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2ST20 On Target 21253_Final 8-15-16

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Sumith Kularatne

On Target Laboratories (OTL) is developing novel optical imaging agents that target and illuminate cancerous cells. OTL's lead candidate, OTL38, is a near-infrared dye conjugated to a ligand that targets folate receptors, which are overexpressed in several types of cancer. OTL38 has undergone successful preclinical testing and a phase I clinical trial. Additional candidates target prostate-specific membrane antigen and receptors for ovarian, lung, renal, colon, liver, breast, head and neck, and pancreatic cancers. OTL's technology provides surgeons with real-time visualization of cancerous tissues during surgery to more precisely and completely remove tumors.

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FUTURE OF ONCOLOGY Pan European Networks: Science & Technology 20 www.paneuropeannetworks.com1 PROFILE S urgical removal of malignant disease constitutes one of the most common and effective therapeutic modalities for most solid tumours.There is enough literature evidence to show that resection of all detectable malignant lesions has a significant impact on patient outcomes and may extend life expectancy or reduce morbidity.Therefore, it is important to identify all the malignant lesions accurately and completely. However, currently surgeons must rely primarily on their visual and tactile senses, aided at times by static pre-operative images, to excise the tumour tissues. Despite the recognition of the importance of removal of the tumour, many malignant lesions still escape detection, leading to recurrence of the disease and often death. Thus, there is an imperative medical demand for improved tumour identification. Image-guided Image-guided surgery is an emerging technology that aids in the accurate identification and removal of malignant tissues without compromising healthy tissues. However, an inherent challenge in the field is the development of imaging agents that selectively accumulate in the tumour tissues but not in the healthy adjacent tissues.Therefore, tumour-targeted near-infrared (NIR) dyes are getting increased attention because of their ability to increase sensitivity and specificity to resect tumours during image-guided surgery. OTL is targeting NIR dyes to receptors/biomarkers that are over-expressed on cancer cells by conjugating to a tumour-specific targeting ligand via a suitable spacer.This ligand-targeted drug delivery technology is based on the pioneering work of Philip S Low, PhD,the Ralph C Corley Distinguished Professor of Chemistry at Purdue University and director of the Purdue University Center for Drug Discovery. Examples of tumour targeting ligands that are developed under Dr Lows guidance include folic acid, which exhibits specificity for folate receptor alpha (FR留)-expressing cancers positive cancers of the ovary, kidney, lung, endometrium, breast, and colon, olate receptor beta (FR硫)-expressing tumour-associated macrophages and myeloid-derived suppressor cells (MDSCs) and DUPA,which can deliver attached fluorescent dyes selectively to cells expressing prostate-specific membrane antigens (PSMA), i.e. prostate cancers and the neovasculature of other solid tumours. Lighted roadmap OTL technology provides surgeons a precise lighted road map to more effectively and efficiently diagnose and surgically treat diseased tissue ranging from cancer to autoimmune and inflammatory diseases. On Targets lead development candidate is OTL38, a modular probe comprised of a NIR dye conjugated to a ligand (that mimic folic acid) via a spacer that play significant roles as: 1) a part of targeting ligand to improve the binding affinity and specificity for folate receptor; and 2) a part of the NIR dye that enhances the fluorescence intensity (brightness) with unique wave length. OTL38 has a very high affinity and specificity to both FR留 and FR硫, highly stable during synthesis and storage, demonstrates ease of synthesis in small scale to GMP manufacturing, and is highly specific for FR-positive cancer cells in culture and in animal models for both primary and metastatic cancer cells, with no toxicity in rats and dogs. Based on these successful preclinical data, OTL38 entered into a Phase 1a clinical trial in Leiden, the Netherlands, in January 2014. OTL38 has been proven safe in a recent phase I trial and effective in a completed phase II clinical trial for the treatment of ovarian On Target Laboratories (OTL) is specialising in developing novel optical imaging agents that target and illuminate pathological cells Dr Sumith Kularatne
