Wednesday, May 17, 2017

CRISPER-Cas9 - Intellia Therapeutics

We previously wrote about the science of CRISPER-Cas9.. Over the weekend Intellia Therapeutics released data at the American Society of Gene & Cell Therapy Annual Meeting with this press release Intellia PR. With this news the company may be getting closer to in human clinical trials for the first time. Intellia Therapeutics is our favorite Crisper-Cas9 company for many reasons, but primarily because of their collaborations with Novartis, Regeneron. Still many years away from any FDA approval for any indication, the company is worth monitoring, along with it's competitors Crispr, Editas, and Cellectis.    Thank you for reading.


Tuesday, May 2, 2017

CTP-543 Clinical Trial Initiated

This phase 2 for Alopecia Areata will have a primary endpoint with the number of responders achieving at least 50% improvement in SALT score at 24 weeks.

Estimated Enrollment: 100               
Anticipated Study Start Date:May 2017
Estimated Study Completion Date:July 2018
Estimated Primary Completion Date:March 2018 (Final data collection date for primary outcome measure)
ArmsAssigned Interventions
Experimental: CTP-543, 4 mg
Oral tablet, dosed twice-daily
Drug: CTP-543
Experimental: CTP-543, 8 mg
Oral tablet, dosed twice-daily
Drug: CTP-543
Experimental: CTP-543, 12 mg
Oral tablet, dosed twice-daily
Drug: CTP-543
Experimental: CTP-543, 16 mg
Oral tablet, dosed twice-daily
Drug: CTP-543
Experimental: Placebo
Oral tablet, dosed twice-daily
Drug: Placebo

Detailed Description:
This is a double-blind, randomized, placebo-controlled, parallel dose-comparison, multi-center study of CTP-543. Subjects will be randomized to either an active dose of CTP-543 or placebo for an initial 24-week efficacy period. A 28-week dose-adjustment period will follow where patients tolerating treatment may adjust dose at Week 24 as needed, and placebo patients will be switched to active treatment.
Below is a daily chart of Concert Pharmaceuticals. The stock has been basing since the big move higher on March 6, when the company announced the sale of CTP-656 to Vertex. Thank you for reading.

Saturday, April 15, 2017

CTP-543 Patent Challenge by Incyte Corporation

On April 7th, Concert Pharmaceuticals CTP-543 (deuterated Ruxolitinb) patent was challenged for Inter Partes Review (IPR). The filing details are listed below.

Trial Number - IPR2017-01256
Filing Date - 4/7/2017
Patent # - 9,249,149
Tech Center - 1600

We have written about the Inter Partes Review process, and felt that if one of Concert's deuterated drugs were going get a patent challenge it would go through this process. Inevitably this was going to happen sooner or later, and perhaps sooner is overall better for the company. Below is a list of Pro's and Con's that I came up with.
  • The patent office issued a deuterated Ruxolitinib patent to Concert Pharmaceuticals.
  • Concert's patent for deuterated ruxolitinib has Alopecia Areata listed as a potential indication that CTP-543 will be tested for. 
  • Incyte Corporation's patent for Ruxolitinib, does not list Alopecia Areata as a target indication.
  • Original Ruxolitinib patent has zero mention of deuteration in the patent. 
  • The drug, per company press release exhibits a 20% reduction in dosing. A 16mg tablet of CTP-543 has similar dosing characteristics as a 20mg dosage of Ruxolitinib.   
  • Outside of a 20% dosing advantage that CTP-543 has shown, the two drugs are dosed twice daily, as the half-life, and the metabolite profiles, are similar from Concert press releases. Challenge based on obvious.
  •  The only other deuterated drug patent challenge, Auspex Pharma's Venlafaxline, stated in their litigation that the "deuterated venlafaxine claimed in the '317 patent however, has superior pharmacokinetic properties compared to venlafaxine, including increased half-life, reduced Cmax, and reduced inter-patient variability."
Bottom Line
We don't know which factor is seen as the most important in drug patent litigation. If it is specific for the drug indication intended use, then Concert should have a very strong case as Alopecia Areata is listed in their deuterated Ruxolitinib patent, and Incyte Corporation's patent does not list Alopecia Areata within their patent as an intended indication. On the other hand, if drug pharmacokinetic, metabolites, and dosing frequency differentiation is an important factor in determining the outcome, then Incyte may get the nod, as Concert has even stated the two drugs are similar, except for the 20% dosing reduction that CTP-543 has shown in phase 1 clinical trials. Thank you for reading.


