Sunday, December 17, 2017

Minerva Neurosciences - $6.05

We wrote about Minerva Neursciences  (NERV) when they were just completing some important corporate goals in anticipation of upcoming clinical trials. The lead drug is MIN-101 for negative symptoms of Schizophrenia, which is scheduled to start a 500 patient study soon. Patients will be recruited throughout Europe, with 30% of participants coming from the US. Currently there is not an FDA approved drug for negative symptoms of Schizophrenia, so this fits into our category of an unmet medical need. The phase 2 clinical trial with MIN-101 proved to be effective. The results of that clinical trial are below.
 
PANSS Negative Symptom Score at 12 Weeks
  • 32mg  p = 0.021    effect size   .45
  • 64mg  p = 0.003   effect size .  58
The 500 patient phase 3 study is to determine if MIN-101 is effective again, for the negative symptoms of Schizophrenia. The patent for MIN-101 extends out to 2035. Thank you for reading.
 

Saturday, November 25, 2017

Concert Pharmaceuticals - $22.93

Using technical analysis as a tool to track where your stock has been trading, and potentially heading is interesting. A weekly chart of Concert Pharmaceuticals, CNCE is below.
The all-time high for the stock is right at the $25.00 dollar mark, which occurred in 2015. The company has since evolved with a patent victory, and the broadening of the pipeline, which will be announced in early 2018. INCY is a stock we currently do not hold, but are tracking. The company is the owner of the drug Ruxolitinib, commercially known as Jakafi, a Janus Kinase Inhibitor (JAK). A weekly chart is below.
INCY is down around 33% from it's recent high of around $149.00, creating a lower risk entry point in the near future. The relative strength index (RSI) is near the two year low, as confirmation. Lastly, the S&P 500 has been on a tare higher throughout 2017 without any kind of meaningful pullback at all. The S&P 500 is higher around 18% on the year. Notice the RSI on the weekly chart below, is in very overbought territory, the highest reading that it's seen during the last three years.

Bottom Line: Charting stocks and indices can be interesting, and help to create better, lower risk entry points for the stocks that we are interested in. CNCE is approaching the all-time high and a breakthrough of the prior resistance of $25.00 would lead to fresh highs. INCY has been sold off creating a lower risk entry point sometime in the future. The S&P 500 on the weekly chart is as overbought more than anytime during the last three years.  Thank you for reading.

Saturday, November 11, 2017

Concert Pharmaceuticals 3rd Quarter Results - $17.53

The company announced third quarter results on Thursday 11-9-17. The company benefited from the sale of CTP-656 to Vertex as a one-time revenue that produced results of $5.61 in earnings per share for the quarter. More notable were some other developments.
  • Cash runway of $207 million expected to last into 2021
  • Expanded pipeline with a new neurological indication forthcoming
  • A second indication for CTP-543 will be announced in 1st quarter of 2018
  • Phase 2A for Alopecia Areata 4mg dose completed enrollment
  • Data Monitoring Committee to give safety opinion around February 2018 4mg dose
  • PGR  (Post Grant Review) of Incyte's deuterated Ruxolitinib to be decided in January 2018
Bottom Line:
The next important catalyst to watch for is the PGR decision to be made in January of 2018, the DMC decision for 4mg of CTP-543 around February, and two new indications will be announced early 2018. Thank you for reading.
 

Friday, October 20, 2017

CTP-543 Clears Patent Challenge - $16.09

The press release is here PTAB Denies Incyte Petition Challenging CTP-543 Patent. More importantly drug deuteration is as strong as ever with the following five victories under it's belt.

1. Auspex deuterated form of venlafaxine challenge was denied.
2. Auspex purchased by TEVA Pharmaceuticals for  3.5 billion.
3. Austedo first deuterated drug approved by FDA for  Huntington's chorea.
4. Vertex purchasing CTP-656 for up to 250 million.
5. CTP-543 patent holds validity versus Incyte Corporation.

This completes the CNCE Three Hurdles To Clear, and now the company can solely focus on developing CTP-543 for Alopecia Areata, and a second soon to be announced indication. Thank you for reading.

Sunday, October 1, 2017

Vertex Cystic Fibrosis Program

Vertex Pharmaceuticals (VRTX) has been, and will continue to be the leader in therapy for people with Cystic Fibrosis. Below is an update of all the different drugs in clinical trials that the company is currently running, including deuterated ivacaftor (VX-561), formerly known as CTP-656 that was purchased for $160 million from Concert Pharmaceuticals in July. Concert is eligible for up to $90 million more, dependent upon how far VX-561 progresses.

