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Sunday, December 2, 2018

Apellis Updates Data from Study of Hemoglobinuria at ASH


  • Treatment with APL-2 in eculizumab-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH) resulted in broad control of hemolysis and normalization of mean hemoglobin to 12.2 g/dL by day 85, an increase of 4.2 g/dL from baseline
  • Previously transfusion-dependent patients did not require any transfusions during maintenance treatment with APL-2
  • Rapid and durable normalization Lactate Dehydrogenase, Reticulocyte Count and Total Bilirubin was achieved
Apellis Pharmaceuticals Inc. (Nasdaq:APLS), a clinical-stage biopharmaceutical company focused on the development of novel therapeutic compounds to treat disease through the inhibition of the complement system, today announced interim data from its Phase 1b study of APL-2 in treatment-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH). Data from the PADDOCK trial were presented in a poster session today at the 60th Annual Meeting of the American Society of Hematology (ASH).
Interim results from the ongoing PADDOCK study evaluating 270mg subcutaneous APL-2 administered daily are presented. Data are presented for 19 patients at baseline, 15 patients on therapy at day 85 and 10 patients at day 169.
“There remains a significant unmet need in PNH driven by extravascular hemolysis, which is not addressed by C5 inhibitors such as eculizumab,” said Dr. Cedric Francois, MD, PhD, Apellis co-founder and CEO.  “A recent large study showed that over 70% of PNH patients continue to be anemic and nearly 40% had at least one transfusion in the prior year while on treatment with eculizumab, the only approved therapy for PNH. 1 The study also showed that nearly all patients on eculizumab have reticulocytosis with an average of 1.9x the upper limit of normal (ULN).  In our PADDOCK study, patients achieved transfusion independence with an average hemoglobin increase of 4.2 g/dL by day 85 to 12.2 g/dL and average reticulocytes decrease of 50% from 2.0x ULN to 1.0x ULN. LDH was reduced from 9.7x ULN at baseline to 0.9x at day 85 with 80% of patients achieving normal LDH. We could not be happier with these results as they show APL-2 represents a promising potential improvement in treatment options for PNH patients.”
These data will be presented by Dr. Raymond SM Wong of the Department of Medicine & Therapeutics, Prince of Wales Hospital at The Chinese University of Hong Kong. Professor Wong is a principal investigator for the PADDOCK study.
“APL-2 shows meaningful improvement in hematological parameters in ways not seen with standard of care C5 inhibition,” said Dr. Raymond Wong. “The hemoglobin increases and transfusion avoidance are highly meaningful, as is the broader hematological correction, including reticulocytes and bilirubin. The safety is also promising and the subcutaneous route of administration is friendlier to patients.”

