Kevin Sullivan, MBA Closely-held Appili Therapeutics plans to begin late in the current quarter a Phase 1 bridging, or bioequivalence, study of its lead anti-infective, ATI-1501, a reformulated, taste-masked liquid suspension of metronidazole, targeting anaerobic bacterial infections, including Clostridium difficile. “Our product has the potential to overcome the very bitter taste of metronidazole when it is crushed and administered to many pediatric and geriatric patients who have difficulty swallowing and must take the medication three times a day for up to two weeks,” Kevin Sullivan, CEO, says in an interview with BioTuesdays. “Making metronidazole more palatable is a significant market opportunity,” he contends. Metronidazole has been on the market as a tablet in North America for more than 50 years and has been a workhorse in the field, with some 9.5 million annual prescriptions in the U.S. alone. Metronidazole also is on the WHO list of essential medicines. And despite its widespread use, relatively low levels of resistance have developed against it over the years, Mr. Sullivan points out. “Our initial focus is on the more than one million pediatric and/or geriatric patients who have difficulty swallowing and are afflicted with diseases where metronidazole is the first line of therapy,” he says. “This is where we expect adoption to be the highest.” Appili, which was founded in May 2015 by investment banker, Bloom Burton, also is in early research for a second anti-infective drug, ATI-1503, a negamycin analogue development program that continues work started at AstraZeneca after it exited the antibiotic sector in 2014. According to Mr. Sullivan, negamycin analogues have broad activity against Gram-negative bacteria, including three of the CDC’s most urgent threats: Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. “Our goal at the outset was to build a balanced risk portfolio, with potentially faster-to-revenue compounds, like ATI-1501, which would give us the flexibility to take on a higher risk but truly transformational compound, like ATI-1503,” he adds. “We are looking to grow our pipeline substantially over the next few years with faster-to-revenue programs.” Product Pipeline Mr. Sullivan says Appili met with the FDA in February to discuss the clinical program for ATI-1501 and has begun GMP manufacturing clinical batches for its 40-patient Phase 1 study. A subset of patients will advance into a tasting component in order to obtain subjective feedback from ATI-1501 and the standard of care, he adds. Appili hopes to file a NDA, using the 505(b)(2) pathway, in the first quarter of 2018, with possible market approval in early 2019, he adds. “We will be able to advance our filing with all publicly available scientific data associated with metronidazole.” In addition, the company has retained Torreya Partners to seek an out-licensing agreement for ATI-1501 and has a data room available for potential partners to evaluate its full commercial potential. To gauge physician interest in ATI-1501 and build a business case for the company, Appili and Market Street Research conducted a study of 263 physicians treating geriatric patients. According to a 2014 study by the Review on Antimicrobial Resistance, there are more than two million people afflicted with drug resistant infections, with forecasts of 10 million deaths annual by 2050. The WHO considers antibiotic resistance one of the three greatest threats to mankind. Mr. Sullivan also notes that the FDA has adopted a number of R&D and regulatory incentives to foster development of anti-infectives, including additional market exclusivity, priority review, fast track approval and priority review vouchers. “This is also a priority research area for NIH, CDC and U.S. military funding,” he adds. To gauge physician interest in ATI-1501 and build a business case for the company, Appili and Market Street Research conducted a study of 263 physicians treating geriatric patients. The research found 94% of physicians treating the elderly were interested in a taste-masked liquid oral formulation of metronidazole, with 63% of long-term care physicians very interested. “A pricing strategy is very important with our potential product because metronidazole is relatively inexpensive for a 10-to-14 day regimen,” Mr. Sullivan points out. “If there are issues with metronidazole in hospitals and institutions treating C. difficile, for example, physicians typically switch patients to Vancomycin, which costs more than $300 per regimen.” Appili and QuintilesIMS surveyed 11 insurance payers, representing 56 million lives and a broad cross-section of managed care facilities, finding that payers considered ATI-1501 good value in the $200-to-$250 