Minerva Neurosciences Raises Capital - $8.45

Minerva Neurosciences (NERV) filed Form S-3 on August 10. The form S-3 is a three-year prospectus that allows the company to from time to time, at their discretion, sell shares to raise capital up to $200 million. The supplemental part of the prospectus calls for a takedown of up to $50 million worth of stock sales through investment banker Jeffries. The company held approximately $108 million in cash as of 6-30-18. If the company initiates the complete takedown of $50 million, then the cash will increase to around $156 million, and the dilution would be around 6.2 million shares at current prices to increase the total share count to 45 million shares outstanding.  The companies burn rate is around $13 million per quarter at present.
The phase 3 clinical trial readout of MIN-101 for negative symptoms of schizophrenia, is scheduled for the first half of 2019. So beginning the capital raising process now makes sense. The S-3 filing gives the company the discretion of when and how much capital to raise over the next three years. Below is a chart of Minerva. Thank you for reading.

SAGE-718

Sage Therapeutics' focus is on developing compounds that are positive allosteric modulators (PAM) of both synaptic and extrasynaptic sites of either the GABA receptor or the NMDA receptor system.
The companies second area of focus is on the NMDA receptor with SAGE-718. SAGE-217 targets the GABA receptor, SAGE-718 targets the NMDA receptor. The company is currently in phase 1 testing with oral drug SAGE-718.
The unique position the company finds itself in, is unlike SAGE-217 which primarily targets depression, SAGE-718 will target different indications with zero overlap. Within NMDA hypofunction the company is targeting indications such as Huntington’s, ADHD, and Alzheimer’s disease, potentially creating another very large revenue stream in the future. The company has SAGE-904 which also target’s the NMDA receptor and is in pre-clinical studies.

The patent for SAGE-718 from the company’s 10K below.

We also own twenty families of applications directed to modulators of NMDA receptors. Fifteen of these families of patent applications are directed to compounds that modulate NMDA receptors, including SAGE-718, which can be used to treat NMDA receptor-related disorders such as CNS-related conditions. One of these families of patent applications is directed to using a naturally occurring compound as a biomarker for a subject who would benefit from treatment with a modulator of NMDA receptors. One of these families of patent applications is directed to using a modulator of NMDA receptors to treat a rare NMDA loss of function disorder. Any patents that may issue, if any, from these families of applications directed to modulators of NMDA receptors would have statutory expiration dates in September 2032 and October 2037.

SAGE-217 Gets Expedited Development - $175.76

Very good news from SAGE Therapeutics this morning. The FDA has agreed to give SAGE Therapeutics an expedited pathway for oral drug SAGE-217 for the indications of Postpartum Depression (PPD) and Major Depressive Disorder (MDD). Below is copied directly from the press release this morning.

• Expedited SAGE-217 development plan to support potential NDA submission for MDD and PPD together
•  Previously completed placebo-controlled study in MDD considered as pivotal; initiation of one additional Phase 3 pivotal trial anticipated in 2H of 2018  
• Ongoing study in PPD designated as pivotal; results expected in 4Q 2018
• If successfully developed, SAGE-217 has the potential to be the first durable, rapid-acting, oral, short-course treatment for MDD and PPD

The second half of 2018 will be packed with clinical trial data for PPD and MDD. SAGE-217 is an oral once daily delivered drug with patent to April 2034. Thank you for reading.

Neuroactive Steroids (NAS)

Not all neuroactive steroids are created equal from this chart and abstract below. That may be important when comparing Sage Therapeutics SAGE-217 to Marinus Pharmaceuticals drug Ganaxolone for patients with Postpartum Depression. First let's look at a chart that compares oral SAGE-217 to IV SAGE-547 and IV Ganaxolone for synaptic and extrasynaptic activity of each.

 

SAGE-217 shows much more activity in both synaptic and extrasynaptic activity over a given time period.  Below is another illustration that not all is created equal when considering tonic current. https://www.ncbi.nlm.nih.gov/pubmed/27743930. Here is a paragraph from that abstract.

A sustained increase in tonic current was observed following exposure to ALLO, or SGE-516 and was prevented by inhibiting PKC with GF 109203X. No increase in tonic current was observed with exposure to ganaxolone. In agreement with the observations of an increased tonic current, the NASs ALLO and SGE-516 increased the phosphorylation and surface expression of the β3 subunit-containing GABAARs. Our studies demonstrate that neuroactive steroids have differential abilities to induce sustained increases in the efficacy of tonic inhibition by promoting GABAAR phosphorylation and membrane trafficking dependent on PKC activity.

Thank you for reading.

Brexanolone for Postpartum Depression Submital to the FDA - $145.29

Today, SAGE Therapeutics announced the submittal of a New Drug Application to the FDA for approval of Brexanolone for Postpartum Depression. There is not an FDA approved drug to treat this indication, so this could potentially be the first. I am expecting six months to approval or around October 23, 2018. The company achieved their goal of submittal to the FDA during the first half of 2018 comfortably. The patent for Brexanolone runs to 2034. Thank you for reading.