Twice Daily  
Ivacaftor 
Ivacaftor + Lumacaftor
Ivacaftor + Tezacaftor

Twice Daily Triple Combo Phase 2
Ivacaftor + Tezacaftor + VX-440 
Ivacaftor + Tezacaftor + VX-152
Ivacaftor + Tezacaftor + VX-659
Ivacaftor + Tezacaftor + VX-445

Once Daily Triple Combo Phase 2
VX-561 + Tezacaftor + VX-659 readout March 2018
VX-561 + Tezacaftor + VX-445 readout April 2018

The Ivacaftor patent runs to 2027, the Deuterated Ivacaftor (VX-561) patent runs into 2031. The goal for the program is to create a triple combo (1 potentiator, 2 correctors) once daily dosing for the majority of CF people with the F508del mutation. The company plans to run phase 3 triple combo trials in 2018.  Thank you for reading.

Sunday, July 30, 2017

CTP-656 Cleared for Sale to Vertex Pharmaceuticals - $15.11

The FTC (Federal Trade Commission) has terminated the waiting period for the sale of CTP-656 to Vertex Pharmaceuticals. CTP-656 is the deuterated version of Kalydeco which is approved for people with Cystic Fibrosis. This is another hurdle cleared which we wrote about CNCE: Three Hurdles to Clear. The company will now hold $260 million in cash or around $11.55 per share in cash. The third and last hurdle to clear will be the patent challenge for drug CTP-543 by Incyte Corporation. This one will take longer to circumvent. Thank you for reading.

Sunday, July 23, 2017

CTP-543 Patent Challenge Response

We wrote about the challenge to the patent here CTP-543 Patent Challenge by Incyte. In the lengthy preliminary response from Concert Pharma, and on page 67 was this. "Ruxolitinib has 18 hydrogens, which can create 218 – 1 = 262,143 different deuterated ruxolitinib analogs". That statement may hold importance on the challenge of obviousness.  Thank you for reading.                                            

Monday, July 10, 2017

Phase 2 CTP-543 Clinical Hold Lifted

Today Concert Pharmaceuticals announced that the phase 2 clinical trial of CTP-543 for Alopecia Areata will resume by the end of this month after a two month suspension. We initially wrote about this being one of three hurdles to be cleared CNCE: Three Hurdles to Clear.  The small downside is that the company will start the 24 week trial with the doses of only 4mg and 8mg, but with the potential to amend the protocol to explore higher doses. Prior to the suspension of the trial by the FDA, they were planning on using 4,8,12, and 16mg twice daily from the start. The FDA wants to take a measured approach for the development of using JAK inhibitors for various indications is what the company indicated. That coupled with the phase 1 clinical trials of CTP-543 that only lasted for 7 days of testing, makes sense.
The next hurdle to clear will be the pending sale of CTP-656 to Vertex, which is being considered by the FTC, whether it would be anti-competitive. I expect that second hurdle to clear in the next couple of months. Thank you for reading.
 

Thursday, June 29, 2017

Minerva Neurosciences (NERV)

Minerva Neurosciences, is a drug development company addressing the unmet need of Schizophrenia, with a focus on the negative symptoms of the disease. The company will be entering a pivotal phase 3 clinical trial in the second half of 2017 with 500 patients from the US and Europe. A bit of history into their phase 2b clinical trial produced significant results from this press release Phase IIb study of MIN-101. The company solved three underlying issues that prevented them from being investment suitable. 

1. Raising capital with a 5M share offering at $7.75, announced yesterday, bringing total cash to around 118M.
2. Ran a Bridging Study with a BFB-520 metabolite improved MIN-101, and have filed for patent that could exceed 2035 expiration for the GR version.
3. FDA approved their design of the phase 3 pivotal clinical trial that should initiate the second half of 2017.

Quick Facts
Shares: around 41 million
Cash: around 118 million
MIN-101 MR patent:  2035
MIN-101 GR patent:  2035+

There is not an FDA approved drug specifically for negative symptoms of Schizophrenia. Minerva is now in the lead as far as clinical trials initiated with the start of this phase 3 scheduled for the second half of 2017. Thank you for reading.
                                            

Monday, June 12, 2017

Concert Pharmaceuticals Raises $30 Million in Venture Debt Financing

Announced today, Concert Pharmaceuticals has raised $30 million in a debt financing agreement with Hercules Capital. This deal looks good in that it is not dilutive, and carries a prime-based variable interest rate of 8.55%. There were minimal warrants tied into the deal in the amount of 61,273 at an exercise price of $12.24. With this capital raise, the company should have at the end of the second quarter (June 30th), around $100 million in cash. This sum excludes the potential for another $160 million when CTP-656 is officially sold to Vertex. The loan matures June 2021, about the time when AVP-786 could potentially be on the market, FDA approved for agitation of the Alzheimer's type. Thank you for reading.

