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Sumith Kularatne

On Target Laboratories focuses on developing small molecule drugs that target and illuminate specific cancerous and diseased cells, avoiding healthy tissues. It is led by Dr. Sumith Kularatne, who has over 25 patents and has advanced 6 drug candidates into human clinical trials. The company's lead candidate, OTL38, has been shown safe in phase I trials and effective in phase II trials for ovarian cancer, with upcoming phase II trials for lung cancer. OTL38 and other candidates use targeted drug delivery with ligands to illuminate and treat diseases precisely while minimizing side effects.

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On Target Laboratories focuses on the discovery and development of small molecules that target and illuminate specific cancerous cells and other diseased tissue. It is pioneering novel techniques that could substantially impact patient outcomes Pinpointing diseased cells, avoiding healthy tissues CANCER IS ONE of the leading causes of death worldwide. Smoking, lack of exercise and poor diet, in addition to an ageing population, have led to an increased burden of cancer, particularly in developed countries where incidence increases annually. There are a range of treatments available to cancer patients, with the most suitable for each individual depending on a large variety of factors. However, the majority of cancer therapies today involve treatment with cytotoxic drugs; although this can be an effective method, these drugs are distributed indiscriminately into the body, damaging both diseased and healthy cells thereby leading to severe side effects. COAXING BIOMARKERS OVEREXPRESSION Thus, it is crucial that researchers work on developing new and improved methods for treating cancer. Dr Sumith Kularatne has devoted much of his work to achieving novel therapeutic modalities for cancer. Using ligands, such as antibodies or small molecules, we can deliver imaging and therapeutic agents to diseased cells, he explains. It will allow avoiding collateral damage to healthy cells while affecting diseased cells. As the Vice President of Research and Development at On Target Laboratories (OTL) in West Lafayette, USA, Sumiths scientific Could you begin by telling us a bit about your history and what drives you? I grew up in Sri Lanka, where I had limited access to science and technology, among many other things. I was a chemistry honour student in my college. Certain disappointments fashioned my thinking into being more industrious, creative and innovative, and taught me to persevere. They also helped strengthen my work ethic, pushing me to accomplish greater things. As a result I have been fortunate to work with great scientists such as Philp Low, PhD at Purdue University, West Lafayette, Indiana, and Peter Schultz, PhD at The Scripps Research Institute (TSRI), San Diego, California, to conduct cutting-edge science on drugdesign. What was it that led to your research into drug design and development? My grandfather died from cancer when I was very young, so I never got the opportunity to know him. My memory of him is composed of second-hand accounts of those who knew him. I often thought if I got the chance I would work on cancer drugs so that other children would get enough time to spend with their loved ones. I had a passion for organic chemistry, and it was so evident from the earlier stage of my college years that it is my niche area. It fascinates me to design drugs. As a pioneer in your field, what is your proudest achievement to date? Although many of the drugs I have developed have gone to human clinical trials and I have collected several accolades for my work I feel the proudest moment of my career is the first two drugs that I designed and developed for prostate cancer. They are currently in human clinical trials for prostate cancer; it makes me feel very humbled and extremely fortunate. How important is collaboration to you? I consider it very important. I want to emphasise that all the accomplishments I have been involved with were a team effort. I have always been around a great group of people committed to work in cohesion with one another. I have been guided by great leaders and mentors. I have great parents, family and friends who support meunconditionally. Finally, what are your plans for the next five to 10 years? Drug design is my passion and I want to keep doing what I am good at and be engaged in a line of work I thoroughly enjoy. Dr Sumith Kularatne is a pioneer in designing and developing methods for treating cancer and inflammatory diseases. He discusses his work with ligand-targeted drug delivery, his inspirations and proudest moments to date Dramatically improving lives with targeted delivery INTERNATIONAL INNOVATION CANCER
