosis,
growth arrest,
senescence
mutp53
Drug Drug
COTI-2: Mechanism of Action
9. 9
• COTI-2 induces a ‘wild-type-like’ conformational change in mutant p53R175H in TOV-112D
ovarian cancer cell line but has no effect on p53WT conformation in H460 NSCLC cell line
• Similar results with multiple p53 mutant proteins in HCT-116 constructs
0
20
40
60
80
100
120
TOV-112D H460
MeanFluorescenceIntensity
(ArbitraryUnits)
Cell Line
Mutant p53 Levels in Presence/Absence of COTI-2
Control
COTI-2
0
20
40
60
80
100
120
TOV-112D H460
MeanFluorescenceIntensity
(ArbitraryUnits)
Cell Line
Wild-type p53 Levels in the Presence/Absence of COTI-2
Control
COTI-2
• (*) Significant difference in p53 protein levels between COTI-2 treated and untreated cells (control)
*
*
James Koropatnick, LRCC, London, ON.
Conformational Change Induced in p53 by COTI-2
10. 10
• COTI-2 induced no significant resistance through 5 generations, whereas cisplatin and
paclitaxel induce significant increases in IC50 after the first generation of selection
• COTI-2 induced no significant cross-resistance in cisplatin- and paclitaxel-resistant SCLC cell
lines
0.0
1.0
2.0
3.0
4.0
Parental
cells
Round 1
selection
Round 2
selection
Round 3
selection
Round 4
selection
IC50Ratio
Acquired Resistance in the DMS-153 SCLC Cell Line
COTI-2
Cisplatin
Paclitaxel
*
*
*
*
*
* *
*
0.0
2.0
4.0
6.0
8.0
10.0
Parental
cells
Round 1
selection
Round 2
selection
Round 3
selection
Round 4
selection
IC50Ratio
Acquired resistance in the SHP-77 SCLC Cell Line
COTI-2
Cisplatin
Paclitaxel
*
*
*
*
* *
*
0
1
2
3
4
A549 - CP Resist DMS153 - CP
Resist
SHP77 - CP Resist
IC50(FoldChangeRelative
toParentalCells)
Sensitivity to cisplatin-resistant cell lines
COTI-2
Cisplatin
0
2
4
6
8
10
A549 - PAC
Resist
DMS153 - PAC
Resist
SHP77 - PAC
Resist
IC50(FoldChangeRelative
toParentalCells)
Sensitivity to paclitaxel-resistant cell lines
COTI-2
Paclitaxel
*
*
*
*
*
*
James Koropatnick, LRCC, London, ON.
No Significant Resistance or Cross-Resistance
11. 11
• COTI-2 administered IV and PO produced a significant tumor growth inhibition as a single
agent in an OVCAR-3 ovarian cancer xenograft model
– In fact, COTI-2 caused significant and complete tumor shrinkage when administered IV (p<0.01);
treatment of Group 3 animals stopped since tumors were rapidly shrinking
0
50
100
150
200
0 5 9 16 23 30 37 44 51 61
TumorVolume(mm3)
Study Day
Effect of IV Treatment on OVCAR-3 Tumor Volume
Group 1 = Vehicle IV
Group 2 = COTI-2 20mg/kg IV
Group 3 = COTI-2 40mg/kg IV
0
50
100
150
200
250
0 5 9 16 23 30 37 44 51 61
TumorVolume(mm3)
Study Day
Effect of PO Treatment on OVCAR-3 Tumor Volume
Group 4 = Vehicle PO
Group 5 = COTI-2 75mg/kg PO
Group 6 = COTI-2 100mg/kg PO
* *
* * * *
* *
* * * * * * * * *
*
* * * *
*
*
* * * * * * * *
James Koropatnick, LRCC, London, ON.