Sunday, June 4, 2017

CNCE: Three Hurdles to Clear

Prior to Concert Pharmaceuticals advancing as a drug development company addressing unmet medical needs, a few hurdles first need to be cleared.

Sale of CTP-656 to Vertex
1. Sale of CTP-656 to Vertex for 160 million upfront and potentially 90 million in future milestones. Closing the transaction will happen after it's determined that the Hart-Scott-Rodino Anti Trust Improvements Act (FTC) clears the way. If the transaction gets blocked due to anti-competitive monopoly concerns, then the company will have to consider a capital raise sometime in 2017, for the advancement of CTP-543 in clinical trials. Should the sale go through, the company will have around $10.00 per share in cash on hand, and runway into 2021.

Suspension of Phase 2 for Alopecia Areata
2. The FDA has put a temporary suspension on CTP-543's phase 2 clinical trial for moderate to severe Alopecia Areata. The company will be forwarding non-clinical toxicology studies, required by the FDA before proceeding. Once the company forward's the studies, the FDA will then have thirty days to respond. The company is expecting to resume the clinical trial around August 1st. The FDA has exhibited zero safety concerns with CTP-543 at this time. This is a low hurdle event, that will just take time to clear prior to resumption of the phase 2 trial.

Ruxolitinib Patent Infringement Claim By Incyte Corporation
3. We first wrote here CTP-543 Patent Challenge By Incyte. Concert has stated on prior conference calls, that they have sought out a third party patent specialist, and believe that they have freedom to operate drug CTP-543 for Alopecia Areata. There will be a response period addressing Incyte's claim of obviousness in the next few months. The height of this hurdle is still undetermined at this time, but more clarity should occur in the next few months.

Bottom Line:
Drug development is never easy, and not for CNCE as noted above. I think #1, should be cleared late summer, and #2 should be cleared around August 1st. #3, is a longer process to determine the outcome. Thank you for reading.

Wednesday, May 17, 2017

CRISPER-Cas9 - Intellia Therapeutics

We previously wrote about the science of CRISPER-Cas9. Over the weekend Intellia Therapeutics (NTLA) released data at the American Society of Gene & Cell Therapy Annual Meeting with this press release Intelliatx.com. 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, and 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
tablets
Experimental: CTP-543, 8 mg
Oral tablet, dosed twice-daily
Drug: CTP-543
tablets
Experimental: CTP-543, 12 mg
Oral tablet, dosed twice-daily
Drug: CTP-543
tablets
Experimental: CTP-543, 16 mg
Oral tablet, dosed twice-daily
Drug: CTP-543
tablets
Experimental: Placebo
Oral tablet, dosed twice-daily
Drug: Placebo
tablets

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
Title - DEUTERATED DERIVATIVES OF RUXOLITINIB
Patent Owner - CONCERT PHARMACEUTICALS INC.
Petitioner - INCYTE CORPORATION
Tech Center - 1600

We have written about what is considered obvious and referred to this well written article Deuterated Drugs: Unexpectedly Non Obvious?  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.
Pro's
  • 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.   
Con's
  • 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 clinicaltrials.gov 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 12, 2017

CRISPER-Cas9

We first wrote about the science here Crisper-Cas9This week, the messy patent issues have started to get resolved.  So, who are the winners and the losers, in this first round of patent battles.  The answer to those questions depends on what part of the country the original patents were filed from.  This link also has a background Broad Institute.

UC Berkeley
Caribou, CRSP, NTLA

MIT & Broad Institute: 
EDIT
Plants, livestock, humans. Will not have to re-negotiate intellectual property licenses.    

Both parties patents are valid, but the area that Crisper-Cas9 can be used varies depending on where the patents originated.  There is also the issue of US patents, and those outside the US.  We still have some outside US legal issues to be confirmed.  But as it stands today, EDITAS (EDIT), looks like the company least effected by the early legal decisions. 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

What is CTP-543

CTP-543 is the deuterated version of FDA approved drug Ruxolitinib, 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 90 participants beginning in the first quarter of 2017, with readout by the end of 2018. Thank you for reading.

Saturday, January 7, 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.