If you were not able to make it out to the conference today, we have also made a few of our new marketing materials from the conference available below.
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We're at the 2017 Cantech Investment Conference at the Metro Toronto Convention Centre in Toronto today. If you are attending the conference, please be sure to visit us at Booth #512, or drop by the Mackie Stage at 3:10 p.m. as our President and CEO, Alison Silva presents a general overview of the Company and our initial focus on targeted therapies for the treatment of multiple cancers and other unmet medical needs.
If you were not able to make it out to the conference today, we have also made a few of our new marketing materials from the conference available below.
Critical Outcome to be a Panelist and Featured Presenter at Cantech Investment Conference in Toronto
We are pleased to announce that Critical Outcome will be a panelist and a featured presenter at the 2017 Cantech Investment Conference on January 18, 2017, at the Metro Toronto Convention Centre in Toronto.
Our President and CEO, Alison Silva, will participate in a panel discussion entitled “Undervalued Emerging Biotech Companies Developing Breakthrough Therapies” at 12:00 p.m. on the Mackie Stage. The panel discussion involving biotech executives will be moderated by Mr. Eden Rahim of Next Edge Capital Corp.
At 3:10 p.m., also on the Mackie Stage, Ms. Silva will present a general overview of the Company and its initial focus on targeted therapies for the treatment of multiple cancers and other unmet medical needs.
The slide presentation will be available on the Company's website and on SlideShare at www.slideshare.net/CriticalOutcome following the live presentation.
If you are going to be at the conference, please be sure to visit us at Booth #512.
Earlier this week during the JP Morgan Healthcare and Biotech Showcase conferences, our President and CEO, Alison Silva, hosted a panel discussion with some leading industry veterans and patient advocates: Henri Termeer, former Chairman and CEO of Genzyme, Phil Vickers, Head of R&D at Shire, Flemming Ornskov, CEO of Shire, and Debra Miller, co-founder and CEO of CureDuchenne. The topic was “Unmet Needs, Uncommon Commitment: The Shift Toward Investment in Rare Diseases”. Panelists held an engaging discussion about how the approach to rare disease research, drug development, commercialization and investment have changed in recent years.
This event provided great exposure for COTI and was a topic dear to our hearts given our current focus on rare diseases.
“We are pleased to report that the first two patients in cohort 4 have begun receiving COTI‐2 at a dosage level of 1.7 mg/kg, an increase from the 1.0 mg/kg level of cohort 3. We are further pleased to report that there were no significant adverse events attributed to treatment in any of the cohort 3 patients. Preliminary clinical data is consistent with the low toxicity profile observed during preclinical studies. Accordingly, the independent Dose Escalation Committee granted a favourable opinion to move ahead with the fourth cohort of patients. We are pleased with the Committee’s recommendation and trial advancement to date.” - Alison Silva, President and CEO.
More information about COTI‐2 and the ongoing clinical study is available on our website at: http://criticaloutcome.com/coti‐2.
On Tuesday we announced that our next clinical candidate will be COTI-219. Discovered by our proprietary drug discovery technology platform, CHEMSAS, COTI-219 is a novel oral small molecule compound targeting the mutant forms of KRAS. We thought it might be helpful for our readers to provide more of an overview on the KRAS gene and its mutations.
The KRAS gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous.
The KRAS gene provides your body with instructions for making a protein called K-Ras, which plays a central role in the signaling of a number of cellular pathways that regulate cell growth and proliferation. The K-Ras protein is a GTPase, which means it converts a molecule called guanosine triphosphate (GTP) into another molecule called guanosine diphosphate (GDP). Like a switch, the K-Ras protein is turned on and off by these GTP and GDP molecules. To transmit signals, the K-Ras protein must be turned on by binding to a molecule of GTP. The K-Ras protein is turned off (inactivated) when it converts the GTP to GDP. When the protein is bound to GDP, it does not relay signals to the cell's nucleus.
While most mutations in genes are expected to cause their inactivation, with KRAS genes the opposite occurs - they become more active in signalling. With KRAS mutations, the GTPase is inactivated, meaning that GTP continues to engage the switch, and the Ras signalling function is unable to be turned "off".
KRAS mutations are found in many human cancers, with the highest prevalence in pancreatic adenocarcinomas (90%), colorectal cancers (45%) and lung cancers (35%). KRAS mutations are also predictive of a very poor response to colorectal cancer therapies, such as panitumumab and cetuximab. Targeted therapies that can block the function of mutant KRAS protein, but not the wild type KRAS, would be transformative in the successful treatment of a large number of cancer indications.