Becoming an initiator


With the year coming to a close, I’ve spent intensive time at a number of trading and investment firms helping money managers maximize their 2018 performance. Interestingly, one set of questions has stood above all others in the recent meetings:  How can I evaluate the positioning in an asset class or stock? What is the sentiment about the market? How crowded is this trade? Underlying these questions is the notion that the herd  of market participants generally produces subnormal returns. If we can figure out what the herd is doing, we can position ourselves to benefit from their follies or, at the very least, act on our own views when those are least crowded.
My distinct observation has been that the people most likely to ask these questions are those with views and market exposures similar to others. Managers trading highly idiosyncratic strategies and markets don’t really think about the herd. Their processes are sufficiently unique that they don’t have to worry about the actions of others. Those most concerned seem uneasy perhaps because they sense that they are operating in a crowded space.
The social psychologist Robert Cialdini offers a provocative generalization: 95% of people are imitators and only 5% are initiators. By definition, imitators are those so influenced by others that they rarely initiate their own ideas and actions. Team Cialdini cites a fascinating Scientific American report from Krystal D’Costa regarding why people don’t return their shopping carts to the designated areas. It turns out that some people are regular returners and others are not, but most of us are influenced by the return behavior of those preceding us. If the lot is littered with stray carts, we are more likely to abandon our cart. A neat lot is more likely to lead us to return our cart and preserve neatness. What’s more, when people have circulars left on their windshields, they are more likely to throw those on the ground and litter when the car is in a lot with stray carts. A neat lot leads to less littering. D’Costa explains, “…as a situation broaches on deviance, more people will trend toward disorder; once we have permission to pursue an alternative action, we will do so if it suits us.”
In other words, we are easily influenced by factors outside of our awareness. That makes us imitators, not initiators.
At the trading firm SMB, Mike Bellafiore introduced a concept called “the playbook.” The idea is drawn from sports teams: just as a coach has a collection of plays to run on a football or basketball team, a trader can create a collection of “setups”–observable patterns of supply and demand–that guide buying and selling decisions. The playbook concept is interesting because it pushes traders to be initiators. Developing traders discover the patterns that make sense to them and translate those into favorable reward-to-risk opportunities. Indeed, every trader on the SMB desk has their playbook.
In spite of that, it is not unusual for traders on the floor to be trading the same exact stocks in the same direction. Once a “stock in play” hits the radar for experienced, successful traders, it is likely to be followed by many developing traders. To be sure, some of this following reflects useful mentoring. Even in mentoring situations, however, one would expect each trader to trade the opportunity his or her own way. For many traders, that is not the case. Despite researching “initiator” patterns, they act as “imitators”.
In the past several weeks, I initiated conversations with three of the most successful traders at the firm. All are doing much better than they had the year before, and all are solid seven-figure earners with superior risk-adjusted returns. To a person, they are making money doing things they hadn’t done the year before. For example, some are trading different time frames; some are making greater use of options; some have expanded the universe of what they trade. Their success stemmed from being initiators: they followed a fresh path that was not one others were seeking.
So how can we become better at initiating? D’Costa’s work suggests that an important step is to remove ourselves from surroundings that influence us. Much of our vulnerability to the herd, Cialdini has found, is not due to direct persuasion but to “pre-suasion”: our prior exposure to situations and settings that nudge us in particular directions. Our physical and interpersonal settings help shape our thoughts and decisions.
Over the years, I have been struck by the degree to which successful portfolio managers have sought solitude as part of their trading processes. Some retire to separate office space to conduct their research; some engage in meditation on a routine basis; some wear headphones while on the trading floor. I once asked a manager what he was listening to while on the floor. He smiled and said, “Nothing!”. It turned out that the headphones were of the noise-cancelling variety and created an influence-free zone for his decision-making. In her book, Susan Cain cites “quiet” as a key element in “the power of introverts.” It is precisely their immersion in their own processing that enables them to be creative initiators of ideas. Too often, she notes, it is the noise of collaboration that kills creativity.
One very talented quantitative money manager, a great example of Cain’s introverts, also wore headphones in his office.  It turns out he used them to immerse himself in beautiful classical music. It was “pre-suasion” at its best, a priming to filter out the noise of office politics and emails, and create a mind space receptive to the appreciation of complexity. That money manager has been a consistent innovator in both academic and investment arenas.
In a world of smart phones, non-stop chats, and social media postings, quiet and solitude are difficult to come by. Yet those are precisely the factors that may help us become creative initiators and effective leaders. Our settings influence our performance every bit as much as our “playbooks”. With focused quiet, we are most likely to find our own paths.

Aslan Pharmaceuticals presents positive data from Phase 2a leukemia study at ASH


ASLAN Pharmaceuticals announced the presentation of new positive data from the ongoing phase 2a study of ASLAN003 for the treatment of acute myeloid leukaemia at the 60th American Society of Hematology Annual Meeting. ASLAN003 is an orally active, potent inhibitor of dihydroorotate dehydrogenase that has the potential to be first-in-class in AML. As of 16 November 2018, 14 patients with AML ineligible for standard treatment had been enrolled in the multicentre dose optimisation study to evaluate ASLAN003 monotherapy administered as a 28-day cycle. Eight patients had received at least one post-treatment assessment at the cut-off date and were evaluable for efficacy. Of the 8 evaluable patients, 4 patients showed clinical signs of efficacy: 2 patients exhibited evidence of myeloid differentiation and 1 patient in the 100mg QD cohort developed suspected differentiation syndrome. Overall, 4 patients had stable disease for more than 3 months. ASLAN003 has been well tolerated in patients treated to date. The most commonly occurring related adverse events were leukocytosis, nausea and rash, with grade 3/4 leukocytosis in 1 patient. The study contains 4 cohorts for the optimum dose determination, and an additional expansion cohort with the selected optimum dose. The primary outcome of the phase 2a study is to determine the optimum monotherapy dose of ASLAN003 and provide a preliminary estimate of efficacy evaluated by overall complete remission rate. A phase 1 trial showed that ASLAN003 demonstrated dose proportional pharmacokinetics and was safe and well tolerated in healthy volunteers compared to the side effect profiles of existing AML induction and maintenance chemotherapies. ASLAN003 has demonstrated potent inhibition of DHODH, lack of toxicities associated with first generation inhibitors and other novel AML therapies, and the potential to induce differentiation in blast cells and applicability in a broad range of AML patients. The US Food and Drug Administration has granted ASLAN003 Orphan Drug Designation as a treatment for AML. ASLAN will also present new data from a preclinical study evaluating the effects of ASLAN003 on cell growth, differentiation, apoptosis, and gene expression changes in AML cell lines and primary bone marrow cells from patients with AML.
https://thefly.com/landingPageNews.php?id=2830807