ON TARGET LABORATORIES OBJECTIVE To develop new inventions that will pave the way to ensure a better future for people with cancer or a better future for the next generation. KEY RESEARCH ARTICLES A CXCR4-targeted site-specific antibody-drug conjugate Recruiting cytotoxic T cells to folate-receptor-positive cancer cells. Synthesis and biological analysis of prostate-specific membrane antigen-targeted anticancer prodrugs Prostate-specific membrane antigen targeted imaging and therapy of prostate cancer using a PSMA inhibitor as a homing ligand. Folate-targeted therapeutic and imaging agents for cancer. Quantitation of circulating tumor cells in blood samples from ovarian and prostate cancer patients using tumor-specific fluorescent ligands. Comparative analysis of folate derived PET imaging agents with [(18)F]-2-fluoro-2-deoxy-d-glucose using a rodent inflammatory paw model. Synthesis and composition of amino acid linking groups conjugated to compounds used for the targeted imaging of tumors FUNDING Two privately funded organisations (J Tomas Hurvis, Chicago, IL and Christian Pension Fund at Indianapolis,IN) National Institutes of Health (NIH) SBIR grant awards Indiana PTAC Office of Small Business and Entrepreneurship CONTACT Dr Sumith Kularatne Vice President of Research and Development On Target Laboratories (OTL) 1281 Win Hentschel Blvd West Lafayette Indiana, 47906 USA T +1 765 588 4547 E skularatne@ontargetlabs.com www.researchgate.net/profile/Sumith_Kularatne http://bit.ly/1Q4Ji8V https://twitter.com/SumithKularatne http://bit.ly/GooglePlusSumith http://bit.ly/FacebookSumith OTL specialises in developing novel optical imaging agents that target and illuminate pathological cells. The technology provides surgeons with a precise lighted road map to effectively diagnose and surgically treat diseased tissue ranging from cancer to inflammatory diseases. To date OTL has received $25 million of private funding. OTL38, OTLs lead development candidate, has been proven safe in a recent phase I trial and effective in a completed phase II clinical trial for ovarian cancer. A phase II trial will begin in lung cancer patients this summer. Commercialisation of OTL38 for ovarian and lung cancer patients is scheduled for early 2018 and 2020 respectively. A phase I clinical trial of OTL78 for prostate cancer will be starting in 2017. ADDITIONAL HIGHLIGHTS OF DR KULARATNES WORK PSMA-targeted radioimaging agent (Purdue/Endocyte, USA), evaluated in a phase I clinical trials at IU medical school, USA PSMA-targeted fluorescence imaging agent, successfully quantified circulating tumour cells from prostate cancer patients blood samples (Purdue Cancer Centre) PSMA-targeted chemotherapeutic agent (Purdue/Endocyte, USA), evaluated in a phase I clinical trial at MD Anderson, USA CXCR4-targeted antibody drug conjugate (TSRI, USA), preclinical development at Ambrx, USA Folate-antiCD3 Fab (immunotherapy/ antibody-dependent cell-mediated cytotoxicity) to redirect T cells to cancer cells (TSRI, USA) Preclinical development at Ambrx, USA FR-targeted PET imaging agent (Purdue/Merck Research laboratories, USA/VU Medical Centre, Amsterdam). Development of OTL38 (concept to clinical candidate) accomplished in three months, OTL, USA efforts have resulted in six drug candidates in human clinical trials with multiple companies. Currently, he has over 25 issued/pending patents worldwide and continues to make pioneering contributions to the treatment of cancer and inflammatory diseases. AN OVERWHELMING CASE FOR LIGANDS The benefits of using ligand-targeted drug delivery are numerous and could have a tremendous impact on peoples lives. In addition to producing a higher signal-to- background ratio, Sumith and his team have found that targeted drugs have higher efficacy and minimal toxicity, especially when the ligand targets a receptor that is overexpressed on the diseased cell and internalises the drug via receptor-mediated endocytosis. There are additional benefits: We can use the same ligand to deliver imaging and/or therapeutic agents, explains Sumith. We can therefore select the correct patient population, namely those that express the biomarker using the imaging agent, and then treat those patients with the ligand-therapeutic conjugate. The ligand-imaging agent conjugate can even be used to monitor the response to the therapy, enabling the researchers to determine itsefficacy. PAVING A PATH TO BETTER FUTURES It is no coincidence that OTL is succeeding in its mission to improve the efficacy of treatments for cancer, as Sumith has consistently demonstrated his passion and knack for drug design. Under his guidance, OTL has developed a strong pipeline for several types of cancer and inflammatory diseases. OTL38, a folate receptor (FR)-targeted near infrared (NIR) dye, has been proven safe in a phase I trial and effective in a completed phase II clinical trial for ovarian cancer. A phase II trial for lung cancer will begin this summer. The same proprietary NIR dye has been conjugated to additional ligands targeting receptors on prostate (OTL78: PSMA-targeted NIR agent), colon (OTL338: CA-IX-targeted NIR agent), and pancreatic (OTL81: CCK2R-Targeted NIR agent) cancers. These same ligands can also be conjugated to a photodynamic therapeutic (PDT) agent, giving surgeons the option to visualise and burn targeted lesions using the same light source and camera. A lead folate- PDT compound (OTL228) has been identified with others to follow. Sumiths groundbreaking work is a by-product of his yearning to do something that makes an impact on peoples lives a motivation that is to be admired. I view new data or new technologies coming out from fellow scientists with a positive attitude and integrating them enables me to discover better therapies with higher efficacy, he enthuses. I hope to pave the way to ensure a better future for people suffering from cancer and for the children of next generations. www.internationalinnovation.com