“KRAS mutations occur in a large number of cancers and represent a tremendous unmet clinical need, making for a highly desirable drug target. These mutations are detected in up to one‐fourth of all human cancers, particularly lung, colorectal, pancreatic, and thyroid. Selectively targeting the mutant forms of KRAS without inhibiting wild type KRAS function has been the focus of intense research for over two decades, with limited success. It is therefore very exciting that COTI‐219, which is designed to be selective against the mutant form of KRAS, is shown to be efficacious in multiple pre‐clinical tumor model systems." - Alison Silva, President of Critical Outcome Technologies Inc.
Ovarian cancer occurs when cells in one or both of a woman's ovaries begin to grow out of control. The ovaries are two small glands, located on either side of your uterus. They produce female sex hormones and store and release eggs (ova).
Treatments for ovarian cancer are more successful when the cancer is found early. Unfortunately, the cancer has usually already spread by the time it is found. To continue to help raise awareness, here are five things every woman should know about ovarian cancer:
Learn about our clinical stage compound targeting ovarian and other gynecological cancers by visiting our website at www.criticaloutcome.com/coti-2.
Both germ cell and sex-cord stromal cell ovarian cancers respond well to treatment and are often curable.
Why we need more awareness?
Why we need better treatment options?
Ovarian cancer is treated with one or a combination of treatments, most commonly surgery and chemotherapy. Treatment options and recommendations depend on several factors, including the type and stage of cancer, possible side effects, the patient’s preferences and overall health, and personal considerations, such as the woman's age and if she is planning to have children.
When the drugs cisplatin and carboplatin stop working, the cancer is said to be platinum resistant and oncologists currently have no treatment options to offer these patients. New treatments are needed. Our clinical stage small molecule called COTI-2 acts by normalizing the p53 protein function in cancer cells with such mutations. As the vast majority of ovarian cancers have this mutation, it appears that of all the ovarian drugs in development at this time, COTI-2 offers the most exciting treatment opportunity. In fact, we believe that COTI-2 represents a significant therapeutic advantage over treatments currently available for ovarian cancer.
Our lead compound, COTI-2, has a major mechanism of action in human cancer cells that is dependent on p53 gene mutation status. This is important as drug treatment for p53 mutations represents a novel therapy and would be a first-in-class treatment for the drug company bringing COTI-2 to market.
Selective and potent anti-cancer activity
Extensive preclinical studies demonstrated COTI-2’s ability to restore mutant p53 function and thus induce cancer cell death in many common p53 mutations. In those studies, COTI-2 as a single agent either completely halted tumor growth or led to dramatic tumor regression depending on the dose amount and p53 mutation type. Moreover, there was no observable toxicity in those preclinical studies. >> OVCAR-3 xenograft model
Unlike nearly every other cancer treatment in existence today, it appears through our preclinical studies that COTI-2 is non-genotoxic. Conventional chemotherapy involves the killing of all growing and dividing cells in the body (cancer or otherwise), which often leads to significant toxic side effects in patients. By contrast, COTI-2 specifically targets and primarily destroys tumor cells.
We commenced our Phase 1 clinical trial of COTI‐2 at the end of 2015, with COTI-2 initially being evaluated for the treatment of gynecologic cancers (including ovarian cancer). The Phase 1 clinical trial is being carried out at the MD Anderson Cancer Center at the University of Texas and the Lurie Cancer Center at Northwestern University. Dosing of women in the third cohort of the ongoing clinical trial commenced in July 2016.
Clinical trials of COTI-2 are also planned in the U.S. and Canada for the treatment of patients with recurrent head and neck squamous cell cancer.
Kevetrin, which is being developed by Beverly, Massachusetts-based Cellceutix Corporation, is a small molecule that belongs to a different class of compounds known as thioureals. Kevetrin's mechanism of action revealed the compound's ability to induce cell cycle arrest and apoptosis in a non-genotoxic way in wild type p53 and mutant p53.
A Phase 1 study evaluating Kevetrin in advanced solid tumors commenced in August 2012. Preliminary findings from Cellceutix’s Phase 1 trial showed Kevetrin to be well-tolerated in patients at increasingly higher dosing levels and that the drug activated p53 by inducing p21 expression. Additional efficacy data released earlier in 2016 showed two-thirds of patients, regardless of tumor type, had increases in p21 expression relative to pre-treatment levels, and that this appeared to be both a time-dependent and dose-dependent response among patients.
In February 2016, Cellceutix concluded its Phase 1 trial in solid tumors and is now moving Kevetrin into mid-stage trials, including, in the near-term, ovarian cancer. Other Phase 2 trials are planned for pancreatic cancer, acute myelogenous leukemia (AML), retinoblastoma and renal cell carcinoma.
