Assembling my biofolio...
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BPMC/(Deciphera)
Re: GNRO
GNRO - initial P2B data CC notes
1. Company pointed out several possibilities for failure of the first part of the MS trial, including:
A. Drug may not have had time to reach therapeutic concentrations in the brain and have impact. Based on previous studies, PK steady-state in serum isn't reached until 5 months of treatment.
B. Could take longer than expected for immune system to react to neutralization of a pathogenic protein. In comparison to existing disease modifying treatments which have immediate and direct immune-modulation or immune suppression effect, don't know time course of potential benefit of neutralizing a potential causal factor of autoimmunity. Company gave analogy of if refinery is on fire, cutting off supply of fuel may not immediately stop the fire and it may take time to see an effect.
C. In P2A trial, it took 6 months to have pharmacodynamic effect in reducing expression of pathogenic protein mRNA in peripheral blood mononuclear cells.
D. May not have got enough antibody into the brain. They were able to do a number of spinal taps in this study but the data is not yet available.
2. Don't believe the initial MS failure has read-through to the ongoing P1B type-1 diabetes trial as there the drug would be targeting the pancreas as opposed to having to cross the BBB for MS.
GNRO - initial P2B MS data flops
[Shares ended up down ~65% on this data. I gave serious consideration to a small position in front of this data but, fortunately, decided it was best to wait for this data since the entire premise of the company is based on the theory of targeting retroviruses for MS and other disease indications.]
http://www.geneuro.ch/data/news/geneuro-pr-6m-results-eng-3.pdf
GeNeuro and Servier Announce Six-Month Results from CHANGE-MS Phase 2b Study in Multiple Sclerosis
? GNbAC1 is well tolerated
? Anti-inflammatory effect not demonstrated at 6 months
? Analysis of full 12-month Phase 2b data expected 1Q18
? Telephone conference in English on Monday August 28 at 2pm (CET) / 8am (EDT)
Geneva, Switzerland, and Paris, France, 28 August 2017 – 07:30am CEST – GeNeuro (Euronext Paris: CH0308403085 – GNRO) and Servier announced today 6-month results from the 12-month CHANGE-MS Phase 2b study of three doses of GNbAC1 for the treatment of patients with relapsing- remitting multiple sclerosis (RRMS). The data showed that GNbAC1 is well tolerated and that there is no statistical difference at 6-months between GNbAC1 and placebo in the study’s primary endpoint of reducing the number of cerebral Gad-enhancing lesions as measured by MRI, nor on the other MRI measures of neuroinflammation. Relapses in the overall population decreased by over 50% relative to the year prior to study but there was no significant difference at 6 months between treated and placebo groups. Based on the unique mechanism of action and pharmacokinetics of GNbAC1, the study will continue, as planned, exploring potential benefits of the drug on MRI and clinical measures, including remyelination properties, with final results from the full 12-month expected in the first quarter of 2018.
CHANGE-MS Phase 2b study is a randomized, double-blind, placebo-controlled study of 270 RRMS patients in 50 clinical centers in 12 European countries. The primary endpoint at 6 months is an assessment of the efficacy of GNbAC1 based on the number of inflammatory lesions on brain MRI. Secondary endpoints at 12 months will also include MRI measures of neurodegeneration, clinical parameters, and biomarkers, including pathogenic pHERV-W env. The protein could be a causal factor in the development of multiple sclerosis.
“CHANGE-MS being a study evaluating an innovative approach not immunosuppressive in MS, a longer delay of action than seen with other drugs is possible. The 6-month data showed a good safety profile. From a clinical perspective, it is important to wait for the full 12-month results,” noted Prof Hans-Peter Hartung, chairman of the Department of Neurology of the University Hospital Düsseldorf and principal investigator of the CHANGE-MS study.
“In line with Servier’s commitment to bringing new safe and effective treatments to patients, we will continue working with GeNeuro to better understand the potential clinical benefits of this innovative drug, GNbAC1, and wait for the full results of the study at 12 months,” added Dr. Christian de Bodinat, Director of Servier’s Neuro-psychiatry Therapeutic Innovation Pole.
“GNbAC1 is a new way to treat MS patients, with a novel mode of action. Analysis of the data is ongoing to better understand potential therapeutic benefits,” stated Jesús Martin-Garcia, CEO of GeNeuro. “We are fully committed to this technology and look forward to final results from this 12- month study, expected in the first quarter of 2018.”
GNbAC1 is a monoclonal antibody which aims at neutralizing a retroviral pathogenic envelope protein (pHERV-W env) encoded by a member of the HERV-W family. Human endogenous retroviruses (HERVs) are ancestral retroviral DNA insertions in the human genome, thought to account for up to 8% of the human genome. The pHERV-W env protein is thought to be a causal factor in the
development of multiple sclerosis and Type 1 diabetes. GeNeuro is currently conducting a Phase 2a study in Type 1 diabetes, with results expected during the third quarter of 2018.