range per regimen. Citing a more than one million target population of seniors with difficulty swallowing metronidazole, Mr. Sullivan figures ATI-1501 has an annual market opportunity of $75-million to $200 million, depending on market penetration. On the other hand, the market potential for Appili’s ATI-1503 exceeds $1-billion, as it represents a “starting point for a new class of Gram-negative targeting agents,” he contends. The company has attracted Dr. Sridhar Narayan, who managed the negamycin program at AstraZeneca, to its scientific advisory board. Mr. Sullivan says the major advancement at AstraZeneca was to improve the compound’s potency so that less drug was needed to kill the bacteria. Appili hopes to identify a clinical lead and establish animal proof-of-concept for ATI-1503 in 2018. “Gram-negative bacteria has become a global threat because its surrounding molecular structure makes entry of antibiotics difficult,” he adds. “Our ATI-1503 naturally enters Gram-negative bacteria, so our goal now is enhancing that entry. A lot of pharma companies in the infectious disease space are watching our program.” via BioTuesdays Features - BioTuesdays http://ift.tt/2v2XfG4
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Bharatt Chowrira, president and chief of business and strategy With eight clinical-stage studies underway, including two pivotal trials expected to readout later this year, PureTech Health (LSE:PRTC) is taking a novel approach to drug development, targeting serious diseases caused by dysfunctions in the brain, gut and immune system. “We believe these three body systems are interconnected in a number of different ways that underlie chronic diseases,” Bharatt Chowrira, president and chief of business and strategy, says in an interview with BioTuesdays. “So that by understanding the underlying biology affecting the brain, gut and immune system, and the dysfunctions in these three systems, we can tackle chronic diseases effectively,” he adds. Dr. Chowrira explains that PureTech is focused on slowing, halting, or reversing disease progression in chronic diseases that are the biggest burden to the healthcare system, accounting for 85% of healthcare costs. “Oftentimes, when a patient sees his or her doctor, their disease is too advanced to change the course of the disease. At this point, only maintenance therapy is available so the disease does not progress. Our focus is to detect and intervene early in a chronic disease with a treatment that has a chance at changing the direction of the disease.” Dr. Chowrira explains that PureTech is focused on slowing, halting, or reversing disease progression in chronic diseases that are the biggest burden to the healthcare system, accounting for 85% of healthcare costs According to Dr. Chowrira, the approach of some biopharma companies has been to develop a “therapy or solution and then look for a human problem to solve, which can often result in a low success rate. Our approach is to start with a problem and then identify innovative approaches to address it.” For example, Dr. Chowrira explains that in PureTech’s late-stage GI program, the challenge was that obesity and obesity-related comorbidities represent a global health challenge, with medical costs exceeding $190-billion annually in the U.S. alone, making this area a high priority for health insurance companies. “So we put together a group of key opinion leaders to understand the drawbacks of existing approaches with pharmaceuticals and bariatric surgery, especially for those patients who are not morbidly obese,” he adds. “And we came up with this idea: what if you could have an effective oral therapy that acts mechanically in the GI tract, but without the invasive procedure of bariatric surgery and side effects of weight loss drugs?” The result, he contends, is Gelesis100, which is orally administered and has the potential to be a transformative treatment. It is designed to be safe and efficacious and work mechanically in the gastrointestinal system. The FDA and European regulators are treating Gelesis100, PureTech’s lead program, as a medical device, which makes the hurdle for approval lower. In a mechanical solution, he says, the body does not absorb a drug, but the outcome is similar to surgical interventions like gastric balloons. Specifically, a patient feels less hungry, takes in less food and the food that is eaten, is absorbed more slowly. All of which leads to weight loss and improved comorbidities, such as diabetes. Dr. Chowrira explains that Gelesis100 is scientifically grounded with two safe building blocks: a modified cellulose and citric acid found in fruits. By cross-linking the two components in a novel matrix, he says Gelesis100 is a