Significant Tumor Growth Inhibition as a Single Agent
12. 12
• COTI-2 administered PO caused significant tumor growth inhibition in the HCT-116 p53G245C
colorectal cancer cell line construct
• No effect on tumor growth observed with HCT-116 (GFP) construct without p53 mutation
0
100
200
300
400
500
600
700
1 4 7 10 14
TumorVolume(mm3)
Study Day
Effect of Treatment on HCT-116 (p53 G245C) Tumor Volume
Vehicle Control
COTI-2 (30 mg/kg)
COTI-2 (75 mg/kg)
0
200
400
600
800
1000
1200
1 4 7 10 14 17
TumorVolume(mm3)
Study Day
Effect of Treatment on HCT-116 (GFP) Tumor Volume
Vehicle Control
COTI-2 (75 mg/kg)
*
*
*
*
Gordon Mills, U of Texas, MDACC, Houston, TX.
p53 Mutant-specific Tumor Growth Inhibition as a Single Agent
13. 13
• COTI-2 in combination with cisplatin (CDDP) has a synergistic effect as indicated by a
combination index1 (CI) < 1.0 in the PCI13 p53G245D construct
• Similar results were obtained with paclitaxel, carboplatin, erlotinib, and cetuximab
COTI-2 and CDDP Curves
1Chou TC &Talalay P (1983) Trends Pharmacol Sci. 4: 450-454.
Jeffrey Myers, U of Texas, MDACC, Houston, TX.
Effectiveness of Cisplatin Enhanced in p53 Mutant Cells
14. 14
• COTI-2 whether as a single agent or in combination with cisplatin produced significant tumor
growth inhibition relative to untreated controls in the PCI13 pG245D head and neck cancer
xenograft models
• Cisplatin treatment alone did not yield significant tumor growth inhibition
* * * * *
* * * * *
* * *
Jeffrey Myers, U of Texas, MDACC, Houston, TX.
Significant Tumor Growth Inhibition in Combination with Cisplatin
15. 15
• COTI-2 significantly improves in vitro response to radiation
• The addition of COTI-2 sensitized head and neck cancer cell lines to radiation in a dose-
dependent manner irrespective of TP53 status
Dose-Dependent Curves
Jeffrey Myers, U of Texas, MDACC, Houston, TX.
Sensitization of p53 Mutant Cells to Radiation
16. 16
No Significant COTI-2 Associated In Vivo Toxicity
• COTI-2 administered IV or PO up to 61 days in an OVCAR-3 ovarian cancer tumor model had
no significant effect on mouse weight
• Similar observations in multiple mouse models
15.00
20.00
25.00
0 5 9 16 23 30 40 47 54 61
Weight(g)
Study Day
Effect of Treatment on Mouse Weight in OVCAR-3 Tumor Model
Vehicle IV
COTI-2 20mg/kg IV
COTI-2 40mg/kg IV
Vehicle PO
COTI-2 75 mg/kg PO
COTI-2 100 mg/kg PO
18. 18
• COTI-219 inhibits KRAS activation
– Inhibition is time- and concentration-dependent
– This inhibitory effect is also evident in downstream targets
• Lymphoma
Experimental design
• Millipore’s Ras Activation ELISA Assay Kit was utilized to detect KRAS
and other relevant proteins in the presence/absence of COTI-219
• Cell viability was assessed using the PrestoBlue® assay
HeyA8 Cell Line OVCAR8 Cell Line
CELL LINE
DURATION OF COTI-219
EXPOSURE (days)
IC50 (nM)
HeyA8
1 10,000
3 72
5 50
7 55
CELL LINE
DURATION OF COTI-219
EXPOSURE (days)
IC50 (nM)
OVCAR8
1 10,000
3 N/A
5 79
7 47
COTI-219 Inhibits KRAS Activation
19. 19
• COTI-219 significantly inhibits tumor growth in colorectal cancer cell lines with a KRAS
mutation
– HCT-15 (KRASG13D) and SW620 (KRASG12V) tumor growth was inhibited by COTI-219 at approximately
50% and 25%, respectively
– TGI likely to be much higher in cell lines expressing high levels of KRAS
Experimental design
• HCT-15 and SW620 human tumor cells inoculated subcutaneously in right flank of female athymic mice (NCR-nu)
• Groups of 10-12 mice each were treated PO with COTI-219 (150 or 75 mg/kg ) or phosphate-citrate buffer vehicle control every other day 3
