Ori Hadomi, CEO Since its founding 15 years ago, Mazor Robotics (NASDAQ, TASE:MZOR) has overcome challenges typical to medical device startups to become the leader and possibly the standard of care in spine robotics surgery. “For many early years, adoption of our technology was very slow because we put much more effort into improving the technical aspects of our systems, without focusing on the experience of surgeons using our systems,” Ori Hadomi, CEO, says in an interview with BioTuesdays. “When we began work more with surgeons to promote the user friendly experience of our systems, we reached a turning point in how we looked at development of our products,” he recalls. “It made us realize that realizing our mission of healing through innovation and helping patients would require focus beyond improving our technology.” From Vision to Experienced Market Leader Mr. Hadomi also points out that as a pioneer in spine robotics, the company was educating the market and raising awareness. "We have successfully shifted the question from whether or not a robot is necessary in the spine OR to an understanding that this is the future." Today, Mazor’s core technology has evolved with three generations of commercial products. They include SpineAssist, which was approved by the FDA in 2004; the Renaissance Guidance System, which was launched in 2011 and is installed in four continents; and the Mazor X Surgical Assurance platform, which was launched in the U.S. in mid-2016 and received CE mark approval in Europe last month. Renaissance is an Easy-to-use trajectory guidance system for spine and brain surgeries Mr. Hadomi explains that Renaissance is an easy-to-use trajectory guidance system for spine and brain surgeries, while Mazor X is a state-of-the-art surgical platform with pre-op analytics and intra-op guidance for spinal procedures. As a result, the company now has more than 100 robotic systems in clinical use worldwide. And they have been used in more than 25,000 patient procedures as well as for placing 150,000 implants, he adds. Mr. Hadomi says that with the arrival of the Renaissance robotic system, Mazor made a key decision by establishing two teams in the company: one focused on direct sales and the other targeting supporting assimilation of the technology and supporting surgeons with their cases. “This developed a high level of trust with surgeons and supported adoption of Renaissance in the operating room,” he recalls. “So, what took us 10 years with our first generation product, took us three years with Renaissance.” As the company was working on adoption of Renaissance through a direct sales force in the U.S. and distributors globally, it was developing the Mazor X robotic system, which “moved us in a whole new direction, expanding the role of robotics beyond just guidance,” Mr. Hadomi points out. To realize the potential of the Mazor X breakthrough, the company decided to partner distribution of the new robotic system. “We wanted a deal that would accelerate our growth but only with a partner that would make Mazor X a strategic product in their portfolio,” Mr. Hadomi points out. In mid-2016, Mazor inked a commercial investment agreement that made Medtronic (NYSE:MDT) the exclusive global distributor of the Mazor X platform. The strategy seems to be working. Earlier this month, Mazor said it expects to report record revenue of about $17.2-million for the third quarter this year. For the first half of 2017, revenue rose to $27.2-million from $14.7-million a year ago. Mazor received orders for 22 systems in the third quarter from customers in the U.S., Asia and Israel, of which 19 were for the $1.2-million Mazor X system and three were for Renaissance by Mazor’s distributor in China. Eleven of the 19 orders were by Medtronic, of which five were delivered in the quarter. As of Sept. 18, 2017, Medtronic assumed full responsibility for the distribution of the Mazor X system, as part of the second phase of the commercial agreement between the companies. Medtronic also made a further $40-million equity injection in Mazor, raising its total investment to $72-million. Mazor's system backlog at the end of the third quarter was 17 systems, consisting of 15 Mazor X and two Renaissance systems. Mr. Hadomi says that during the third quarter, Mazor transferred approximately 30 members of its sales team along with its sales pipeline to Medtronic. “The transition was performed in a smooth and effective manner and we maintained a robust sales activity during the transition period,” he adds. Earlier this month, Mazor hired Ron Tavlin, a former consultant supporting Medtronic ventures and corporate development teams, as VP of business development. According to Mr. Hadomi, Mr. Tavlin will lead the implementation of strategies to develop Mazor’s business beyond its current spine focus as “we pursue our goal of being the leader in image-based medical robotics.” Specifically, he says the company will continue to focus on bone anatomy, “exploring internal and external innovations.” Mazor X Surgical Assurance Platform via Features | BioTuesdays by Kilmer Lucas IR http://ift.tt/2hqpzdh