Conference call:
Jesús Martin-Garcia, Chairman and CEO, and the company management will present during a conference call in English, on Monday, August 28, 2017 at 02:00pm CEST / 08:00am EDT followed by a Q&A session.
To access the call, please dial the following teleconferencing number:
+33 (0) 1 72 00 15 10 / PIN code: 95777396#
Following the live call, a replay will be available on the GeNeuro website: www.geneuro.com
GLPG/FGEN/IPF -
Re: GLPG P2 IPF data CC slides
So, my FGEN bias notwithstanding, there were several others (h/t @sport234a @subset_member @bio_clouseau) that today posted on Twitter some fairly bearish takes on the P2 GLPG IPF data based on the CC slides. In addition to the very small patient numbers and limited 12-week duration of data, other points included:
1. The FVC data is not based on the intent-to-treat (ITT) population. How would the data change if data on full ITT population was reported?
2. Slide 13 shows change in FVC over time but there are varying numbers of patients reported at differing time points. E.g., at week 4 data is shown for 3 placebo patients but then at the week 8 point data is for some reason shown based on 4 placebo patients. Why was the fourth patient on placebo not included in the data at the week 4 point and how would that change the totality of the data if included there? Also, why were 3 placebo patients (out of only 6 total) removed from the data set at some point between baseline and week 4?
3. The placebo actually appears to outperform the drug from week 4 to week 12 and from week 4 to follow-up.
All told, I certainly can't entirely dismiss the GLPG IPF threat to FGEN, but I also don't feel as concerned about this potential competitive threat as I did upon reading the initial PR.
FGEN -
FGEN -
Cosmo (COPN) - submits LuMeBlue NDA
http://www.cosmopharma.com/news-and-media/press-releases-and-company-news/2017/170724
Dublin – July 24, 2017 – Cosmo Pharmaceuticals N.V. (SIX: COPN) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking marketing approval for LuMeBlue® (methylene blue), its drug aimed at enhancing the detection rate of adenomas.
LuMeBlue® Results
In the trial LuMeBlue® was compared to Standard of Care (“WLHD”: White Light colonoscopy with High Definition endoscopes). The primary endpoint in the phase III trial was the number of subjects with at least one histologically proven adenoma or carcinoma.
LuMeBlue® attained the primary endpoint identifying 17.71% more patients with adenomas or carcinomas than WLHD (p value 0.009; Relative Risk-RR-1.177). Adenomas were found in 56.3% of all subjects when using LuMeBlue®, whereas WLHD found adenomas in 47.8% of all subjects. LuMeBlue® therefore proves very efficient in flagging lesions.
In the phase III clinical trial the false positive rate (an important secondary endpoint) in the LuMeBlue® arm was lower than in the WLHD. In the LuMeBlue® arm 356 subjects out of 485 subjects had an excision. 83 of these subjects (23.3%) were false positives. In the WLHD arm 326 out of 479 subjects had an excision and 97 of these subjects (29.7%) were false positives. Thus LuMeBlue® finds more subject with lesions than WLHD, which subsequently prove to be more adenomas or carcinomas.
LuMeBlue® was also statistically superior and clinically very meaningful in the segment of subjects with 0-3 excisions, where 75%-80% of the patients are. In the segment of 0-3 excisions covering 362 subjects, the LuMeBlue® Adenoma Detection Rate (ADR) was 45.3%, while the ADR covering 376 subjects using WLHD was 35.9% (p value 0.0107). This is an improvement of 26.2% (RR 1.262).
There were no reported major drug related adverse events.
LuMeBlue® trial design
The LuMeBlue® trial was conducted in 18 leading centers in 8 countries in North America and Europe. The Intention to Treat Population (ITT) was 1,249 subjects, the Full Analysis Set (FAS) was 1,205 subjects, the Per Protocol Set (PP) was 1,137 subjects and the safety set was 1,208 subjects. As agreed with the Regulatory Agencies, the endpoints were set according to FAS.
Four Clinical Research Organisations (CROs) were used: One CRO was responsible for the monitoring activities, one for the electronic CRFs, one for the bio-statistical activities and one for the high definition video recording activities and storing.
Two central histolabs, one each in the EU and one in the USA, were responsible for the histologic analysis of the excised tissues, 5 endoscopy centers, 2 in North America and 3 in Europe, were randomly assigned videos for review, and there was one endoscopy charter and one histology charter.
Subject population
In the FAS 479 subjects were treated in the WLHD arm of which 61.6% were males; 47,8% were first-time screening colonoscopies, 6,3% were surveillance colonoscopies performed less than two years since the last colonoscopy and 45,9% were surveillance colonoscopies performed after more than 2 years following the first-time colonoscopy.
