Sunday, July 30, 2017

CTP-656 Cleared for Sale to Vertex Pharmaceuticals

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. They 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 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, 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
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 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.
  • 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.