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William McVicar, president and CEO Flex Pharma (NASDAQ:FLKS) expects to report clinical readouts in 2018 from three Phase 2 studies of its anti-cramping drug candidate, FLX-787, in amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth disease (CMT) and multiple sclerosis (MS). “Muscle cramps cause significant morbidity in these severe neurological diseases and there is no FDA-approved treatment,” William McVicar, president and CEO, says in an interview with BioTuesdays. “Our innovative treatments for painful and debilitating muscle cramps and spasticity are based on novel insights in neuromuscular physiology from our co-founder, Dr. Rod MacKinnon, who shared the 2003 Nobel Prize in chemistry for his structural and mechanistic studies of ion channels,” he adds. Mr. McVicar explains that FLX-787 acts by activating two proteins, the TRPA1 and TRPV1 ion channels, which are expressed in mouth and pharynx sensory nerves. “Activation of these nerves is believed to trigger a signal that travels up to the brain, where it is processed, sending a signal through descending spinal cord pathways and slowing down the firing of lower motor neurons,” he suggests. Until recently, it was believed that cramps were caused by dehydration, lactic acid build-up or electrolyte imbalances affecting the muscle. According to Mr. McVicar, new research indicates that muscle cramps and spasms are caused by a neural mechanism: excessive firing of motor neurons in the spinal cord that control muscle contraction. “Neurodegenerative disease induce this hyperexcitability through diminished inhibition, causing them to fire excessively and trigger cramping,” he adds. The Origin of Muscle Cramping Roth analyst Michael Higgins, who reinitiated coverage of Flex last month, said Flex has developed a novel but validated approach to cramp therapy. Mr. Higgins noted that this entirely novel mechanism of action has been evaluated by Flex in proof-of-concept trials using the mixture or FLX-787 in both healthy volunteers and nocturnal leg cramp patients. “Results include reduced cramp intensity and duration lasting up to eight hours and reduced cramp frequency and pain over a two-week daily dosing period,” he added. Mr. Higgins rates the stock at “buy” with a price target of $14. The shares closed at $3.34 on Friday. There are up to 20,000 patients in the U.S. with ALS/motor neuron disease and 55% of ALS patients with pain attributed that pain to muscle cramps. Cramps are of sufficient severity to cause 57% of ALS patients to seek treatments directed at limiting cramps. In addition, increased pain and decreased mobility negatively impact quality of life in ALS patients and are typically associated with increased depression. CMT is a hereditary neurological disease that affects the peripheral motor and sensory nerves motor of the body. Motor nerves control muscle contractions, movement and other activities involving muscles, such as speaking, breathing and swallowing. Symptoms include muscle weakness, abnormal gait and foot deformities. CMT affects about one in 2,500 people in the U.S., approximately 150,000 patients. In CMT, about 70% of patients report cramping. As in ALS, the presence of muscle cramps in CMT patients is consistent with the hypothesis that motor neuron dysfunction and hyperexcitability underlie muscle cramps, which are a function of the underlying disorder. Mr. McVicar says FLX-787 is an orally disintegrating tablet designed to stimulate nerves in the mouth and throat. “Selective chemical stimulation of the vagal, glossopharyngeal, and facial nerves, resets descending inhibition via the spinal cord.” In addition, he points out that electrical stimulation of the vagal nerve is FDA approved for treatment-resistant epilepsy, treatment-resistant depression and, earlier in 2017, for cluster headaches. The company’s early human testing of FLX-787 demonstrated that co-activation of the TRPA1 and TRPV1 ion channels reduced the intensity of muscle cramping, with an onset of action in 15 minutes and a duration of action of up to eight hours. More than 200 individuals have been tested with FLX-787 and/or its