485 subjects were in the LuMeBlue® arm of which 60.6% were males, 48% were first time screening colonoscopies, 5.8% were surveillance colonoscopies performed less than two years since the last colonoscopy and 46.2% were surveillance colonoscopies performed after more than 2 years following the first-time colonoscopy.
241 subjects were treated in the confounding arm (not statistically powered).
About Cosmo Pharmaceuticals
Cosmo is a specialty pharmaceutical company that aims to become a global leader in the field of optimized therapies for selected Gastrointestinal Disorders and Endoscopic Procedures. The Company’s proprietary clinical development pipeline specifically addresses innovative treatments for IBD, such as Ulcerative Colitis and Crohn’s Disease, and Colon Infections. In addition, the Company has developed a medical device for polyp and adenoma excision and is has filed the NDA for LuMeBlue™, a diagnostic drug for the detection of colon cancer as well as new chemical entities that are being developed by the associate company Cassiopea S.p.A. for the topical treatment of skin diseases. Cosmo’s MMX® products that have reached the market are Lialda®/Mezavant®/Mesavancol®, a treatment for IBD that is licensed globally to Giuliani and Shire Limited and Uceris®, the first glucocorticosteroid indicated for the induction of remission in active, mild to moderate Ulcerative Colitis, licensed in US to Santarus/Salix/Valeant and in the Rest of the World to Ferring as Cortiment®. Cosmo’s proprietary MMX® technology is at the core of the Company’s product pipeline and was developed from its expertise in formulating and manufacturing gastrointestinal drugs for international clients at its GMP (Good Manufacturing Practice) facilities in Lainate, Italy. The technology is designed to deliver active ingredients in a targeted manner in the colon. For further information on Cosmo, please visit the Company’s website: www.cosmopharma.com
Alzheimer's NYT piece - Ancient Cure?
https://www.nytimes.com/2017/07/14/opinion/sunday/alzheimers-cure-south-america.html
An Ancient Cure for Alzheimer’s?
Pagan Kennedy JULY 14, 2017
In 2011, Ben Trumble emerged from the Bolivian jungle with a backpack containing hundreds of vials of saliva. He had spent six weeks following indigenous men as they tramped through the wilderness, shooting arrows at wild pigs. The men belonged to the Tsimane people, who live as our ancestors did thousands of years ago — hunting, foraging and farming small plots of land. Dr. Trumble had asked the men to spit into vials a few times a day so that he could map their testosterone levels. In return, he carried their kills and helped them field-dress their meat — a sort of roadie to the hunters.
Dr. Trumble wanted to find out whether the hunters who successfully shot an animal would be rewarded with a spike in testosterone. (They were.) As a researcher with the Tsimane Health and Life History Project, he had joined a long-running investigation into human well-being and aging in the absence of industrialization. That day when he left the jungle, he stumbled across a new and more urgent question about human health. He dropped his backpack, called his mom and heard some terrible news: His 64-year-old uncle had learned he had dementia, probably Alzheimer’s.
In just a few short years, his uncle, a vibrant former lawyer, would stop speaking, stop eating and die. “I couldn’t help my uncle,” Dr. Trumble said, but he was driven to understand the disease that killed him. He wondered: Do the Tsimane suffer from Alzheimer’s disease like we do? And if not, what can we learn from them about treating or preventing dementia?
“There is really no cure yet for Alzheimer’s,” Dr. Trumble told me. “We have nothing that can undo the damage already done.” Why, he wondered, had billions of dollars and decades of research yielded so little? Perhaps major clues were being missed.
Dr. Trumble was trained as an anthropologist, and his field — evolutionary medicine — taught him to see our surroundings as a blip in the timeline of human history. He thinks it’s a problem that medical research focuses almost exclusively on “people who live in cities like New York or L.A.” Scientists often refer to these places as “Weird” — Western, educated, industrialized, rich and democratic — and point out that our bodies are still designed for the not-Weird environment in which our species evolved. Yet we know almost nothing about how dementia affected humans during the 50,000 years before developments like antibiotics and mechanized farming. Studying the Tsimane, Dr. Trumble believes, could shed light on this modern plague.
The Tsimane suffer from high infant-mortality rates, but those who reach adulthood live about as long as most other people, making it possible to measure their health outcomes up to age 90 and beyond. The Tsimane Project researchers have spent more than 15 years following their volunteers and providing medical treatment. They’ve found that Tsimane differ from the rest of us in many ways. For example, they have the cleanest arteries of any population that has ever been studied, meaning that they may be largely immune to heart disease.