times per week for roughly 25 days
• Tumor weights were graphed as means (±SE) and significant difference between groups was determined using Student’s T-test (p<0.05)
COTI-219 Significantly Inhibits KRAS Mutant Tumor Growth
20. 20
• COTI-219 demonstrates single agent efficacy greater than standard chemotherapeutics in SHP-
77 (KRASG12V) mouse xenograft model
• COTI-219 significantly inhibits tumor growth in the SHP-77 cells relative to vehicle control
Experimental Design
• SHP-77 human tumor cells inoculated
subcutaneously in right flank of female
athymic mice (NCR-nu)
• Groups of 10 mice each were treated IP
with varying doses of COTI-219 (4 mg/kg
every 2 days), taxotere (12.5 mg/kg
every 2 days), cisplatin (3.0 mg/kg once
per week), and 0.9% saline vehicle
• Mean tumor volumes at day 38 were
graphed
Effect of Treatment on Tumor Volume
TumorVolume(mm3)
Test Compound
TGI~80%
* All animals died
COTI-219 Significantly Inhibits KRAS Mutant Tumor Growth
22. 22
Protocol Title A PHASE 1 STUDY OF COTI-2 FOR THE TREATMENT OF ADVANCED OR RECURRENT GYNECOLOGIC MALIGNANCIES
Study Sites MD Anderson Cancer Center, Houston, TX Northwestern University Memorial Hospital, Chicago, IL
Principal
Investigators
Dr. Shannon Westin Dr. Wilberto Neives-Niera
Study Phase Phase 1
Objective Primary
• To evaluate the safety and tolerability of COTI-2 in patients with advanced or recurrent gynecologic
malignancies.
• To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of COTI-2 for the
treatment of patients with advanced or recurrent gynecologic malignancies.
Secondary
• To evaluate the pharmacokinetics of COTI-2 at all dose levels in patients with advanced or recurrent gynecologic
malignancies.
• To estimate the clinical activity of COTI-2 at all dose levels and the RP2D in patients with advanced or recurrent
gynecologic malignancies by response rate (Response Evaluation Criteria In Solid Tumors [RECIST] v1.1 criteria) and
the progression-free survival (PFS) rate at 6 months.
• To estimate the response duration for COTI-2 at all dose levels and the RP2D in patients with advanced or
recurrent gynecologic malignancies.
Exploratory
• To determine if baseline molecular aberrations, including p53 mutation, correlate with activity of COTI-2 in
advanced or recurrent gynecologic malignancies.
• To evaluate pharmacodynamic markers of COTI-2 activity at all dose levels and at the RP2D in patients with
advanced or recurrent gynecologic malignancies.
Patient Population • Females with ovarian, fallopian tube, primary peritoneal, endometrial or cervical cancer that is recurrent,
metastatic, or unresectable and for which no effective or curative measures exist
Sample Size • Maximum 46 patients • Dose Escalation Phase: up to
36 patients (up to 6 cohorts)
• Dose Expansion Phase: 10
patients with ovarian cancer
(one cohort)
COTI2-101 Study Summary
23. • Regular updates as each cohort commences dosing with Cohort 3
announced in July 2016
– Announcement of dose escalation is the only “releasable” information during
this clinical phase
• February/March 2017 – preliminary results on the safety and clinical
activity of COTI-2
• First half of 2017 – additional multi center clinical trial programs:
– Recurrent Head and Neck Squamous Cell cancer (HNSCC)
– Li-Fraumeni Syndrome (LFS)
• Final trial results and conclusions
– Mid 2017 - gynecological phase
– Late 2017 - expansion phase
23
Anticipated COTI2-101 Clinical Trial News Flow
25. 25
DRUG COTI-2 Kevetrin APR-246 / PRIMA-1MET
COMPANY
Critical Outcome
Technologies Inc.