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  • 1. On Target Laboratories focuses on the discovery and development of small molecules that target and illuminate specific cancerous cells and other diseased tissue. It is pioneering novel techniques that could substantially impact patient outcomes Pinpointing diseased cells, avoiding healthy tissues CANCER IS ONE of the leading causes of death worldwide. Smoking, lack of exercise and poor diet, in addition to an ageing population, have led to an increased burden of cancer, particularly in developed countries where incidence increases annually. There are a range of treatments available to cancer patients, with the most suitable for each individual depending on a large variety of factors. However, the majority of cancer therapies today involve treatment with cytotoxic drugs; although this can be an effective method, these drugs are distributed indiscriminately into the body, damaging both diseased and healthy cells thereby leading to severe side effects. COAXING BIOMARKERS OVEREXPRESSION Thus, it is crucial that researchers work on developing new and improved methods for treating cancer. Dr Sumith Kularatne has devoted much of his work to achieving novel therapeutic modalities for cancer. Using ligands, such as antibodies or small molecules, we can deliver imaging and therapeutic agents to diseased cells, he explains. It will allow avoiding collateral damage to healthy cells while affecting diseased cells. As the Vice President of Research and Development at On Target Laboratories (OTL) in West Lafayette, USA, Sumiths scientific Could you begin by telling us a bit about your history and what drives you? I grew up in Sri Lanka, where I had limited access to science and technology, among many other things. I was a chemistry honour student in my college. Certain disappointments fashioned my thinking into being more industrious, creative and innovative, and taught me to persevere. They also helped strengthen my work ethic, pushing me to accomplish greater things. As a result I have been fortunate to work with great scientists such as Philp Low, PhD at Purdue University, West Lafayette, Indiana, and Peter Schultz, PhD at The Scripps Research Institute (TSRI), San Diego, California, to conduct cutting-edge science on drugdesign. What was it that led to your research into drug design and development? My grandfather died from cancer when I was very young, so I never got the opportunity to know him. My memory of him is composed of second-hand accounts of those who knew him. I often thought if I got the chance I would work on cancer drugs so that other children would get enough time to spend with their loved ones. I had a passion for organic chemistry, and it was so evident from the earlier stage of my college years that it is my niche area. It fascinates me to design drugs. As a pioneer in your field, what is your proudest achievement to date? Although many of the drugs I have developed have gone to human clinical trials and I have collected several accolades for my work I feel the proudest moment of my career is the first two drugs that I designed and developed for prostate cancer. They are currently in human clinical trials for prostate cancer; it makes me feel very humbled and extremely fortunate. How important is collaboration to you? I consider it very important. I want to emphasise that all the accomplishments I have been involved with were a team effort. I have always been around a great group of people committed to work in cohesion with one another. I have been guided by great leaders and mentors. I have great parents, family and friends who support meunconditionally. Finally, what are your plans for the next five to 10 years? Drug design is my passion and I want to keep doing what I am good at and be engaged in a line of work I thoroughly enjoy. Dr Sumith Kularatne is a pioneer in designing and developing methods for treating cancer and inflammatory diseases. He discusses his work with ligand-targeted drug delivery, his inspirations and proudest moments to date Dramatically improving lives with targeted delivery INTERNATIONAL INNOVATION CANCER