natural extracts for safety and anti-cramping activity. Initial pharmacokinetic data detected no drug in the blood stream. In addition, there have been no drug-related severe adverse events with the drug. In addition to its clinical programs, Flex Pharma has developed a consumer product for exercise-associated muscle cramps based on the same mechanism of action as FLX-787 In 2016, Flex initiated a Phase 2 efficacy study in MS patients in Australia. The crossover study is designed to evaluate the safety and efficacy of FLX-787 in approximately 60 patients who suffer from cramps, spasms and/or spasticity as a consequence of MS. Data should be available in the first quarter of 2018. In the third quarter next year, Flex expects to report data from ongoing parallel Phase 2 studies in ALS and CMT. Some 100 subjects in each study are receiving either 30mg of FLX-787 three times daily or a control. ALS and CMT patients are being evaluated for changes in cramp frequency as the primary endpoint, with a number of secondary endpoints, such as pain and quality of life. FLX-787 has received fast track designation from the FDA for the treatment of severe muscle cramps associated with ALS. In addition to its clinical programs, Flex Pharma has developed a consumer product for exercise-associated muscle cramps based on the same mechanism of action as FLX-787. The beverage, called HOTSHOT, is a proprietary blend of capsicum, cinnamon and ginger extracts dissolved in a lime juice-flavored base. PipEline via Features | BioTuesdays by Kilmer Lucas IR http://ift.tt/2yF1A3F Luc Tanguay, president and CEO If approved by the FDA in the next few months, ibalizumab for patients with multidrug resistant HIV has the potential to be a game changer for Theratechnologies (TSX:TH). The FDA accepted ibalizumab for priority review in the summer, with a PDUFA decision date by Jan. 3, 2018. “This approval would make us a leader in niche products for HIV patients, a market segment that is often overlooked,” Luc Tanguay, president and CEO, says in an interview with BioTuesdays. “Our sales force is ready to begin selling ibalizumab immediately after approval.” Adds Philippe Dubuc, SVP and CFO, “Ibalizumab represents the first new anti-retroviral class of drugs for HIV in 10 years, the first non-daily treatment for HIV and the first monoclonal antibody for HIV.” In addition, he points out that there is no drug-drug interaction and no cross-resistance with ibalizumab, which is critical among HIV patients with multidrug resistance. “Ibalizumab works by blocking entry of the virus into healthy cells, preventing the virus from replicating.” Unlike other antiretroviral agents, ibalizumab would be administered intravenously once every two weeks. Philippe Dubuc, SVP and CFO Mr. Dubuc explains that ibalizumab binds primarily to the second extracellular domain of the CD4+ T-cell receptor, away from major histocompatibility complex 2 molecule binding sites. It potentially prevents HIV from infecting CD4+ immune T-cells while preserving normal immunological function. According to Theratechnologies’ estimates, the U.S. HIV-infected population stands at 1.2 million individuals, of which 450,000-to-650,000 people are being treated. The European population is estimated to be of a similar size. Mr. Dubuc says the company figures there are 20,000-to-25,000 multidrug resistant HIV patients in the U.S., of which the annual population requiring new treatment is 10,000-to-12,000 a year. “This would be our focus with ibalizumab,” he adds. “We have already guided that, if approved, ibalizumab would sell at a premium to other HIV drugs on the market, so our target patient population would represent a $500-million total market opportunity.” If approved by the FDA, ibalizumab would have 12 years of regulatory exclusivity in the U.S. CIBC World Markets analyst, Prakash Gowd, rates Theratechnologies at “outperform” with a price target of $10.30. “Given its breakthrough status, as well as a clear unmet medical need addressing multidrug resistant HIV, ibalizumab may be approved in advance of the Jan. 3 PDUFA date.” The stock closed at xxx on Friday. “We expect Theratechnologies stock to outperform as it runs into a possible year-end approval,” Mr. Gowd said in a September research report. Theratechnologies, which acquired the commercial rights for ibalizumab from TaiMed Biologics of Taiwan in March 2016, already has a presence is the niche HIV products segment with its FDA-approved EGRIFTA for the treatment of HIV-associated lipodystrophy, a common side effect of antiretrovirals that causes body fat to be abnormally redistributed. Earlier this year, the companies expanded