Dr. Trumble was not the first member of the Tsimane Project to wonder about dementia in this population. In 2002, one of the group’s founders, Michael Gurven, began testing mental fitness by asking older people to do puzzles. This and other cognitive-performance data piled up until 2015 — the year that Dr. Trumble’s uncle died. That was when Dr. Trumble, Dr. Gurven and other researchers decided to dive into it.
Dr. Trumble was particularly interested in the ApoE4 gene, often called the Alzheimer’s gene. Americans who carry two copies of the gene are more than 10 times as likely to develop the late-onset form of the disease. Dr. Trumble found something startling when he looked into the Tsimane data: Many of those with a copy of the gene seemed to perform better on the cognitive tests.
He mulled this paradox in his sunny lab back at Arizona State University. He had just returned from another trip to the Tsimane settlements, and a bit of Bolivia had come with him: an intestinal infection from the campylobacter bacteria and two nasty species of E. coli. “I got so sick that I almost missed my wedding,” he said. This was not his first encounter with tropical parasites. Years before he had noticed what looked like a zit on his nose. When it kept growing, he realized it was a flesh-eating parasite called leishmania. Chemotherapy saved his nose, and perhaps his life.
“Getting parasitic infections gave me perspective,” he said. At least 70 percent of the Tsimanes are infected with parasites — worms in their guts, invaders burrowing into their skin — at any given time. The same was likely true of our ancestors. He began to wonder: Could these infections change the way that genes affect our bodies?
Perhaps the ApoE4 gene provided a survival advantage in ancient environments. Today only about a quarter of us have a single copy of the ApoE4 gene, and only about two in a hundred carry a double dose. But DNA analysis of ancient bones shows that thousands of years ago, the ApoE4 genotype was ubiquitous in humans. The gene — which helps to generate cholesterol — might have been a crucial step in the development of our big, energy-hungry brains, and it may have played a key role in defending those brains from pathogenic invaders.
Dr. Trumble then looked at the data on the cognitive health of all the Tsimane volunteers who had tested positive for parasites. Sure enough, he found that Tsimane with infections were more likely to maintain their mental fitness if they carried one or two copies of the ApoE4 gene; for them, the “Alzheimer’s gene” provided an advantage. For the minority who’d managed to elude parasitic infection, however, the opposite was true, and the ApoE4 gene was connected with cognitive decline, just as it is for people in industrialized countries.
“Humans co-evolved with a number of different parasites, but today, in our sedentary city life, we’ve removed those parasites from the mix,” Dr. Trumble said. This could be what transformed the gene from an advantage into a liability.
As it happens, these findings dovetail with some new research from university labs. In papers released in 2016 and 2017, scientists looked at dementia in a new way — not just as a disease that results from the gradual breakdown of our cells, but as a disorder in which the brain turns against itself.
Years ago, while reporting a story about the Harvard Brain Tissue Resource Center, I had a chance to peer through a microscope at a slice of brain collected from a patient who’d died of Alzheimer’s disease. The tissue was pocked with amyloid plaques that resembled black clouds. I also spied the tau tangles that look like hair clogging a drain and are characteristic of Alzheimer’s pathology.
For decades, most researchers have agreed that these plaques and tangles are the key malefactors of dementia, and that if you could clear them from the brains of patients, you would halt or reverse illness. Researchers have been especially focused on finding a drug that could erase amyloid plaques, and we now have dozens of compounds that do that in mice.
But this approach has led to failure in humans. Even when drugs can clear the plaques in patients’ brains, the disease continues to wreak damage.
Now some scientists believe that the focus on amyloid plaques might have been a mistake. Instead of looking at what goes wrong, they’re trying to understand what goes right.
Changiz Geula, a professor of neuroscience at Northwestern University, has been studying brain tissue collected from people who died at age 90 or older. He found that some people who die with sharp minds have brains that are clogged with the gunk associated with Alzheimer’s pathology. That means it’s possible to have an “Alzheimer’s brain” but no dementia. Dr. Geula believes that in cases like this, some actor in the brain — call it the opposite of Alzheimer’s — is protecting neurons from damage. We still don’t know what it is.
One candidate might be the astrocytes, cells that support the neurons and synapses, keeping them healthy even in the presence of plaques and tangles. In a 2017 paper in Nature, Stanford University researchers described how these usually peaceable cells can flip into a “killer mode,” becoming assassins that spew out toxins and destroy the very cells they once nursed.
According to Shane Liddelow, one of the authors of the paper, this Jekyll-and-Hyde personality of the astrocytes likely developed thousands of years ago to fend off the infections that invaded the brains of our ancestors. At the first sign of trouble, the astrocytes go on the attack, destroying everything in their path — including sometimes healthy brain tissue. Neurons can become “innocent bystanders in this protective killing effort,” Dr. Liddelow explained.