  • 2. ON TARGET LABORATORIES OBJECTIVE To develop new inventions that will pave the way to ensure a better future for people with cancer or a better future for the next generation. KEY RESEARCH ARTICLES A CXCR4-targeted site-specific antibody-drug conjugate Recruiting cytotoxic T cells to folate-receptor-positive cancer cells. Synthesis and biological analysis of prostate-specific membrane antigen-targeted anticancer prodrugs Prostate-specific membrane antigen targeted imaging and therapy of prostate cancer using a PSMA inhibitor as a homing ligand. Folate-targeted therapeutic and imaging agents for cancer. Quantitation of circulating tumor cells in blood samples from ovarian and prostate cancer patients using tumor-specific fluorescent ligands. Comparative analysis of folate derived PET imaging agents with [(18)F]-2-fluoro-2-deoxy-d-glucose using a rodent inflammatory paw model. Synthesis and composition of amino acid linking groups conjugated to compounds used for the targeted imaging of tumors FUNDING Two privately funded organisations (J Tomas Hurvis, Chicago, IL and Christian Pension Fund at Indianapolis,IN) National Institutes of Health (NIH) SBIR grant awards Indiana PTAC Office of Small Business and Entrepreneurship CONTACT Dr Sumith Kularatne Vice President of Research and Development On Target Laboratories (OTL) 1281 Win Hentschel Blvd West Lafayette Indiana, 47906 USA T +1 765 588 4547 E skularatne@ontargetlabs.com www.researchgate.net/profile/Sumith_Kularatne http://bit.ly/1Q4Ji8V https://twitter.com/SumithKularatne http://bit.ly/GooglePlusSumith http://bit.ly/FacebookSumith OTL specialises in developing novel optical imaging agents that target and illuminate pathological cells. The technology provides surgeons with a precise lighted road map to effectively diagnose and surgically treat diseased tissue ranging from cancer to inflammatory diseases. To date OTL has received $25 million of private funding. OTL38, OTLs lead development candidate, has been proven safe in a recent phase I trial and effective in a completed phase II clinical trial for ovarian cancer. A phase II trial will begin in lung cancer patients this summer. Commercialisation of OTL38 for ovarian and lung cancer patients is scheduled for early 2018 and 2020 respectively. A phase I clinical trial of OTL78 for prostate cancer will be starting in 2017. ADDITIONAL HIGHLIGHTS OF DR KULARATNES WORK PSMA-targeted radioimaging agent (Purdue/Endocyte, USA), evaluated in a phase I clinical trials at IU medical school, USA PSMA-targeted fluorescence imaging agent, successfully quantified circulating tumour cells from prostate cancer patients blood samples (Purdue Cancer Centre) PSMA-targeted chemotherapeutic agent (Purdue/Endocyte, USA), evaluated in a phase I clinical trial at MD Anderson, USA CXCR4-targeted antibody drug conjugate (TSRI, USA), preclinical development at Ambrx, USA Folate-antiCD3 Fab (immunotherapy/ antibody-dependent cell-mediated cytotoxicity) to redirect T cells to cancer cells (TSRI, USA) Preclinical development at Ambrx, USA FR-targeted PET imaging agent (Purdue/Merck Research laboratories, USA/VU Medical Centre, Amsterdam). Development of OTL38 (concept to clinical candidate) accomplished in three months, OTL, USA efforts have resulted in six drug candidates in human clinical trials with multiple companies. Currently, he has over 25 issued/pending patents worldwide and continues to make pioneering contributions to the treatment of cancer and inflammatory diseases. AN OVERWHELMING CASE FOR LIGANDS The benefits of using ligand-targeted drug delivery are numerous and could have a tremendous impact on peoples lives. In addition to producing a higher signal-to- background ratio, Sumith and his team have found that targeted drugs have higher efficacy and minimal toxicity, especially when the ligand targets a receptor that is overexpressed on the diseased cell and internalises the drug via receptor-mediated endocytosis. There are additional benefits: We can use the same ligand to deliver imaging and/or therapeutic agents, explains Sumith. We can therefore select the correct patient population, namely those that express the biomarker using the imaging agent, and then treat those patients with the ligand-therapeutic conjugate. The ligand-imaging agent conjugate can even be used to monitor the response to the therapy, enabling the researchers to determine itsefficacy. PAVING A PATH TO BETTER FUTURES It is no coincidence that OTL is succeeding in its mission to improve the efficacy of treatments for cancer, as Sumith has consistently demonstrated his passion and knack for drug design. Under his guidance, OTL has developed a strong pipeline for several types of cancer and inflammatory diseases. OTL38, a folate receptor (FR)-targeted near infrared (NIR) dye, has been proven safe in a phase I trial and effective in a completed phase II clinical trial for ovarian cancer. A phase II trial for lung cancer will begin this summer. The same proprietary NIR dye has been conjugated to additional ligands targeting receptors on prostate (OTL78: PSMA-targeted NIR agent), colon (OTL338: CA-IX-targeted NIR agent), and pancreatic (OTL81: CCK2R-Targeted NIR agent) cancers. These same ligands can also be conjugated to a photodynamic therapeutic (PDT) agent, giving surgeons the option to visualise and burn targeted lesions using the same light source and camera. A lead folate- PDT compound (OTL228) has been identified with others to follow. Sumiths groundbreaking work is a by-product of his yearning to do something that makes an impact on peoples lives a motivation that is to be admired. I view new data or new technologies coming out from fellow scientists with a positive attitude and integrating them enables me to discover better therapies with higher efficacy, he enthuses. I hope to pave the way to ensure a better future for people suffering from cancer and for the children of next generations. www.internationalinnovation.com