hydrogel, swelling with water and occupying a certain volume in the GI tract, thus creating the feeling of fullness so a patient eats less. And as it passes through the GI tract, it does not interfere with the body’s ability to absorb nutrients from food, he adds. In an earlier three-month human proof-of-concept study with 125 patients, a 2.25-gram dose of Gelesis100 achieved a statistically significant 6.1% total body weight loss, Dr. Chowrira says. In 29 prediabetic patients, there was an even greater 10.9% total body weight loss. In addition, 56% of prediabetic patients returned to normal glucose status. PureTech’s six-month pivotal trial with Gelesis100 in the U.S. and Europe is fully enrolled with 436 overweight and obese patients, including about 30% who have been diagnosed with prediabetes and mild Type 2 diabetes. Dr. Chowrira says top-line data is expected later this year. The co-primary endpoints include a 3% or greater placebo-adjusted weight loss and a total weight loss of 5% or greater in 35% or more patients. A secondary endpoint is change is glycemic control parameters. In an earlier three-month human proof-of-concept study with 125 patients, a 2.25-gram dose of Gelesis100 achieved a statistically significant 6.1% total body weight loss, Dr. Chowrira says “Gelesis100 has a unique opportunity to target many chronic diseases associated with obesity,” Dr. Chowrira says, pointing to Type 2 diabetes, non-alcoholic fatty liver disease, osteoarthritis and cardiovascular disease. “Treatments for all of these diseases suggest that a sustained weight loss of 3% to 5% would have clinically meaningful health benefits,” he adds. “Yet there is nothing doctors feel comfortable prescribing primarily due to safety concerns. So, we see a good potential for Gelesis100 to be prescribed along with any treatment for diabetes, for example.” The company also is testing Gelesis 200, a second product candidate, to potentially address other GI conditions, including glycemic control, and inflammatory bowel and liver disease, with proof-of-concept and preclinical studies scheduled to readout later this year and in mid-2018. PureTech has taken a similar approach in its immune system program, where Dr. Chowrira says the aging population presents a looming global healthcare crisis, attracting massive investments in innovation. Despite these efforts, he contends that many of the afflictions of aging, such as immunosenescence, are unmet medical needs. Immunosenescence is the gradual weakening in the ability of the aging immune system to fight off respiratory tract infections that are particularly common during winter cold and flu season. “Limited therapeutic options exist today to prevent and treat patients with respiratory tract infections.” Pneumonia and influenza are the fourth and eighth leading causes of death in people aged 85 and 65, and over, respectively, in the U.S. In addition, hospitalizations for respiratory tract infections increase the risk of people over the age of 85 being admitted to a nursing home. To tackle the problem, the company set out to utilize the mTOR pathway, by selectively targeting mTORC1, which has been linked in animal and human studies to immunosenescence and other diseases of aging. “By selectively inhibiting mTORC1, we believe we can boost the immune system to reverse age-related immunosenescence,” he suggests. Dr. Chowrira says the company in-licensed two compounds for aging-related indications from Novartis, which had previously explored the immune-enhancing potential of the compounds in two successful Phase 2a studies with almost 500 elderly patients. The results from one of those studies are being submitted to a peer-reviewed journal later this year. PureTech is now testing its RTB 101 compound in a Phase 2b trial in elderly subjects at a high risk of respiratory tract infections. The primary endpoint is percentage reduction in respiratory tract infections during 16 weeks of winter cold and flu season. Part one of the trial is currently underway with more than 150 subjects enrolled during winter cold and flu season in New Zealand. An interim analysis later this year will help determine an optimal dose of RTB 101 for the second part of the trial that will enroll up to 430 patients in the U.S. when flu season begins at the end of this year. The Phase 2b data will be released in the second half of 2018. Another PureTech asset in its nervous system focus is Akili, which is developing a treatment for pediatric attention-deficit hyperactivity disorder (ADHD), currently called Project:EVO, and a potential screening device for early diagnosis of Alzheimer’s disease, which has been studied in collaboration with Pfizer. Dr. Chowrira explains that Akili is a