their partnership to cover sales of ibalizumab in Europe, which Mr. Dubuc figures could start in 2020, following an application for regulatory approval. TaiMed currently is working on an intra-muscular formulation of ibalizumab, as well as a once monthly formulation. EGRIFTA is the only FDA-approved drug shown to reduce excess abdominal fat in people living with HIV and affected by lipodystrophy. There are 15,000 severe cases of HIV-associated lipodystrophy in the U.S. The drug, which is also approved in Canada and Mexico, has been on the market for seven years and Theratechnologies is guiding to sales of $42-million to $44-million in 2017, up from $37-million in 2016. “EGRIFTA’s sustained cash flow has helped us acquire the commercial rights for ibalizumab and build our sales team in preparation for the launch of ibalizumab,” Mr. Tanguay contends. Theratechnologies has expanded its sales team to 41 people to promote EGRIFTA and ibalizumab, when approved, up from 12 people in 2016. The reimbursement and medical science liaison teams also are expected to grow to 11 from four. “Our expanded team should reach 95% of the 5,000 most important physicians in the U.S. treating HIV and key opinion leaders, up from around 1,000 physicians last year,” Mr. Tanguay suggests. EGRIFTA also would benefit from the expanded commercialization team in the U.S. “We are also working on expanding our product portfolio through either product acquisitions or in-licensing deals,” he adds. “We would like to add one or two additional products to gain operating efficiencies from our expanded sales force.” In a pivotal trial with ibalizumab, 82.5% of patients achieved the primary endpoint, with an average viral load reduction of 1.1 log 10 after seven days and no treatment-related severe adverse events. “The outcome was beyond our expectations,” Mr. Dubuc admits. At the end of the 24-week trial, the mean reduction in viral load was 1.6 log 10 and 43% of patients achieved undetectable viral load, with a mean reduction of 3.1 log 10. “These results give us a very high confidence in FDA approval,” he adds. Earlier this month, Theratechnologies presented additional positive safety and efficacy results for ibalizumab in patients who completed the 24-week Phase 3 study and continued treatment in an expanded access program. “This long-term data reinforces the critical role ibalizumab could have for patients struggling with multidrug resistant HIV,” Mr. Dubuc points out. via Features | BioTuesdays by Kilmer Lucas IR http://ift.tt/2ikDSU4 Dr. Kate Beebe, EVP & chief development officer After gaining widespread attention with its FDA-approved Probuphine implant for the maintenance treatment of opioid addiction, Titan Pharmaceuticals (NASDAQ:TTNP) is setting out to develop an implant to treat Parkinson’s disease (PD). Last week, Titan initiated screening of the first patients in a Phase 1/2-dose escalation trial with an implant containing the drug ropinirole, a dopamine agonist sold by GlaxoSmithKline for PD under the brand name, Requip. “We expect to enroll about 20 patients with idiopathic PD at three sites in the U.S. in four cohorts of five patients each,” Dr. Kate Beebe, EVP and chief development officer, says in an interview with BioTuesdays. “Patients in the first cohort will receive one implant, patients in the second cohort two implants, the third cohort three implants, and patients in the fourth cohort will receive four implants, which we expect should cover the prescribed range of daily oral doses of ropinirole,” she adds. Data from the first patient cohort should be available in early 2018, following completion of three months of treatment. The study should be finished by the end of 2018. Dopaminergic neurons in brain Dr. Beebe explains that PD is characterized by the loss of dopamine, which alters activity in the brain region impacting movement and motor function, as well as mood, insomnia, anxiety, appetite and other non-motor symptoms. The disease is treated with drugs designed to replace or mimic dopamine in the brain. But after several years of daily dosed treatment, these drugs can lose their benefit and trigger serious side effects in up to 80% of patients, she adds. “This is where we think our implant can play an important role.” According to Dr. Beebe, PD affects as many as one million people in the U.S., with that number expected to almost double by 2030 because of the aging population. In addition, there are some 60,000 newly diagnosed cases of PD annually and more than 23,000 die from PD each year. A 2013 study by the Parkinson’s Action Network, National Center for Health Statistics determined that PD costs