Nowadays, since most of us live in more sterile environments, this army in our brain is no longer busy fighting pathogens, and so it responds instead — often far too vigorously — to the amyloid plaques and tangles that are a part of normal aging.
“Ten years ago, very few scientists were looking at whether the immune system was related to Alzheimer’s, but that question has just exploded,” Dr. Liddelow said. “At every scientific meeting I’m at, everyone’s talking about this question: Why are some people with lots of amyloid plaques — the people who, according to our models, should get Alzheimer’s — protected from this runaway immune response? I think the answer will come from looking at immune cells of humans around the world living in different environments.”
I asked Dr. Liddelow whether he was familiar with the Tsimane research. He admitted that he was not — the field of evolutionary biology is distant from his own. But he said the hypothesis that the ApoE4 gene evolved to protect our brains from the effects of parasitic infection made perfect sense. “That’s absolutely in line with what we found. For our ancestors, an ApoE4 gene could have been beneficial,” Dr. Liddelow said, in part because it would have helped the astrocytes go on the attack.
Dr. Liddelow, who just took a job as assistant professor at New York University, is now setting up his own lab to test out that theory. He believes that this new focus will lead to “a rapid production of effective treatments.”
Dr. Trumble has hopes that his work will eventually lead to treatments as well. These days cancer scientists are brewing up designer viruses that help the body attack tumors. Why not designer parasites?
Soon after I first interviewed Dr. Trumble, he mailed some of his own saliva to a testing service to find out whether he had the ApoE4 genotype. Recently he received an answer: He carries one copy of the ApoE4 gene. For most Americans, that would mean an elevated risk of Alzheimer’s disease. Of course, Dr. Trumble — who still spends months each year sleeping in a tent, eating wild meat and drinking river water — is no ordinary American.
I asked whether he thought his past infections had inoculated him against damage in his brain.
“I don’t know,” he said. “I’m definitely not going to run out and infect myself with more parasites, since the science isn’t there yet” to show that these infections could be used as a therapeutic. “I definitely don’t want people to read this and go out and try to infect themselves,” he added. “Parasites can be very unpleasant or dangerous in their own right.”
But, he said, “I certainly hope, before I get to age 80, we are able to figure out the mechanism” behind a pathogenic therapy.
Perhaps that would mean a drug for people who carry the ApoE4 gene, one that would mimic the effects of a parasite without incurring the damage of an infection — a kind of muzzle for the brain’s immune system that would keep cells like the astrocytes from attacking healthy neurons.
Still, Dr. Trumble and the rest of the research team will need to gather more data before they can answer even the most basic questions: What is the rate of dementia in the Tsimane population? Are certain parasites more beneficial to the brain while others are harmful? And which humans are the most likely to receive a cognitive benefit from infection?
If the Tsimane do hold the keys to a cure, Dr. Trumble and his colleagues have no time to waste. “We have researchers in the field right now collecting data,” he told me. “They’re way upriver,” in a settlement far off the grid. Yet Dr. Trumble gets frequent updates: He uses Skype to call into the Bolivian field office, where a radio relays crackly messages from his colleagues in the jungle. This jerry-built system has sped up the research process, but it also presages a time in which the Tsimane Project’s mission will need to change.
Cellphones, canned food and other artifacts of modern life are seeping into the Tsimane communities. “This may be our last chance to understand whether chronic conditions of aging like Alzheimer’s and cardiovascular disease have always impacted humanity, or whether they’re connected with industrialization,” Dr. Trumble said.
The Tsimane, he fears, are becoming weird like us.
BOLD - AT307 for CPVT
Just because I like to bounce cardio stuff off of you, have you looked at the recently public BOLD's GT approach to treat Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)? They are specifically targeting CASQ2-related CPVT and trying to achieve long-term expression of calsequestrin 2 in cardiac muscle cells. They claim that by restoring CASQ2 protein levels, the heart is able to maintain a normal heartbeat rhythm. See: http://www.audentestx.com/at307/ .
GKTX -
KMPH -
KMPH -
KMPH - ADHD update CC
Just to update the prior post, I listened closely to the ADHD update CC referenced in the PR and they effectively state that KP415 has an effective duration through about 13 hours with onset of efficacy at about 30 minutes. At best, most methylphenidate ADHD drugs have a duration of effect around 10 hours (no reference to how quickly they begin to work).
KMPH - new ADHD candidate
[I only recently became aware of this company even though they've now been public a few years. And I fully admit ADHD is not my space at all. They claim that the CEO/co-founder was the principal inventor of Vyvanse so, assuming true, that may bode well for their push into ADHD. Also, the stock is way off its highs given the issues they have encountered in the pain space to date. Looks like EV may be around $80M given current market cap around $60M and $72M in cash as of 3/31/17 plus about $90M in LT (2021) convertible notes (would look a lot more attractive if didn't have that big LT note liability).