digital medicine platform based on cognitive science developed by Dr. Adam Gazzaley at the UCSF and in-house-developed proprietary adaptive algorithms, delivered in the form of an action video game. Dr. Gazzaley’s initial research demonstrated that neural networks in elderly patients could be rewired to improve the ability to perform certain functions. A pivotal trial in pediatric ADHD is expected to readout at the end of 2017. About 20% of children with ADHD do not respond to current treatments and 30% are not treated. “The challenge with Alzheimer’s has been an inability to find patients early enough with the disease,” Dr. Chowrira points out. “By the time they exhibit symptoms, they do not respond to therapies and drugs in clinical development have failed. Our approach has the potential to detect people at risk of developing Alzheimer’s long before they develop symptoms.” Data supporting this approach were recently presented by Pfizer at the International Conference on Clinical Trials for Alzheimer's disease. Product Pipeline via BioTuesdays Features - BioTuesdays http://ift.tt/2u5ghKv president and ceo, john gannon As president and CEO of closely-held Blue Spark Technologies and co-inventor of its newest product, TempTraq, John Gannon’s career has stretched from the aerospace industry to Wall Street, culminating in 2011 with this developer of thin, flexible printed batteries built on IP from Eveready Battery, now Energizer. He has worked as an engineer in GE’s Astro-Space division and in currency derivatives with Merrill Lynch in New York and Barclays Capital in London, drawing on his background in mathematics, physics, engineering and business administration. In this interview with BioTuesdays, Mr. Gannon discusses Blue Sparks’ TempTraq medical device, a wireless, wearable patch that continuously monitors body temperature for the hospital and home markets. Let’s begin with a brief history of your company. The company was formed in 2003 as Thin Battery Technologies to develop thin, flexible printed batteries built on IP licensed from Eveready Battery, which is now Energizer. In the first few years, we were successful in putting high volume manufacturing in place to commercialize this revolutionary technology. Since 2004, over 300,000 of our thin, printed batteries have been produced and delivered. We then turned our focus to developing applications that required thin, flexible power, were comfortable to wear and could collect data, resulting in our flagship product, TempTraq, which was FDA-cleared as a Class 2 medical device in 2015. And our focus going forward is on wearable medical devices, which can use our technology as a power source. according to gannon, newly developed electronic inks are used to print active devices, such as thin film transistors and thin printed batteries Can you explain the term, printed electronics? Printed electronics is the term used for a relatively new technology that defines the printing of electronic circuits and components on common media such as paper, plastic, and textile, using standard graphic arts printing processes and press equipment. Newly developed electronic inks are used to print active devices, such as thin film transistors and thin printed batteries. Leading-edge companies are currently using the technology to transform basic circuit elements, such as thin-film transistors, resistors, inductors, and capacitors into printed batteries, displays, sensors, radio-frequency identification (RFID) tags, interactive packaging, solar panels, and even speakers. What are the advantages of printed electronics? Some of the advantages are their low cost, and ease of production and integration. In many industries, printed electronics technology is expected to facilitate widespread development of functional electronic devices that can be useful for applications not typically associated with traditional electronics, such as flexible displays, smart labels, animated posters, novelty items and active clothing. Can you describe how this dovetails with TempTraq? Temptraq is a wearable patch consists of a temperature sensor, microprocessor, communication module, with a thin, flexible battery Our wearable patch consists of a temperature sensor, microprocessor, communication module, with a thin, flexible battery, all contained in safe, biocompatible adhesives and foams. The device can take temperature readings, store the reading and then, using low energy Bluetooth technology, communicate the reading out 50 feet to either a gateway capture device or a smart phone or tablet. Why is continuous temperature monitoring important? When we talk to clinicians about overall biometric monitoring, they say temperature is one of the most important vital