www.paneuropeannetworks.com Pan European Networks: Science & Technology 20 2 PROFILE Dr Sumith Kularatne Vice-President of Research and Development On Target Laboratories (OTL), USA +1 765 588 4547 skularatne@ontargetlabs.com Tweet @SumithKularatne www.researchgate.net/profile/Sumith_Kularatne http://bit.ly/1Q4Ji8V http://bit.ly/GooglePlusSumith http://bit.ly/FacebookSumith cancer.A phase III clinical trial in ovarian cancer and a phase II clinical trial in lung cancer patients will be started in autumn 2016. Commercialisation of OTL38 for ovarian and lung cancer patients is scheduled for early 2018 and 2020 respectively. The same proprietary NIR dye has been conjugated to a PSMA-targeting ligand (DUPA) via a linker that enhances the binding affinity and pharmacokinetic (PK) properties of the final clinical candidate named OTL78.A phase II clinical trial for OTL78 in prostate cancer will began in spring 2017.Additional NIR conjugates such as carbonic anhydrase IX (CA IX)-targeted NIR agent (OTL338), gamma-glutamyl transpeptidase (GGT)-targeted NIR agent (OTL528), and cholecystokinin 2 receptor (CCK2R)-targeted NIR agent (OTL81) are under clinical development for renal, colon, liver, breast, lung, head and neck and pancreatic cancers.Within five years, OTL will have a solution for imaging most, if not all, solid tumours.These same ligands can also be conjugated to a photodynamic therapeutic (PDT) agent giving surgeons the option to burn targeted lesions as well as visualise them using the same light source and camera.A lead folate-PDT compound (OTL228) has been identified with others to follow. Using OTLs revolutionary fluorescent optical imaging technology, patients are injected with the appropriate probe two hours prior to surgery.During surgery an NIR camera system illuminates the labelled cells,displaying their precise location on a flat screen monitor directly adjacent to the patient.Most camera systems can be used for both minimally invasive and open procedures providing physicians and surgeons with the tools to routinely see diseased cells less than a millimetre in size.Improving detection will also improve diagnosis and staging resulting in a more appropriate treatment.Taken together,better surgery and treatment will improve the outcome for a cancer patient.OnTargets surgical imaging technology is expected to become a new standard of care in cancer surgery in the near future. OTL team OTL is led by a well-rounded four member team that each has expertise in different areas that blend well for the companys success. Philip S Low,PhD,is one of the co-founders and chief scientific officer (CSO) of the company. He has published over 350 scientific articles in peer- reviewed journals and holds over 50 US and foreign issued/pending patents. Seven drugs stemming from this research are currently undergoing clinical trials in three companies (Endocyte, On Target Laboratories, and HuLow) that he co-founded. Sumith A Kularatne, PhD, is the vice-president of research and development at OTL. He has pioneer experience in drug designing on both small molecule lignads and antibody-targeted drugs under the guidance of Dr Low at Purdue University,West Lafayette, Indiana, and Peter G Schultz at The Scripps Research Institute, San Diego, California. Sumiths scientific efforts have resulted in six drug candidates in human clinical trials, over 30 US and foreign issued/pending patents and over 30 peer-reviewed publications. Martin R Low,MBA,is the CEO of OTL.He has founded or co-founded seven companies in insurance, renewable energy, consulting, retail and healthcare. He introduced several innovative products that won awards from BusinessWeek,TheThomas Edison Foundation and the Smithsonian Institute.Tim Biro, MBA, is the chief operating officer of OTL. He has entrepreneurial experience in the medical device and pharmaceutical industry serving as the CEO of several companies including SpineMatrix, MORK Process, Therox Pharmaceuticals and OncoImmune. He also has extensive experience in venture capital, as the founder and managing partner of Ohio Innovation Fund, and a partner in Reservoir Venture Partners.