Key comments/questions for you and others:
(1) Seems like we should take the company assertion at face value that KP415 is the key asset to focus on, and not KP484, as that is the one they call their highest value product candidate in the PR below.
(2) They cite the strengths of KP415 as being the early on-set of action and better total duration. Slide 9 of the supporting slides to the related call for this PR indicate that more prescribers view the duration of action as the key advantage over the abuse potential and early onset of action.
(3) In slide 5 of the supporting slides, they compare the oral PK data of KP415 solely to that of Concerta. Are there any red flags in comparing solely to Concerta and not also to, say, Vyvanse? Also, assuming that comparison is okay, is it meaningful if the drug ends up definitively showing in the clinic (as it does in the P1 data shown in the slides) significantly higher PK concentration out to about 6 hours where it then is roughly comparable to Concerta until you get out past 16 hours through to 24 hours where KP415 does then diverge again from Concerta? At hour 24, Concerta PK data is near 0 whereas KP415 is still at about 2-3 ng/mL.
(4) Is it likely that KP415 will need more than just these possible duration of action or early onset of action advantages and will also need to get some type of abuse deterrent component on the ultimate label (where they had issues with FDA with prior pain drug)?]
KemPharm Strengthens ADHD Prodrug Pipeline with Development of KP484, A New, Super-Extended Release ADHD Methylphenidate Product Candidate
KP415 End-of-Phase 1 Meeting with FDA Affirms KemPharm’s Development Plan and Potential NDA Submission as early as late 2018
Conference Call and Live Audio Webcast with Slide Presentation Scheduled for Today at 4:30 p.m. ET
CORALVILLE, Iowa, June 28, 2017 (GLOBE NEWSWIRE) -- KemPharm, Inc. (NASDAQ:KMPH), a clinical-stage specialty pharmaceutical company focused on the discovery and development of proprietary prodrugs, today announced two significant advances involving its prodrug development pipeline for the treatment of attention deficit hyperactivity disorder (ADHD). These advances include the development of a new prodrug product candidate of d-threo-methylphenidate (d-MPH), KP484, for ADHD indications that may benefit from a super-extended duration of treatment and the successful completion of an End-of-Phase 1 (EOP1) meeting with the U.S. Food and Drug Administration (FDA) for KP415.
KP484 – Prodrug of d-MPH for Super-Extended Duration Treatment of ADHD
KP484 is KemPharm’s newly developed prodrug product candidate for a super-extended release (SER) d-MPH being designed for the treatment of ADHD in patients that respond best when a long duration of therapy beyond both KP415 and all current methylphenidate treatments is required. The new therapeutic application was developed during a data analysis of the KP415 Phase 1 study, in which KemPharm observed that the prodrug molecule demonstrated an ability to produce a longer duration release of d-MPH relative to comparator products available on the market today. As a result, KemPharm is now planning to initiate development of KP484 and anticipates filing an Investigational New Drug (IND) application for KP484 as early as the third quarter of 2017. KemPharm expects to leverage data from certain clinical and nonclinical trials of KP415 to expedite the development of KP484. KemPharm believes that this may enable it to realize key cost and R&D efficiencies and target a New Drug Application (NDA) submission as soon as 2019.
KP415 – Prodrug of d-MPH for Treatment of ADHD with Early On-set and Better Total Duration
KP415 is KemPharm’s extended release (ER) d-MPH prodrug product candidate designed for the treatment of ADHD with patients that could benefit from both earlier onset as well as better total duration of effect. As previously indicated, KemPharm held an EOP1 meeting with the FDA to discuss the data from the Phase 1 proof-of-concept clinical trial of KP415 (KP415.101), additional nonclinical and manufacturing data sets, and the proposed clinical and nonclinical programs required for eventual submission of an NDA for KP415. Additionally, KemPharm and the FDA discussed the proposed commercial formulation of KP415, which KemPharm plans to develop with a layer of methylphenidate to potentially support a superior early onset profile. Based on the feedback from the FDA, KemPharm believes that its ongoing and anticipated research of KP415, including the pivotal efficacy trial, which KemPharm plans to initiate in the second half of 2017, remains on schedule and in alignment with an NDA submission as soon as late 2018. KemPharm also anticipates that it will initiate a human abuse liability (HAL) program of KP415 beginning in the second half of 2017 to assess the potential for the prodrug to deter intranasal, intravenous and oral abuse. KemPharm expects data from the HAL program and the ongoing pharmacokinetic (PK) studies will be available in the second half of 2017 and early 2018. KemPharm plans to utilize the data from both studies in the development KP484, as well.