MEI Pharma presents data from ongoing Phase 1b Lymphoma Study

MEI Pharma announced that results from an ongoing Phase 1b study support the complementary potential of intermittent and continuous dosing schedules of ME-401, a selective phosphatidylinositol 3-kinase delta inhibitor, to optimize the clinical risk-benefit ratio in patients with relapsed/refractory follicular lymphoma. The data demonstrate that ME-401, as both a single agent and in combination with rituximab, continues to be associated with overall high objective response rates. In addition, low rates of Grade 3 immune-related adverse events were observed in patients on the intermittent dosing schedule while maintaining a high level of clinical response. The data announced at ASH continues to support the rationale for MEI’s planned Phase 2 study that evaluates both a continuous and intermittent dosing schedule of ME-401 as a means to enhance the drug candidate’s clinical profile and thus potentially deliver improved benefits to patients. The Phase 2 study is expected to start around year-end and is intended to support MEI’s accelerated approval registration strategy if successful. Patients in the Phase 1b study received ME-401 as a single agent and in combination with rituximab to explore treatment options for patients with B-cell malignancies. The IS dosing regimen consists of 60 mg given continuously, once-daily, for the first 2 cycles followed by 60 mg given on days 1-7 of a 28-day cycle and results showed: As a single agent, 76% objective response rate in patients with relapsed or refractory follicular lymphoma, and 100% in all patients with chronic lymphocytic lymphoma and small lymphocytic lymphoma. In combination with rituximab, 78% objective response rate in patients with FL. Median duration of response has not been reached. The lead patient has a duration of response of approximately 20 months and the median follow-up is 9.3 months. Low rate of irAEs; 4 irAEs were reported in 36 patients administered the IS, with all cases occurring in the first 2 cycles following the switch to IS. 89% of patients switched to IS remain on therapy. Disease control was maintained in 72% of these patients. 70% of patients who resumed on the continuous daily dosing schedule recaptured a response after progressing on IS.
https://thefly.com/landingPageNews.php?id=2830809

Blockchain firm Witty Health launches digital cancer decision tool


The health blockchain technology firm Witty Health has launched OncoPower, a digital tool helping oncologists with their decision making.
OncoPower helps oncologists create a de-identified case study with details like co-morbidity, specific cancer type, lines of therapy, and actual drugs used for treatment.
It then rates the effectiveness of those drugs and publishes the data on the fly in minutes.
The purpose of the tool is to assess if drugs safely and effectively improve a patient’s health status with a specific cancer and stage.
A Peer Compare tool enables community oncologists to compare their proposed treatment plans with their peer’s practice preferences as more data is gathered.
Several variables can be changed including gender, age, comorbidity, primary cancer site, specific cancer, stage, lines of therapy, prior treatment, and drug.
The tool will be funded by a blockchain-generated digitally generated security called Onco, which the company describes as “the fuel of the incentivised oncology market”.
Participants in OncoPower will invest in “Oncos”, which is distributed using transparent consensus algorithms.
Witty Health co-Founder and chief oncologist, Karthik Koduru, said: “As we continue to advance the development of OncoPower digital health ecosystem, we are pleased to enable oncology providers to publish their specific case studies and rate the effectiveness of drugs benefiting everyone– patients, oncologists, drug discoverers, and pharmacists in the cancer care value chain.”
“The OncoPower drug rating differs from other methods used to rate drugs because it is based on their use in a real world clinical case. This drug rating aims to improve efficiency, delivery of care, and outcomes by providing patient specific and data-driven smart treatment options to Oncologists.”
Dr Amitkumar Mehta, a medical oncologist and hematologist at the University of Alabama School of Medicine in Birmingham, said: “The best part of the OncoPower platform is that its development is completely ground up with direct inputs from the practicing oncologists, who see several hundred cancer patients every month and it is led by a team of Oncologists who know what is best for the patients.”