Cellceutix Corp Aprea
MECHANISM OF
ACTION
Targets mutant p53
(restoration of wild-type
p53 conformation and
activity)
Targets wild-type and
mutant p53 (MDM2-
related mechanism)
Targets mutant p53
(restoration of wild-type
p53 conformation and
activity)
IN VITRO EFFICACY
Most potent (nanomolar
range of activity)
Least potent (activity
>100 µM)
Much less potent than
COTI-2 (activity in high
µM range)
CLINICAL PHASE
OF DEVELOPMENT
Phase 1 Phase 1 Phase 1/2
INDICATIONS Gynecological
malignancies (first
patient in February 2016)
Solid tumors (complete
with safety established,
but PK under MEC)
Hematological
malignancies and
prostate cancer (phase
1/2 completed)
Competitor Comparison to COTI-2
27. 27
Granted FDA orphan drug status for ovarian cancer
Appointed experienced Scientific Advisory Board (SAB)
Received Investigational New Drug Application (IND) approval
Filed for FDA orphan drug status for Li-Fraumeni syndrome
Commenced patient dosing of Phase 1 clinical trial at MDACC
Published first scientific article in Oncotargets
Activated second clinical trial site at NWU
Initiated third patient cohort of Phase 1 clinical trial
Recap of Fiscal 2016 Corporate Objectives
28. 28
Opened US office (Boston, MA) in Aug 2016
• Broaden the potential for COTI-2 in multiple additional clinical indications
and combination therapies
Designate next preclinical candidate for clinical development
• Establish collaborations/partnerships for COTI-2, pipeline programs and other
technologies
• Strengthen the balance sheet to execute on the strategy
• Obtain Li-Fraumeni (or other sarcoma indication) orphan drug status
Fiscal 2017 Corporate Objectives
29. Pursue Multiple Indications/Combinations with COTI-2
• Additional multi center clinical trial programs
– Recurrent Head and Neck Squamous Cell cancer (HNSCC)
SPORE grant submitted with MDACC
• Trial anticipated to commence in early-mid 2017
– Li-Fraumeni Syndrome (LFS)
• Exploring clinical trial design with key opinion leaders (KOLs) and Scientific
Advisory Board (SAB)
• Rhabdomyosarcoma
• Adult and pediatric soft tissue sarcoma
• Trial anticipated to commence in mid 2017
– Combination trials
• COTI-2 synergizes with many first line agents including Cisplatin
• COTI-2 sensitizes HNSCC cell lines to radiation therapy
• Combination trials with COTI-2 plus Cisplatin or radiation are being planned
29
30. 30
• Chemistry
– Small molecule, easy to synthesize (3 steps)
• MOA
– COTI-219 docks in KRAS allosteric pocket at two sites
– COTI-219 inhibits the activation of KRAS
– COTI-219 sensitivity is correlated with KRAS expression levels
• Efficacy
– COTI-219 has IC50’s in the nanomolar range in multiple human cancer cell lines, particularly
in colorectal cancer
– No significant acquired or cross resistance with COTI-219
– COTI-219 induced significant tumor growth inhibition in the SHP-77 (SCLC), HCT-15
(colorectal cancer) and SW620 (colorectal cancer) tumor models
• ADME-Tox
– Good in vitro metabolic stability
– Pharmacokinetics suggests once a day dosing
• Intellectual property
– Issued composition of matter patents
Next Clinical Candidate - COTI-219
31. 31
Next Clinical Candidate - COTI-219
2016 Q4 2017 Q1 2017 Q2 2017 Q3 2017 Q4
Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
CHEMISTRY MANUFACTURING CONTROLS
DRUG SUBSTANCE
Manufacturing & Analytical Method
Testing & Characterization
DRUG PRODUCT
Formulation Development
Manufacturing & Analytical Method
NONCLINICAL STUDIES
PHARMACOLOGY
Mechanism of Action
Efficacy
PHARMACOKINETICS
ADME-Tox Studies
Bioanalytical Method Development & Validation
TOXICOLOGY
Dose Formulation Method Development
Acute Toxicity – Rodent & Non-Rodent
Sub-Acute Toxicity – Rodent & Non-Rodent
REGULATORY AFFAIRS
IND Drafting
IND Compilation & Document QC
IND Submission
• Clinical candidate declaration: Oct ‘16
• IND filing: Sept ‘17
32. Business Development Efforts for COTI-2, COTI-219 & ROSALIND
32
Pharma partners in discussion for COTI-2 licensing deals in the US
Pharma partners in discussion for COTI-2 development and ex-US licensing deals