Wednesday, March 29, 2017

AVP-786 for Neurobehaviorial Disinhibition

A new clinical trial AVP-786 was recently posted on the website. Avanir Pharmaceuticals (the company Concert Pharmaceuticals licensed AVP-786 to) will be initiating AVP-786 for patients who experienced a traumatic brain injury (TBI), and suffer from neurobehavioral disinhibition, including aggression, agitation, and irritability. The phase 2 clinical trial is planning on enrolling 150 patients at 17 U.S. locations. The completion date is estimated to finish in December of 2019. More importantly, this is further validation that Otsuka is committed to furthering AVP-786 for neurological indications. Concert could achieve royalties in the mid single digits to low double digits based on AVP-786 future sales. Thank you for reading.


Thursday, March 9, 2017

CTP-656 Sold to Vertex Pharmaceuticals for $250 Million

Very nice news from Concert Pharmaceuticals on Monday March 6th.  CTP-656 for cystic fibrosis nets $160 million upfront, and another $90 million in milestones for the sale to Vertex Pharmaceuticals, closing by October 31st.  This deal gives Concert around $250 million (in present terms) cash on hand, with a cash runway into 2021.   The focus will be CTP-543 for Alopecia Areata, and to broaden their future pipeline.  With the upfront $160 million, the company will have around $11.50 per share in cash, zero debt.  Below is a 60 minute chart of CNCE.  The stock has gained 76% this week through Thursday. 

Bottom Line:
A well timed move by management to get the cash without diluting shares at extremely undervalued prices.  The future now is with CTP-543 for the initial indication of unmet need Alopecia Areata, and potentially others to follow. Thank you for reading. 

Saturday, February 25, 2017

GLPG2451 for Cystic Fibrosis

Galapagos is aggressively pursuing drugs for people living with cystic fibrosis.  We previously wrote about Galapagos extensively here Galapagos.  Their previous top candidate, potentiator GLPG1837, has now been put on hold for a much more convenient once daily dosed potentiator GLPG2451.  The drug has completed the safety phase 1 clinical trial in healthy subjects, and by Galapagos standards was viewed as ready for a phase 1 combo trial with their lead corrector GLPG2222.  The ultimate goal for the company is to develop a triple combination for people with the F508del mutation, which represents around 90% of the total CF population.  The phase 1 and 2 clinical trials are being funded almost 100% by their partner AbbVie.  If this phase 1 combo clinical trial passes the safety test, then a third component corrector GLPG2737, which is currently in the safety phase of testing, will then be added to the combo 2451 and 2222 to form the triple.  The big picture goal is to produce a better therapy than currently approved Vertex's two drug combo Orkambi.  A once daily triple combo would be advantageous for CF patients that may take up to 20-40 pills per day for this disease. 

Interim Analysis of 2451 and 2222
According to Galapagos, an interim analysis will be conducted on the combo mid-year.  If the combo passes the safety test, then corrector #2 GLPG2737 will then be added to the mix, and the three drugs will be tested for CF patients with F508del around third quarter of 2017.  So, by the end of 2017, the first triple combination (one potentiator, and two correctors) will be tested.  However, if the current phase 1 clinical trial with 2451 and 2222, does not produce an acceptable drug/drug interaction safety profile in healthy participants, then the entire project would be delayed.   

CTP-656  in Phase 2
Concert Pharmaceuticals CTP-656 is currently in a phase 2 clinical trial as mono-therapy for CF patients harboring the G551D mutation.  The drug is dosed once daily, and has shown head to head comparison's with Kalydeco in several early clinical trials with PK advantage.  The drug could fit nicely into the mix for a combo also, with two correctors, dosed as one simplified daily pill for F508del CF patients. 

Bottom Line
We'll monitor progress of the Galapagos combo clinical trial (2451 + 2222), and CTP656's phase 2 clinical trial that is scheduled to complete by the end of 2017.  Thank you for reading. 


