Some Observations on Northwest Biotherapeutics (NWBO), Neuralstem (CUR), Cytokinetics (CYTK) and Immuno-Cellular (IMUC) from Their Presentations at BIO CEO.
The BIO CEO Conference is being held in New York at the Waldorf Astoria on February 9 and 10 with a broad agenda of companies. You can go the websites of each company to hear their presentations. This note gives some highlights from the first day.
Northwest Biotherapeutics;
- A paper discussing results from the phase 1 trial of DCVax Direct involving 40 patients will be presented at a conference in Europe in March. This will be the first comprehensive look at the data; so far we have seen information on only a few patients. There will be an ongoing analysis of the data over the next year or two to follow the survival of patients so this will not be the first and only analysis, but it could provide good insight into the drug. You may recall that the lofty market capitalizations for Juno and Kite were based on phase 1 results for their CAR-T products so this could be an important inflection point for Northwest.
- There will be at least two phase 2 DCVax Direct trials running concurrently in 2015. The first will start in late 1Q, 2015 or early 2Q, 2015. My guess is that the trials will be in sarcoma and colorectal or pancreatic cancer. With adequate funding, they might do three. You may recall that Juno and Kite have not begun phase 2 trials although they will begin in 2015. These companies have suggested that phase 2 trials could be sufficient for regulatory approval if phase 1 results can be replicated
- The first interim look at the DCVax-L trial for efficacy will almost certainly occur in 2015. Because this look is triggered by a certain number of progression free survival events or deaths, it is not possible to pin point the time. This is the first look for efficacy and there are three possible recommendations from the Data Monitoring Committee: (1) stop the trial because it has successfully reached the primary end point of progression free survival, (2) the trial is unlikely to reach the end point and it is futile to continue or (3) continue the trial. The most likely outcome is point number 3.
- The negotiations that are necessary for reimbursement in Germany will be finished in 1H, 2015 and sales for glioma patients should begin. This process has taken longer than expected. NWBO is dealing with about 10 hospital groups and a like number of sickness funds (German insurance companies) to get IB apporvals to conduct the trials at hospitals and to contract reimbursement prices. This process has taken longer than the Company expected as dealing with all of these bureaucracies has been a headache. The company wanted to wrap up negotiations will all of the hospitals at about the same time to avoid one insurer playing off pricing against another.
- There were questions from the audience about a possible collaboration between Northwest and one of the companies developing checkpoint modulators. You may recall that Advaxis announced collaborations for its cancer vaccine and products from Merck and Astra. This along with some other events was instrumental in moving the stock from about $4 to about $11. There was no guidance on when or if that would occur although the Company has hinted that there is a possibility in coming months.
Neuralstem
- Results from the phase 2 trial of NSI-566 neural stem cells in ALS will be announced in late February or early March. This trial involved 15 patients and 18 surgeries. The Company mentioned that the lead investigator, Eva Feldman, only last week reiterated that the results warranted a next trial that could be the basis for regulatory approval. One of the primary things to look at in this trial is safety in the last cohort of patients who received 400,000 cells per injection and 40 injections for a total of 16 million cells. The Company believes that the more cells delivered the better and would probably go with 400,000 cells per injection and 40 injections in the upcoming trial if there is no safety issue. Do not expect every patient treated to have a favorable outcome. There will likely be a number of failures as is always the case in drug development.
- The ischemic stoke trial in China will complete the phase 1 portion of the trial in 1Q, 2015 and roll seamlessly into the phase 2/3 component. I am not sure when or if data from the phase 1 component will be released.
- The phase 1 trial of NSI-566 in chronic spinal cord injury patients has completed enrollment of the fourth and final patient. There will be a six month follow-up with topline results reported in 4Q, 2015. This trial is being performed and totally paid for by the University of California at San Diego.
- An IND is awaiting approval in South Korea for a trial of NSI-566 in acute spinal cord injury.
- The phase 2 trial of the small molecule drug NSI-189 in major depressive disorder will start in 2Q, 2015.
- A phase 1b trial of NSI-189 in schizophrenia will start in 2Q or 3Q, 2015.
- A new type of neural stem cell, NSI-523, IGF is in preclinical development for Alzheimers.