In comparison, COTI-2 has a big advantage in terms of efficacy. Based on preclinical experiments, COTI-2 is the more potent activator of mutant p53 with IC50s (a measure of the effectiveness of a substance in inhibiting a specific biological or biochemical function, with lower being better) in the low nanomolar range in multiple human cancer cell lines, whereas Kevetrin is active at greater than 100 micromolar level.
Another p53-focused company is privately held Aprea AB, based out of Stockholm, Sweden. Aprea AB’s lead compound, Aprea-246, also activates mutant p53. Unlike COTI-2, Aprea-246 functions in a more limited way by inducing wild type conformation in a smaller number of p53 mutations. Additionally, APR- 246 is active only at a high micromolar range. Aprea 246 would be the most like COTI-2 of these two compounds.
The main differences between these three drugs are: (1) potency – COTI-2 is effective at nanomolar concentrations, (2) COTI-2 is effective against a wider range of p53 mutations and (3) COTI-2 is given orally not intravenously.
Drugs like COTI-2 have the potential to revolutionize outpatient cancer therapy. COTI-2’s specific protein target, low toxicity, combination effectiveness with standard agents and potential for longer term outpatient therapy as an oral agent support a dramatic change in the treatment of susceptible cancers.
Ask COTI: How does your drug discovery process using CHEMSAS® differ from the traditional drug discovery process?
The traditional drug discovery process is a slow and labor-intensive process carried out mostly in the wet lab. This process can last as long as five years and cost more than $200 Million – and if successful, a drug candidate then enters the long and even more expensive process of clinical trials in hopes of an eventual FDA approval.
Our process is radically different and uses CHEMSAS – our proprietary drug discovery platform technology based upon a hybrid of machine learning technologies and proprietary algorithms. CHEMSAS utilizes a series of predictive computer models to identify compounds with a high probability of being successfully developed from disease specific drug discovery through chemical optimization and preclinical testing. In other words, much of the discovery work is performed in computer simulations, which is very cost-effective in terms of identifying high probability drug candidates that we want to move forward with.
Compared to the traditional drug discovery process, our process is much more efficient. Since much of our process is initially performed in computer simulations, we are able to develop candidates very quickly. With CHEMSAS we can essentially go from a concept of a molecule that we wish to develop, to a point where we’re able to synthesize and begin testing that molecule in approximately three months. This faster time to market saves millions of dollars for drug discovery and development and yields increased profits for each successful new drug by providing a longer revenue period under the patent life.
To make a long story short, CHEMSAS dramatically reduces the time and cost of the drug discovery process. Moreover, our largely computerized process has already identified a number of extremely promising drug candidate molecules.
We are delighted to announce the opening of our U.S. headquarters in Boston, Massachusetts. The new office space is located at 127 Main Street, in close proximity to the plethora of life science companies and teaching hospitals in the area.
The opening of our Boston office again affirms our commitment to enhance the value of our Company by improving our visibility and exposure in the U.S. market. Management believes the Company has reached an important inflection point in its growth that requires the Company to open itself up to the larger, and more life science‐focused, U.S. market
“I’m thrilled to be heading up our Boston office and spearheading several key functions out of this site, including public and investor relations, corporate and business development and clinical operations. The Boston area is the leading biotechnology and life sciences hub in the world and offers innovative biotech companies such as ours access to world-class talent, investors and collaboration partners.” - Alison Silva, President.
“Gaining a foothold in the U.S. has been a strategic objective of ours and part of my vision for the Company. Obtaining our listing on the OTCQB back in June of 2014 to enable investments from American investors, was the first step to improving our visibility and exposure in the U.S. Since then we have been introduced to, and established relationships with, many industry leaders and life sciences investors. I believe that with the opening of our Boston office we are very well poised to build and expand these relationships as we rapidly advance our clinical programs.” – Dr. Wayne Danter, Chief Executive Officer.
The Boston area is a leading region for life sciences and life science companies. The area offers a large variety of amenities and services, not the least of which are connections to the region’s intellectual talent and life sciences investors. In fact, the density of pharmaceutical companies, world-class research institutions, biotech start-ups, world-class educational facilities, clinical collaborations and life sciences investors make Boston a pretty special and unique place. The Boston area boasts approximately 30,000 scientists and other workers involved in biotech, pharmaceutical and clinical research. This is the highest concentration of life-science research workers in the U.S., according to U.S. Bureau of Labor statistics provided by the Massachusetts Biotechnology Council.
On June 16, 2014, the Company commenced trading in the United States on the OTC Markets OTCQB trading platform for venture companies under the symbol COTQF. The OTCQB platform has enabled U.S.‐based investors to obtain information about the Company and invest through a trading platform familiar to them.
Welcome to our blog. We use this space to provide more insight into the latest developments in our business as well as recent events in the field of drug discovery and development.