“We now believe KemPharm’s ADHD prodrug portfolio is the company’s most valuable asset. In our view, the advances that we have made with KP415 and our newly developed product candidate for a super extended treatment, KP484, further support this belief,” stated Travis C. Mickle, Ph.D., President and Chief Executive Officer of KemPharm. “We continue to view KP415 as our highest value product candidate, and we are excited to now take this prodrug to the next phase of its development. Since our quarterly update in May, we have initiated several pharmacokinetic studies of KP415 with data from these studies expected during the second half of 2017 and in early 2018. Now, following the End-of-Phase 1 meeting with the FDA, we are prepared to develop the commercial formulation of KP415 and initiate the pivotal efficacy study and human abuse liability program for KP415 in the second half of 2017; all pointing towards an NDA submission for KP415 as soon as late 2018.”
“The success of our KP415 program is now heightened by the development of a new product we are designating as KP484, which we are planning to develop for patients that require a product that provides a much longer duration of treatment for their ADHD,” Dr. Mickle continued. “In contrast to Shire’s recently approved amphetamine-based MYDAYISTM for extended duration of treatment for ADHD, initial clinical data on KP484 suggest our new methylphenidate product could offer substantially longer duration when compared to other methylphenidate ADHD drugs which is clearly an unmet need in treatment with methylphenidate. Given this, we have now activated the development program for KP484 with our first milestone being an IND filing in the third quarter.”
“We believe physicians need products, such as KP415 and KP484, which are designed to provide solutions for their patients’ individual needs, recognizing that many may respond differently to different treatments. Thus, it is important for patients to have multiple treatment options,” Dr. Mickle concluded. “For example, some patients need milder therapies such as a methylphenidate-based option that may be just as effective and have fewer side effects when compared to amphetamine-based products.”
Conference Call Information:
The company will host a conference call and live audio webcast with slide presentation today, June 28, 2017, at 4:30 p.m. ET. Interested participants and investors may access the conference call by dialing either:
(866) 395-2480 (U.S.)
(678) 509-7538 (international)
Conference ID: 45888929
The live webcast with accompanying slides will be accessible via the Investor Relations section of the KemPharm website http://investors.kempharm.com/. An archive of the webcast and presentation will remain available following the call.
About KemPharm
KemPharm is a clinical-stage specialty pharmaceutical company focused on the discovery and development of proprietary prodrugs to treat serious medical conditions through its LATTM (Ligand Activated Therapy) platform technology. KemPharm utilizes its LATTM platform technology to generate improved prodrug versions of FDA-approved drugs in the high need areas of pain, ADHD and other central nervous system disorders. KemPharm’s co-lead clinical development candidates are KP415, an extended-release prodrug of methylphenidate for the treatment of ADHD, and KP201/IR, an acetaminophen-free formulation of the company’s immediate release abuse deterrent hydrocodone product candidate, KP201. For more information on KemPharm and its pipeline of prodrug product candidates visit www.kempharm.com.
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Idorsia - Actelion spin-off begins trading
https://www.reuters.com/article/us-idorsia-stock-idUSKBN1971SZ
DEALS | Fri Jun 16, 2017 | 9:26am EDT
Actelion spin-off Idorsia's shares rise 30 pct in market debut
Shares in Idorsia (IDIA.S), the drug pipeline firm spun off from biotech group Actelion (ATLN.S) after Johnson & Johnson's (JNJ.N) $30 billion takeover, rose nearly 30 percent after making their market debut at 10 Swiss francs each on Friday.
They advanced to nearly 13 francs in early afternoon business in Zurich, valuing the company at above 1.5 billion Swiss francs ($1.54 billion).
One trader said Idorsia's stock had been trading over the counter this week at around 8 francs, the theoretical price given the difference between Actelion's share price in Swiss francs and the $280 cash per share price J&J is paying for Actelion.
Allschwil-based Idorsia is starting out with around $1 billion in cash and nine investigational drugs in early or mid-phase trials against diseases including hypertension, insomnia and acute coronary syndrome.
Chief Executive Jean-Paul Clozel said he hoped to rapidly move Idorsia's molecules closer to regulatory approval, although that is still likely to be years away.
"We're going to develop a commercial structure as quickly as possible," Clozel told Swiss state television in an interview.
Actelion shareholders got one Idorsia share for each Actelion share they held on June 13.
J&J (JNJ.N), which will control up to 32 percent of Idorsia, intends to delist Actelion after buying it to gain access to its portfolio of drugs including Tracleer and Uptravi against pulmonary arterial hypertension, a deadly lung disease.