American society some $14.4-billion annually, comprised of treatment costs of $8.1-billion and indirect costs of $6.3-billion, with total costs expected to double by 2040. Dr. Beebe says Titan’s ropinirole implant, which like Probuphine is based on the company’s ProNeura drug delivery platform, has been evaluated in a PD animal model. The implant facilitates a controlled rate of drug delivery, is virtually 100% bioavailable, with no reservoir and no risk of drug dumping. The ProNeura technology uniformly distributes an active pharmaceutical ingredient throughout an ethylene vinyl acetate polymer, which is blended and extruded, to produce a rod shaped implant. The implant facilitates a controlled rate of drug delivery, is virtually 100% bioavailable, with no reservoir and no risk of drug dumping. The non-clinical PD model results were presented at the 19th International Congress of Parkinson's Disease and Movement Disorders in June 2015. Dr. Beebe says the implant demonstrated sustained plasma ropinirole levels for several months following implantation, with no local skin irritation at implant site. The implant also controlled PD symptoms without triggering dyskinesias, or involuntary muscle movements. She says the goals of the Phase 1/2 trial include characterizing the pharmacokinetic profile of the ropinirole implants, evaluating safety and tolerability of up to four dose levels and exploring potential signals of efficacy using established disease-specific assessment scales. ProNeura offers continuous drug delivery and consists of a small, solid rod made from a mixture of ethylene-vinyl acetate (EVA) and a drug substance. Sunil Bhonsle, president and CEO says the company is continuing discussions with potential partners to distribute its Probuphine implant in Europe. “We’re focused on areas in Europe where the active ingredient in the implant, buprenorphine, is already being sold. There’s also a potential for commercial distribution in Australia and some areas in Asia.” The company plans to submit a marketing authorization application for Probuphine to the European Medicines Agency in the fourth quarter this year. Probuphine is sold in the U.S. by Braeburn Pharmaceuticals. Beyond PD, Mr. Bhonsle says an implantable triiodothyronine (T3) product for the treatment of hypothyroidism is completing non-clinical development focused on formulation optimization. Titan also is collaborating with the Walter Reed Army Institute of Research and the Southwest Research Institute in the early non-clinical evaluation of the implant drug delivery platform in malaria prophylaxis, and with Opiant Pharmaceuticals (NASDAQ:OPNT) in the feasibility assessment of an implant to provide continuous, long-term treatment with an opioid antagonist for the potential prevention of opioid relapse and overdose in patients with opioid use disorder, he adds. Other ProNeura feasibility evaluations are ongoing in the area of chronic pain treatment with a peripherally acting, Kappa opioid receptor agonist, and in the treatment of Type 2 diabetes with currently approved peptides. via Features | BioTuesdays by Kilmer Lucas IR http://ift.tt/2y7qzww Diffusion Pharmaceuticals (NASDAQ:DFFN) expects to begin before the end of 2017 a pivotal clinical trial with its trans sodium crocetinate (TSC) lead compound to re-oxygenate oxygen-deprived tissue in patients with inoperable glioblastoma (GBM) brain cancer prior to conventional radiation and chemotherapy. “In our Phase 2 study, we observed a 37% increase in overall survival at two years, but in a subset of patients with inoperable GBM, survival rose fourfold at two years,” David Kalergis, chairman, CEO and co-founder, says in an interview with BioTuesdays. “This highly responsive subset will be the focus of our Phase 3 trial.” The Phase 2 study, which enrolled 59 newly diagnosed GBM patients, also demonstrated a clean safety profile and tumor regression, with 11 patients having undetectable tumors. There were no serious adverse events attributed to TSC and no negative effects on quality of life. Results of the study were published in the Journal of Neurosurgery in February 2017. Mr. Kalergis explains that an insufficient oxygen supply, or hypoxia, to a region of the body causes major clinical problems in many life-threatening diseases. “Hypoxia is an especially critical obstacle in the treatment of cardiovascular and respiratory diseases, as well as in cancer.” In cancer, he points out that hypoxia, which occurs when the cancer outgrows its blood supply, can lead to aggressive tumor characteristics, such as increased angiogenesis, metastatic potential and resistance to treatment with radiation