Sunday, February 19, 2017

Concert Pharmaceuticals Upcoming Event Sheet

Busy time for events and clinical trial updates for the company in the next couple of months.
  • Fourth quarter conference call, within next two weeks
  • Progress of CTP-656 with FDA
  • Start date for CTP-543
  • Cowen conference March 6-8
  • Roth conference March 12-15
  • Barclays conference March 14-16
  • TEVA Pharmaceuticals FDA approval date (first deuterated drug)
  • AVP-786 Residual Schizophrenia phase 2 clinical trial nearing complete April
The most important from above, is the progress of CTP-656 with the FDA, and the start of phase 2 clinical trial with CTP-543 for Alopecia Areata, which was previously guided for the first quarter of 2017.  Thank you for reading.    


Saturday, January 21, 2017

CTP-656 Receives Orphan Drug Designation

Concert Pharmaceuticals received Orphan Drug Designation from the FDA in press release here, Orphan Drug Designation for CTP-656 for the Treatment of Cystic Fibrosis.  The significance of this, is that CTP-656 could receive up to seven years of marketing exclusivity, and even more importantly, gets FDA assistance in clinical trial design.  Orphan Drug Designation is given to a disease or condition that affects less than 200,000 people in the U.S.  Thank you for reading.


Saturday, January 14, 2017


CTP-543 is the deuterated version of FDA approved drug Ruxolitinib, which is approved for myelofibrosis, and polycythemia vera.  Concert Pharmaceuticals plans to address unmet need Alopecia Areata with CTP-543.  Proof of concept was confirmed with this academic clinical trial, by Columbia University here JCI.  The company will be in a phase 2 clinical trial with around 100 participants beginning in the first quarter of 2017, with readout by the end of year.  Thank you for reading.


Friday, January 6, 2017

Super Refractory Status Epilepticus (SRSE)

Sage Therapeutics - SAGE, is currently in phase 3 for unmet need (SRSE) with drug SAGE-547.   SRSE is a rare neurological condition, and a sub-type of Status Epilepticus (SE), which is a prolonged seizure.  A diagram from this link explains the stages. The Treatment of Super-refractory Status Epilepticus.

Click to Enlarge 
SAGE Therapeutics has a Special Protocol Assessment (SPA) with the FDA for this phase 3 clinical trial.  The company mentioned, that Refractory Status Epilepticus (RSE) has up to 50% response rate, and that (SRSE) has approximately 35% response rate.  The trial should complete first half of 2017.  Thank you for reading.


Sunday, January 1, 2017

CTP-656 For Cystic Fibrosis

CTP-656 is the name of Concert Pharmaceuticals deuterated version of Vertex's Kalydeco, which is approved for cystic fibrosis patients with the G551D mutation, and as combo with corrector Lumacaftor (known as Orkambi), for patients with the F508del mutation.  The hope is that CTP-656 enhances therapy for cystic fibrosis patients by improving the metabolic profile, reduce dosage to once daily, or ameliorate drug interaction, over currently FDA approved Kalydeco.  Thank you for reading.


Friday, December 30, 2016

SAGE-217 Clinical Trial Progress

Sage Therapeutics' SAGE-217 is the companies next generation oral CNS drug for a variety of indications.  The company has completed the required phase 1 studies, and is now running phase 2, proof of concept clinical trials listed below with expected readout of data.  The four clinical trials can be found at here SAGE-217.

Severe Postpartum Depression - June 2017
Essential Tremor - December 2017
Moderate to Severe Major Depressive Disorder - December 2017
Parkinson's Disease of Moderate Severity - June 2017

Sage Therapeutics has many clinical trials currently running.  The company has $431 million in cash, and patent to 2033.  Thank you for reading. 


Friday, December 23, 2016

GLPG1837 for Cystic Fibrosis

Galapagos released phase 2, SAPHIRA(1) results this week with drug GLPG1837, for Cystic Fibrosis patients with the G551D mutation.  The link to the conference call is here

Some details from the conference call:
  • The company reported similar ppFEV1, in comparison to FDA approved Kalydeco
  • Kalydeco patients at baseline had a sweat chloride reading of around 45 mmol/L
  • After the seven day washout period, the sweat chloride level increased to a mean value of 98 mmol/L*
  • After 28 days, and dosing up to 500 mg GLPG1837 twice daily, sweat chloride fell to 66 mmol/L
  • For patients who exceeded the predicted target concentration, sweat chloride changed from a mean 94 mmol/L to 52 mmol/L
  • Sweat chloride did not fall to the original baseline Kalydeco level, of around 45 mmol/L
  • GLPG1837 was mentioned as being dose limited up to 600 mg twice daily
* The concentration of chloride in sweat is elevated in individuals with CF.

Thank you for reading.