signs where there hasn’t been any significant evolution in measurement during the past century. The standard of care is single point readings every four-to-six hours, which are manually entered to a patient’s chart. Compare that with finger clips for continuous oxygen readings and continuous readings of blood pressure. We think continuous monitoring of temperature is a trend whose time has come. How does TempTraq work in the clinical setting? The device has a unique identifier on each patch, which is important in the clinical setting because it allows data from a specific patch to align with a patient identifier number. Using our TempTraq Connect, which is a secure, HIPAA-compliant service and supported by Google Healthcare Cloud Platform, our 72-hour disposable patches can integrate directly with hospital central monitoring and electronic health records systems to safely and securely store patient data. The value proposition in hospitals is that by identifying fever earlier, clinicians can intervene faster, leading to better patient care. according to gannon, in terms of the consumer market, the focus has been parents with children under the age of 12 How does TempTraq work in the home market? In the consumer market, our focus has been parents with children under the age of 12. TempTraq currently is being sold in about 15,000 stores nationwide for the home market. An app for an iPhone or Android smart phone receives continuous monitoring of temperature of sick children, adding peace of mind about whether a fever is worsening or improving. The advantage is that you don’t have to wake up a child to get that answer. Is there any clinical data you can discuss? A recent study by University Hospitals Seidman Cancer Center in Cleveland found that the TempTraq patch detected a rise in body temperature up to 180 minutes earlier, in a majority of patient cases, than current standard of care. To study this continuous, real-time method of body temperature measurement, UH tested the feasibility of monitoring body temperature for patients specifically undergoing stem cell transplant or intensive chemotherapy for leukemia. The patches were applied every 24 hours on 10 neutropenic patients throughout their hospital stays. Body temperature was recorded remotely with TempTraq in 10-minute intervals, resulting in more than 14,000 temperature measurements, compared with the current standard standard-of-care of one measurement every four hours. The study results were published in the Journal of Clinical Oncology in May. How do you see TempTraq transforming healthcare going forward? Post-op, a major expense in hospitals is managing patients with sepsis so identifying fever as early as possible can be critically important. TempTraq also has a role in the ER during patient admissions and in intensive care wards. Hospitals are very interested in outpatient monitoring after they send a patient home, with data sent back to a doctor or central nurses’ station. What’s in your pipeline? In addition to the 24-hour patch we are already offering to consumers, we’re preparing to introduce a 48-hour patch for the home market, along with our HIPAA-compliant TempTraq Connect platform. In addition, we are looking to integrate additional sensor capabilities in the platform, a project we will begin in the second half this year. Our current primary focus is wide scale hospital implementation of TempTraq. We view TempTraq as a product that can be used throughout a hospital. via BioTuesdays Features - BioTuesdays http://ift.tt/2uMlnth Andre Rancourt, CEO Tetra Bio-Pharma (OTCQB:TBPMF; CSE:TBP) has an aggressive clinical trial program set to begin in the final quarter this year and first quarter of 2018 to prove the efficacy and safety of at least three therapeutic cannabis products. “We’re also hoping to launch a line of natural health cannabis products by the fall this year to begin generating revenue,” Andre Rancourt, CEO, says in an interview with BioTuesdays. Those natural health products include a topical treatment for pain management; an oral well-being product designed for cardiovascular disease prevention and athletic performance; a topical cream for skin care; and a quality of life topical for women, he adds. “We’ve hired a VP of sales and marketing to work on branding and distribution.” Founded in 2015, Tetra operates through three subsidiaries, including Phyto Pain Pharma, a developer of cannabis-based drug products; Agro Tek, its commercialization arm for natural health products; and Grow Pros, a landowner proceeding with plans to become licensed to grow marijuana. “We are planning to sell Grow Pros because we do not want to be known as a recreational marijuana company, but rather as a global