Healios begins trials of mental health app for schoolchildren


Digital health firm Healios is beginning clinical trials of ThinkNinja, an app designed to help children with mental health problems.
ThinkNinja is aimed at helping young people aged 11 to 17 years old with their mental health, emotional wellbeing and resilience, and supports symptoms of anxiety and low mood.
The product is the first in a series in development from Healios, and aims to provide instant access to high-quality, early intervention care for young people, especially for those who are struggling with their mood.
The trial will test ThinkNinja with 5,000 school children across schools in Madrid, Devon, Hampshire, Somerset and Derbyshire.
Healios said ThinkNinja has been built by technical, design, and clinical experts, guided by young people.
The app uses a learning algorithm to develop a deeper understanding of the user, through asking a series of clinically related questions.
It is designed as an early intervention to help with the stresses that life throws at all teenagers, from exams to relationships and dealing with social interactions.
ThinkNinja can pick up on behaviours that fuel anxiety and low mood and then help the user develop new behaviours and coping strategies to face their fears.
If the young person’s mental health worsens, the app will also detect risky behaviours such as suicidal thinking and support the young person to reach out for urgent help.
ThinkNinja was not designed to replace human clinicians but to help young people manage and cope better.
But the hope is that the app will help reduce the burden on schools and NHS mental health services.
Richard Andrews, founder and CEO of Healios, said: “With the app’s artificial intelligence engine, it automatically adjusts to support the young person with evidence based clinical techniques if they have developed symptoms of anxiety or low mood. With its learning algorithms, 24/7 accessibility and gamification appeal, ThinkNinja is designed especially for today’s digital-native generation.”
Ms Helen McKay, senior assistant headteacher at St Mary’s Catholic High School in Chesterfield, Derbyshire said: “ThinkNinja is an exciting innovation from Healios and one that complements our existing wellbeing support services to help increase access to evidence-based interventions required by young people through a channel that we know they love to engage through. We’re thrilled to be part of the clinical study to pilot this new app.”

NICE approves Bayer’s liver cancer drug


NICE has given Bayer’s advanced liver cancer therapy Stivarga (regorafenib) the go-ahead after it undertook a rapid review following earlier guidance that rejected the drug.
The medicine is for adults in England and Wales whose liver is well functioning but unable to be surgically removed and who have already taken Bayer’s life extending medicine Nexavar (sorafenib).
In March this year, the National Institute for Health and Care Excellence (NICE) found that regorafenib was less cost-effective than treatments it usually considers are an acceptable use of resources for end-of-life care.
But it reversed its decision after a new commercial arrangement made regorafenib available to the NHS at a confidential, lower price.
Regorafenib is an oral multi-kinase inhibitor that blocks multiple protein kinases involved in tumour angiogenesis. It slows down the growth and spread of cancer cells by cutting off their blood supply.
Clinical evidence demonstrated that those treated with sorafenib, and who have good performance status and less severe liver impairment, live longer with regorafenib than patients having supportive care.
There was an overall survival (OS) of 2.8 months compared to placebo – 10.6 months versus 7.8 months.
Meindert Boysen, director for the NICE Centre for Health Technology Evaluation, said: “Regorafenib is an important treatment option to extend the lives of people with previously treated advanced hepatocellular carcinoma after they’ve already been prescribed sorafenib.
“We are pleased that the company has responded by seeking a rapid review of our original guidance and offered a price that allows us to conclude that the drug is cost-effective for routine use on the NHS in England and Wales.”
This is hopeful news for patients, especially as around 15 people are diagnosed with liver cancer every day, according to the British Liver Trust.
Judi Rhys, chief executive of the British Liver Trust, said: “Hepatocellular carcinoma (HCC) is the most common form of liver cancer. It is particularly aggressive with the five-year survival rate being on average only 12% and a diagnosis is therefore devastating for the patient and their families.
“Access to the drug will potentially provide patients with valuable extra time with their loved ones.”
Earlier this month, the European Commission approved Ipsen’s Cabometyx(cabozantinib) as a second line therapy for patients who had been treated with Nexavar.
Cabometyx can be used as a second line monotherapy for hepatocellular carcinoma, giving patients another treatment option, as the only medicine previously available after Nexavar was Stivarga.