and chemotherapy. Source of demographic/market data: Cowen & Co., Therapeutics Categories Outlook “Our TSC re-oxygenates hypoxic tissue systemically in many disease settings, including cancerous tissue,” he contends. The company has orphan drug designation from the FDA in multiple indications, including GBM. GBM is the deadliest form of brain cancer, with an average life expectancy post-diagnosis of less than two years. In the U.S. alone, approximately 18,000 people are diagnosed with GBM every year. Diffusion also is developing TSC as potential treatments for metastatic brain cancer and metastatic pancreatic cancer. Beyond oncology, the company’s other hypoxia-related indications, which are supported by preclinical and clinical data, include:
TSC was developed at University of Virginia by Prof John Gainer, Diffusion’s co-founder, under a grant from U.S. Office of Naval Research as an emergency treatment for battlefield casualties suffering life-threatening hypoxia from blood-loss. “We transitioned to oncology as a first focus, based on promising preclinical, and human safety and efficacy data,” Mr. Kalergis points out. When TSC is added to an aqueous solution like blood plasma, he says it causes the aqueous molecules to form more hydrogen bonds with each other. Additional hydrogen bonds change the molecular structure of the aqueous portion of blood plasma. And a more open molecular structure allows oxygen to more easily diffuse into hypoxic tissue. “We have validated the mechanism of action through computer simulation studies, in vitro studies and direct oxygen measurement in tissue,” he adds. “TSC has been studied in three Phase 1 or 2 studies and has demonstrated a favorable safety profile, clinical efficacy and optimal dosing regimens. We are Phase 3 ready.” According to Mr. Kalergis, inoperable GBM patients are currently excluded from major clinical trials, highlighting the unmet need and making these patients available for the TSC Phase 3 trial. Based on an end-of-Phase 2 meeting with the FDA, a single Phase 3 study, if successful, could serve as a basis for regulatory approval, he adds. The company expects to enroll 230 newly diagnosed inoperable GBM patients, randomized 1-to-1 into TSC treatment and control groups. Under the protocol, after patients are determined to be inoperable, they would receive TSC dosing immediately prior to an initial six weeks of radiation and chemotherapy. Following a rest period, patients again would receive TSC immediately prior to a 24-week regimen of only chemotherapy. The primary endpoint of the trial is overall survival; secondary endpoints are tumor status, performance and quality of life. Mr. Kalergis figures the Phase 3 trial will take 3 ½ years to complete. Diffusion also has orphan drug designation for TSC as a treatment for metastatic brain cancer, which also is highly hypoxic and causes significant resistance to the current standard of care, which is radiation treatment. In a rat study of metastatic brain cancer, Mr. Kalergis says radiation plus TSC resulted in a 73% survival rate at 60 days, with complete tumor remission in TSC survivors, based on MRI. That compared with 28% survival at 60 days in a radiation-only treatment group, also based on MRI. PET scan showing hypoxia levels in rat brain tumor, before and after TSC. In pancreatic cancer, another very hypoxic cancer, he says various animal studies have shown TSC to be a significant enhancer of standard-of-care chemotherapies: gemcitabine and paclitaxel. “We have protocols completed for these two cancer indications but have not submitted them to the FDA because we are focusing our resources on the Phase 3 GBM trial,” he adds. “As a result, we are looking for partnerships or out-licensing the metastatic brain and pancreatic indications.” Having proven safety from the company’s oncology studies would allow the company to begin additional Phase 2 studies for other hypoxia-driven indications beyond oncology, “assuming partnerships or other funding,” he contends. In stroke, for example, hypoxia drives the destruction of neurons in the brain, leading to impairment and death. Mr. Kalergis notes that the company has obtained statistically significantly safety and efficacy results in animal studies with TSC alone and in combination with tPA, a clot buster that is the standard of care in both ischemic and hemorrhagic stoke, respectively. “We’re working with key opinion leaders on a stroke clinical trial design, but here again we’re looking for some sort of partnership.” he adds. via Features | BioTuesdays by Kilmer Lucas IR http://ift.tt/2xRjzRT |
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