($1 = 0.9743 Swiss francs)
(Reporting by Michael Shields, Rupert Pretterklieber and John Miller; Editing by Joshua Franklin and Adrian Croft)
EPIX - EPI-506 P1 data
[Peter, do you still follow EPIX? I have always kept an eye on them as agree this seems to be a very novel approach and always seemed to be big potential reward if panned out given valuation. However, the delay in moving the drug into and through the clinic and their very poor financial condition has always kept me away. Not sure this new data does anything to change my mind. At this point, would seem like they need to either do a large share offering to give them some room to get through to actual P2 PoC data or otherwise accept whatever terms they can get from a partner. I don't know if the AEs could be an issue as they are still trying to ramp up the dose.]
http://www.essapharma.com/wp-content/uploads/2017/06/BRANDED_ESSInc_Press-Release_ASCO_Data_FINAL-COPY.pdf
ESSA PHARMA PRESENTS DATA FROM PHASE 1 TRIAL OF EPI-506 AT 2017 ASCO ANNUAL MEETING
- Well tolerated to date with an acceptable safety profile
- Signs of clinical activity at the higher dose range
- Enrollment continues in additional cohorts at higher dose levels
Houston and Vancouver, Canada, June 5, 2017 – ESSA Pharma Inc. (TSX: EPI; NASDAQ: EPIX) (“ESSA” or the “Company”), a clinical-stage pharmaceutical company focused on the development of novel small molecule drugs for the treatment of prostate cancer, announced that early data from the Phase 1 portion of the ongoing Phase 1/2 clinical trial of its product candidate, EPI-506, were featured in a poster presentation during the 2017 American Society for Clinical Oncology ("ASCO") Annual Meeting held in Chicago.
Prostate cancer specialist, Kim N. Chi, M.D., at the BC Cancer Agency in Vancouver, presented the poster entitled, “Efficacy, safety, tolerability and pharmacokinetics of EPI-506 (ralaniten acetate), a novel androgen receptor ("AR") N-terminal domain ("NTD") inhibitor, in men with metastatic castration-resistant prostate cancer ("mCRPC") progressing after enzalutamide and/or abiraterone.”
The data presented were from the Phase 1 portion of the ongoing Phase 1/2 clinical trial of EPI- 506. The open-label, single-arm, dose-escalation study is evaluating the safety, pharmacokinetics, maximum tolerated dose ("MTD"), and anti-tumor activity of EPI-506 in men with end-stage mCRPC who have progressed after prior enzalutamide and/or abiraterone treatment, and may have received one prior line of chemotherapy. Twenty-one patients were available for analysis as of the May 12, 2017 ASCO data cut-off and each patient had received four or more prior therapies for prostate cancer at the time of study entry.
The 21 patients self-administered oral doses of EPI-506 ranging from 80 mg to 2400 mg, with mean drug exposure of 87 days (range of 21 to 427 days). Seventeen patients discontinued treatment, primarily due to progressive disease, and four remain on study. Three patients have undergone prolonged treatment (median of 286 days; range 219 – not reached), after intrapatient dose escalation. Prostate-specific antigen (“PSA”) declines ranging from 4% to 29% have been observed in four patients at higher doses (≥1280 mg). An analysis of human drug exposures (AUC) compared to exposure levels derived from a xenograft model of castration resistant prostate cancer (“CRPC”) showed that EPI-506 doses of ≥2400 mg were beginning to reach the anticipated target range for significant tumor growth inhibition as indicated by the model. Additional Phase 1 cohorts continue to be enrolled to evaluate a 3600 mg dose (either once-daily or 1800 mg twice-daily).
EPI-506 was well tolerated and demonstrated an acceptable safety profile in doses up to 2400 mg. No treatment-related serious adverse events were reported. The most common adverse events ("AEs") were diarrhea (8/21) and nausea (6/21), either Grade 1 or 2. Anemia was the only AE ≥Grade 3 observed in more than one patient (3/21) but was considered by investigators to be unrelated to EPI-506. Other AEs ≥Grade 3 considered potentially related to EPI-506 included a single case of elevated AST reported as possibly related, and a single case of elevated amylase deemed probably related ("DLT").
“To see some indication of PSA responses in such a heavily treated patient population is encouraging. Given the acceptable safety and tolerability seen to date, we look forward to additional data that will be forthcoming from patients receiving higher doses of EPI-506,” said Dr. Chi. “Prostate cancer is the second most common cancer in men. Despite the therapeutic advances made in recent years, prostate cancer patients eventually progress on these treatments, so finding new options to complement or follow these therapies is absolutely essential.”
“EPI-506 represents a novel approach to blocking the androgen pathway, and we are very pleased to have our first clinical data presented at ASCO,” said David R. Parkinson, M.D., President and Chief Executive Officer of ESSA. “We have observed signs of clinical activity at the higher doses in this analysis, which correlates with our preclinical modeling, and are continuing to enroll patients in dose cohorts higher than those reported here.”
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