Recent Pharma Partners inbound interest in COTI-219 (both in combination with
COTI-2 and solo; US and ex-US interest)
Cancer centers for academic collaborations, including institutional or government
support for pre-clinical and clinical studies (combination), grant opportunities
ROSALIND: Bioinformatics groups, oncologists directly or via patient request
33. Strengthen the Balance Sheet to Execute on Strategy
• Current cash position: ~$5MM
• Cash runway: ~April 2017
• Opportunities for funding and possible corporate re-
positioning:
– Private placement
• Existing shareholder base
• US potential investors
– Institutional investors
– Partnership activities
• COTI-2 ex-US
• COTI-219 US or ex-US
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34. LFS Orphan Drug Application
• Office of Orphan Products Development (OOPD) designates products for
the treatment of cancer by tumor type
• If COTI wishes to receive designation for the use of COTI-2 in the
treatment of a cancer that is related to the p53 mutation, submit a
request for each of these tumor types separately
• Path forward:
– COTI drafted resubmission for rhabdomyosarcoma
– Recent KOL meetings have recommended all comers in soft tissue
sarcoma as rhabdo patients typically are successful after receiving first
line treatment
– COTI assessing clinical trial design against orphan drug application
– Resolution expected in fourth quarter 2016
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35. Communications and Investor Outreach
• Communications Outreach (previous 6 months at-a-glance):
– Release regular news flow announcing progress and key events (16 press releases)
– Post strategic and informative blog articles (12 blog posts with 34,381 page
views/6,048 unique readers)
– Distribute email updates to keep the community informed on company progress (19
reports to 273 subscribers)
– Publish peer reviewed publications (Oncotarget, May '16)
– Enhance visibility and profile with 3rd party coverage (11 articles)
– Increase social media outreach (COTI Twitter 3,181 followers; COTI Facebook 1,379
followers; ROSALIND Twitter 3,200 followers; ROSALIND Facebook 160 followers;
SharePitch Twitter 17,500 followers; SlideShare 68,000+ views)
• Investor Visibility:
– Obtain additional analyst coverage (Zack’s)
– Establish routine updates to the investment community (management calls/visits)
– Refine approach to IR (new firm combined with internal management)
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36. 36
Management Team Directors
Wayne Danter, MD, FRCPC
• Co-founder, CEO & CSO
• Former Associate Professor of Medicine at
Western University
Alison Silva, MSc
• President
• Co-founder, former EVP & COO, Synlogic
• Co-founder & Principal, The Orphan Group
Gene Kelly
• Chief Financial Officer
• Former VP Finance, Cuddy Farms
Kowthar Salim, PhD, MBA
• Program Director and Senior Scientist
John Drake, LLB, Chairman
• Chairman, Whippoorwill Holdings Limited
Wayne Danter, MD, FRCPC, CEO
Alison Silva, MSc, President
Douglas Alexander, CPA, CA
• Chairman, Hydrogenics Corporation
Bruno Maruzzo, MASc, MBA
• President, TechnoVenture Inc.
Dave Sanderson, LLB
• President & CEO, KFL Investment Management
Inc.
John Yoo, MD FRCPC
• Professor, Chairman and City-wide Chief of
Otolaryngology – Head and Neck Surgery at
Western University
Bharatt Chowrira, PhD, JD
• President, Synlogic
Committed Leadership
37. 37
Dr. Gordon Mills from the University of Texas MD Anderson Cancer Center,
Houston, TX, Chairman
Dr. Douglas Levine from the Memorial Sloan-Kettering Cancer Center, New York
City, NY
Dr. David Parkinson from New Enterprise Associates, Menlo Park, CA
Dr. Marshall Strome from the Center for Head and Neck Oncology at Roosevelt
St. Luke's Hospital, New York City, NY
Dr. Nancy Chang, President, Apex Enterprises, Inc, and adjunct professor at the
Departments of Medicine and Genetics at Baylor College of Medicine, Houston,
TX
………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………..
Dr. Wayne R. Danter, Chief Scientific Officer, Critical Outcome Technologies Inc,
London, ON
Scientific Advisory Board