Esketamine for Depression

This post will focus on Johnson & Johnson's NMDA intranasal Esketamine (form of Ketamine) for treatment resistant depression or (TRD), with rapid onset of effect. Esketamine has received breakthrough therapy designation (BTD) from the FDA in 2013 for treatment-resistant depression, and again in 2016 for major depressive disorder with imminent risk of suicide.  JNJ through Janssen has several Esketamine phase 3 clinical trials for TRD patients currently running. Results from a phase 2 clinical study for patients 20-64 years of age with treatment resistant depression, (lack of treatment with at least two different oral anti-depressants) released results.  The results by Janssen showed a statistically significant effect, with ascending dose-response relationship, and response was observed as quickly as two hours post dose.  The side effect profile is better explained here JAMA Psychiatry in etable 4 supplemental 1. A rundown of the side effect profile from that supplemental is below. 
                                                                56mg                     84mg
Dizziness                                                40%                         47%
Headache                                               15%                          18%
Dissociation                                           35%                         24%
Dysgeusia                                               15%                          29%
Nausea                                                    20%                         24%
Dissociative  Disorder                           5%                          24%               
Oral Hypoesthesia                               20%                          12%     

We'll have to see how the FDA addresses the side effect profile of the intranasal drug. Thank you for reading.
 

SAGE Therapeutics Market Capitalization in Charts - $183.47

Sage Therapeutics - (SAGE) has a CNS drug with a unique fast acting mechanism of action, that has led the company to a current $7.41 billion dollar market capitalization. Previous writing's  about the company can be found here SAGE. Below is a market capitalization chart of SAGE, at certain stock prices.

The current market capitalization of the company is around $7.41 billion. We see SAGE reaching a $10 billion market cap ($240.00) in the near future based solely on their current pipeline, potentially reaching a $15 billion market cap ($361.00) on further success for SAGE-217 in other indications, and potential buyout of the company. The patent for SAGE-217 and SAGE-547 run to 2034. Thank you for reading.

Contact: 586-431-8000

MIN-101 Phase 3 Primary Endpoint - $6.80

Minerva Neurosciences (NERV) has officially begun dosing patients for their pivotal phase 3 clinical trial for the negative symptoms or Schizophrenia. Let's examine the primary endpoint in the phase 3 (Marder NSFS) and compare it with their successfully completed phase 2 primary endpoint PANSS Negative Scale (Pentagonal Structure 5-Factor) to see how the items vary. Below is the phase 2.

Phase 2   PANSS Negative Scale (Pentagonal Structure)            p = 32mg  64mg
N1            Blunted Affect                                                                               .25         .17
N2            Emotional Withdrawal                                                               .01         .02           
N3            Poor Rapport                                                                               .00         .00
N4            Passive/apathetic social withdraw                                          .29         .01
N6            Lack of spontaneity and flow of conversation                      .07          .01
G7            Motor retardation                                                                       .68         .04
G8            Uncooperativeness                                                                     .41          .86
G13          Disturbance of volition                                                              .25          .88
G14          Poor impulse control                                                                  .89         .56

Phase 2   5-Factor Negative Score
32mg p=0.021   effect size 0.45     64mg p=0.003  effect size 0.58

Below is the phase 3 Marder NSFS (negative symptom factor score) items that will be tested versus placebo.

Phase 2   Marder Negative Symptoms Factor Score (NSFS)       p = 32mg  64mg
N1             Blunted Affect                                                                             .25         .17
N2            Emotional Withdrawal                                                              .01         .02
N3            Poor Rapport                                                                               .00         00
N4            Passive/apathetic social withdraw                                          .29         .01
N6            Lack of spontaneity                                                                    .07         .01
G7            Motor retardation                                                                       .68         .04
G16          Active social avoidance                                                              .01         .00

Notice that the phase 2 design included G8, G13, and G14, which scored the lowest on effect for the phase 2 primary endpoint, but will not be included in the phase 3 Marder (NSFS) primary endpoint. The currently running phase 3 primary endpoint includes the same items as the phase 2, (minus G8, G13, G14) with the inclusion of G16 (active social avoidance) which scored a .01 and .00 respectively in the phase 2 clinical trial. The Marder items that were included in the phase 2, would have scored better in itself, than the phase 2 primary endpoint PANSS Negative Scale (Pentagonal Structure) 5-Factor Negative Score of p=0.021 and p=0.003, which was achieved with the 32mg and 64mg dose. Thank you for reading.
   

Patent Board Does Not Institute PGR Proceeding

The press release is here Concert Pharmaceuticals Announces Patent Trial and Appeal Board Did Not Institute PGR Proceeding.  What this means to Concert Pharma is that, Incyte Corporation may be able at some point in time, challenge the patent of CTP-543. The second setback was that Concert has announced that they will not at this time initiate further clinical trials for other auto-immune indications that CTP-543 may have been useful for. The company continues to proceed with CTP-543 in their phase 2 clinical trial for patients with Alopecia Areata.  In addition the phase 3 clinical trial for AVP-786, which was scheduled to read out in July of 2018, has been pushed back to April of 2019, eliminating a potential catalyst for the company in 2018. The second half of 2019, which should reveal AVP-786's trial success, and phase 2 CTP-543 12mg arm effectiveness for Alopecia Areata patients, should be an important time for the company. Thank you for reading.

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.
 

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.

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.