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2ST20 On Target 21253_Final 8-15-16

  • 1. FUTURE OF ONCOLOGY Pan European Networks: Science & Technology 20 www.paneuropeannetworks.com1 PROFILE S urgical removal of malignant disease constitutes one of the most common and effective therapeutic modalities for most solid tumours.There is enough literature evidence to show that resection of all detectable malignant lesions has a significant impact on patient outcomes and may extend life expectancy or reduce morbidity.Therefore, it is important to identify all the malignant lesions accurately and completely. However, currently surgeons must rely primarily on their visual and tactile senses, aided at times by static pre-operative images, to excise the tumour tissues. Despite the recognition of the importance of removal of the tumour, many malignant lesions still escape detection, leading to recurrence of the disease and often death. Thus, there is an imperative medical demand for improved tumour identification. Image-guided Image-guided surgery is an emerging technology that aids in the accurate identification and removal of malignant tissues without compromising healthy tissues. However, an inherent challenge in the field is the development of imaging agents that selectively accumulate in the tumour tissues but not in the healthy adjacent tissues.Therefore, tumour-targeted near-infrared (NIR) dyes are getting increased attention because of their ability to increase sensitivity and specificity to resect tumours during image-guided surgery. OTL is targeting NIR dyes to receptors/biomarkers that are over-expressed on cancer cells by conjugating to a tumour-specific targeting ligand via a suitable spacer.This ligand-targeted drug delivery technology is based on the pioneering work of Philip S Low, PhD,the Ralph C Corley Distinguished Professor of Chemistry at Purdue University and director of the Purdue University Center for Drug Discovery. Examples of tumour targeting ligands that are developed under Dr Lows guidance include folic acid, which exhibits specificity for folate receptor alpha (FR留)-expressing cancers positive cancers of the ovary, kidney, lung, endometrium, breast, and colon, olate receptor beta (FR硫)-expressing tumour-associated macrophages and myeloid-derived suppressor cells (MDSCs) and DUPA,which can deliver attached fluorescent dyes selectively to cells expressing prostate-specific membrane antigens (PSMA), i.e. prostate cancers and the neovasculature of other solid tumours. Lighted roadmap OTL technology provides surgeons a precise lighted road map to more effectively and efficiently diagnose and surgically treat diseased tissue ranging from cancer to autoimmune and inflammatory diseases. On Targets lead development candidate is OTL38, a modular probe comprised of a NIR dye conjugated to a ligand (that mimic folic acid) via a spacer that play significant roles as: 1) a part of targeting ligand to improve the binding affinity and specificity for folate receptor; and 2) a part of the NIR dye that enhances the fluorescence intensity (brightness) with unique wave length. OTL38 has a very high affinity and specificity to both FR留 and FR硫, highly stable during synthesis and storage, demonstrates ease of synthesis in small scale to GMP manufacturing, and is highly specific for FR-positive cancer cells in culture and in animal models for both primary and metastatic cancer cells, with no toxicity in rats and dogs. Based on these successful preclinical data, OTL38 entered into a Phase 1a clinical trial in Leiden, the Netherlands, in January 2014. OTL38 has been proven safe in a recent phase I trial and effective in a completed phase II clinical trial for the treatment of ovarian On Target Laboratories (OTL) is specialising in developing novel optical imaging agents that target and illuminate pathological cells Dr Sumith Kularatne
  • 2. www.paneuropeannetworks.com Pan European Networks: Science & Technology 20 2 PROFILE Dr Sumith Kularatne Vice-President of Research and Development On Target Laboratories (OTL), USA +1 765 588 4547 skularatne@ontargetlabs.com Tweet @SumithKularatne www.researchgate.net/profile/Sumith_Kularatne http://bit.ly/1Q4Ji8V http://bit.ly/GooglePlusSumith http://bit.ly/FacebookSumith cancer.A phase III clinical trial in ovarian cancer and a phase II clinical trial in lung cancer patients will be started in autumn 2016. Commercialisation of OTL38 for ovarian and lung cancer patients is scheduled for early 2018 and 2020 respectively. The same proprietary NIR dye has been conjugated to a PSMA-targeting ligand (DUPA) via a linker that enhances the binding affinity and pharmacokinetic (PK) properties of the final clinical candidate named OTL78.A phase II clinical trial for OTL78 in prostate cancer will began in spring 2017.Additional NIR conjugates such as carbonic anhydrase IX (CA IX)-targeted NIR agent (OTL338), gamma-glutamyl transpeptidase (GGT)-targeted NIR agent (OTL528), and cholecystokinin 2 receptor (CCK2R)-targeted NIR agent (OTL81) are under clinical development for renal, colon, liver, breast, lung, head and neck and pancreatic cancers.Within five years, OTL will have a solution for imaging most, if not all, solid tumours.These same ligands can also be conjugated to a photodynamic therapeutic (PDT) agent giving surgeons the option to burn targeted lesions as well as visualise them using the same light source and camera.A lead folate-PDT compound (OTL228) has been identified with others to follow. Using OTLs revolutionary fluorescent optical imaging technology, patients are injected with the appropriate probe two hours prior to surgery.During surgery an NIR camera system illuminates the labelled cells,displaying their precise location on a flat screen monitor directly adjacent to the patient.Most camera systems can be used for both minimally invasive and open procedures providing physicians and surgeons with the tools to routinely see diseased cells less than a millimetre in size.Improving detection will also improve diagnosis and staging resulting in a more appropriate treatment.Taken together,better surgery and treatment will improve the outcome for a cancer patient.OnTargets surgical imaging technology is expected to become a new standard of care in cancer surgery in the near future. OTL team OTL is led by a well-rounded four member team that each has expertise in different areas that blend well for the companys success. Philip S Low,PhD,is one of the co-founders and chief scientific officer (CSO) of the company. He has published over 350 scientific articles in peer- reviewed journals and holds over 50 US and foreign issued/pending patents. Seven drugs stemming from this research are currently undergoing clinical trials in three companies (Endocyte, On Target Laboratories, and HuLow) that he co-founded. Sumith A Kularatne, PhD, is the vice-president of research and development at OTL. He has pioneer experience in drug designing on both small molecule lignads and antibody-targeted drugs under the guidance of Dr Low at Purdue University,West Lafayette, Indiana, and Peter G Schultz at The Scripps Research Institute, San Diego, California. Sumiths scientific efforts have resulted in six drug candidates in human clinical trials, over 30 US and foreign issued/pending patents and over 30 peer-reviewed publications. Martin R Low,MBA,is the CEO of OTL.He has founded or co-founded seven companies in insurance, renewable energy, consulting, retail and healthcare. He introduced several innovative products that won awards from BusinessWeek,TheThomas Edison Foundation and the Smithsonian Institute.Tim Biro, MBA, is the chief operating officer of OTL. He has entrepreneurial experience in the medical device and pharmaceutical industry serving as the CEO of several companies including SpineMatrix, MORK Process, Therox Pharmaceuticals and OncoImmune. He also has extensive experience in venture capital, as the founder and managing partner of Ohio Innovation Fund, and a partner in Reservoir Venture Partners.