leader in pharmaceutical cannabis and nutraceuticals,” Mr. Rancourt points out. “Cannabis-based drugs have the potential to replace drugs that have toxic side effects, such as steroids.” Canada currently has 43 licensed producers of cannabis and Mr. Rancourt suggests that medical marijuana is an industry that has popped up based on casual studies observing the benefits of smoking marijuana. Founded in 2015, Tetra operates through three subsidiaries, including Phyto Pain Pharma, a developer of cannabis-based drug products; Agro Tek, its commercialization arm for natural health products; and Grow Pros, a landowner proceeding with plans to become licensed to grow marijuana. “Our strategy is to focus on the real science and safety of cannabis so that our products can be approved by Health Canada and the FDA, prescribed by physicians, distributed by pharmacies and covered by insurance companies.” Tetra is developing its lead product, PPP001, to be the first smokeable marijuana for advanced cancer pain. PPP001 has been designed as a pellet to be delivered through a titanium inhalation device, which includes a digital readout so that a pharmacist can monitor an individual’s consumption of cannabis. Tetra has a strategic partnership with Aphria (OTCQB:APHQF; TSX:APH), a leading licensed producer of cannabis, which is supplying the active pharmaceutical ingredient for PPP001. Last month, Tetra reported positive results from a Phase 1 study of PPP001, with safety data meeting the company’s expectations. In addition, pharmacokinetic data demonstrated that inhalation of PPP001 achieved the targeted plasma levels of tetrahydrocannabinol (THC) that could potentially achieve pain relief in cancer patients. The Phase 1 trial also provided key information required to design a Phase 3 clinical trial for cancer patients, which is expected to begin around the end of this year. “Because cannabis is a known chemical entity, we are able to bypass Phase 2 studies and move directly into a pivotal trial,” Mr. Rancourt points out. The company hopes to sign a commercial partnership for PPP001 by the end of 2018 and receive a Notice of Compliance from Health Canada by the end of 2019 to launch PPP001, he adds. In Canada, under the Access to Cannabis for Medical Purposes Regulations (ACMPR), which permits compassionate use of cannabis, Tetra hopes to begin selling PPP001 through pharmacies at the end of the summer. “We will be able to use this legal route to generate revenue,” Mr. Rancourt notes. In addition to pain relief, Tetra expects to demonstrate the clinical benefits of PPP001 on the quality of life of advanced cancer patients. “Our clinical program also will address the potential of PPP001 to reduce the reliance on opioids for management of severe pain,” he adds. Tetra and IntelGenx (OTCQX:IGXT; TSXV:IGX) are jointly developing an oral mucoadhesive dronabinol XL tablet, known as PPP002, which clings to the inside of the cheek and is based on IntelGenx’s AdVersa controlled-release technology. “The sustained-release THC tablet has the potential for a significant reduction of side effects, compared with synthetic THC, for North American patients suffering from anorexia and cancer chemotherapy-related pain,” Mr. Rancourt says. Tetra also plans to develop cannabinoid drugs for the veterinary market and plans to create an advisory board consisting of veterinary specialists in the fields of ophthalmology, oncology and pain. PRODUCT PIPELINE A Phase 1 study of PPP002 has been successfully completed, with a Phase 2 trial slated to begin in the fourth quarter this year, leading to a Phase 3 trial by the end of 2018. Tetra hopes to meet with the FDA’s Division of Anesthesia, Analgesia, and Addiction Products to discuss a 505(b)(2) regulatory filing of PPP002 and marketing requirements for the Dronabinol XL AdVersa Mucoadhesive tablet. For dry eye disorder, ocular pain and inflammation, Tetra and co-development partner, Panag Pharma, have completed preclinical proof-of-concept and non-clinical safety of a cannabinoid eye drop, known as PPP003. Tetra hopes to begin Phase 1 testing of PPP003 at the end of this year in patients with dry eye, which Mr. Rancourt suggests is the most rapid indication for drug approval. Tetra and Panag also are developing a pure THC topical cream, currently known as PPP004, for the treatment of general neuropathic pain, such as exema. “We focus our business model on developing partnerships to take advantage of the proven technology other companies have developed and then working jointly to bring pharmaceutical relevance to these cannabis-based drugs,” he says. via BioTuesdays Features - BioTuesdays http://ift.tt/2slWsLt |
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