Cytokinetics
- The Company indicated that it will give an update on the potential for beginning a phase 3 trial of tirasemtiv in ALS during the quarterly conference call on February 12, 2015. I have discussed at length the probability for a phase 3 trial using slow vital capacity as the primary endpoint. See this and this This was a secondary endpoint of the phase 2b trial which failed to reach the primary endpoint of slowing progression on the ALSFRS-r scale. There was strong statistical significance on SVC overall and in all but one subgroup in the phase 2b trial. See slide 14 in the slide deck used at BIO CEO. Because the FDA has required ALSFRS-r as a primary endpoint in all previous phase 3 trials with drugs from other companies, there is a question as to whether it will accept SVC as a primary endpoint. If it does, investors are likely to conclude that there is a good probability of success in a new phase 3 that will lead to approval. I had thought that the Cytokinetics would only go forward if it received an SPA from the FDA acknowledging that the FDA would accept SVC as a primary endpoint. I asked if this would be the case and the company seemed to indicate that it would not seek an SPA. I was surprised by this..
- The COSMIC trial of omecamtiv mecarbil in chronic heart failure should complete enrollment soon and I would look for topline results in 2H, 2015. If the results are satisfactory, Amgen and Cytokinetics are likely to begin a phase 3 trial in 2016. This is a very important milestone for the drug and would trigger a sizable milestone payment.
ImmunoCellular
- The Company was scheduled to present on February 9 at 2:00 PM but cancelled. I saw the CEO Andrew Gengoes at the conference. This suggests some major upcoming announcement. It could be the plan for the phase 3 trial of ICT-107 in newly diagnosed glioblastoma.
Tagged as CUR, cytk, Cytokinetics, ImmunoCellular Therapeutics LTD, IMUC, Inc., Neuralstem, Inc., Northwest Biotherapeutics Inc., NWBO + Categorized as Smith On Stocks Blog
Thank you for attending and giving us such a speedy and comprehensive up date on what you heard….I am excited that finally we at NWBO will get some real scientific results in March….Maybe
Steven and Doc and some others, like yourself, will add clarity to what it all means…Did you go to AGEN?? There are sooooo many to attend and listen to and deconstruct…..Thank you and enjoy today…..To the tomorrows and the promises they hold in Immuno Therapy….Cheers
Perhaps the looming IMUC announcement is this morning’s S1/A offering 18mm new shares and 13mm new warrants.
Larry,
Any thoughts about the DCVax-L expansion. Multiple concerns have been made about this. Is trial resizing even a possibility considering one has already been made recently? I have heard possibly another country joining.
Has anybody noticed that Linda had mention the trial with Ovarian Cancer which has been mentioned by a few words but this time there was more time given to the trial. That makes me think expansion in Ovarian Cancer maybe a Phase III with Europe. Just my thought!! Thanks Larry for the info!!!
Women
The countries with the top 20 highest incidence of ovarian cancer in 2012 are given in the table below.
Fiji had the highest rate of ovarian cancer, followed by Latvia and Bulgaria.
About 58% of ovarian cancer cases occurred in less developed countries.
The highest incidence of ovarian cancer was in Europe and Northern America; and the lowest incidence in Africa and Asia.
Rank Country Age-Standardised Rate per 100,000 (World)
1 Fiji 14.9
2 Latvia 14.2
3 Bulgaria 14.0
4 Poland 13.6
5 Serbia 12.8
6 Lithuania 12.2
7 Montenegro 12.0
8 Malta 11.8
8 Estonia 11.8
10 United Kingdom 11.7
This certainly looks promising!!!!!!
Great stuff as usual Larry! Thanks. I listened to the CYTK webcast (my hearing is very bad) and it sure sounded as if Dr. Blum had high hopes for going forward with a Phase 3 trial for tirasmetiv. But then you (I think) asked about seeking an SPA from the FDA and as you said, Dr. Blum indicated they would probably not. You said the FDA does not enter into binding agreements, but if the FDA has not acknowledged SVC as the primary endpoint via a SPA, why would Dr. Blum be conveying such a promising outlook for tirasmetiv?
I do not think ovarian cancer would be added. For one thing, I would imagine it would almost double the trial size to test that with DCVax-L. But if Direct affects ovarian cancer than I do not see the need to do that with the DCVax-L phase 3 trial.
Linda never had a clinical data poster on DCVAX-L on advanced metastatic ovarian cancer. Ovarian cancer will not be one of the 2 to be in the Direct trial phase II. The poster with the tittle Anticipated Milestone for DCVAX- L – expansion of the program ( not Direct!!). Also the DCVAX-L Metastatic ovarian cancer 4 out of 6 patients still alive at 25,26,37, and 46 month .
Just read a posters reply from Les expansion in the trials not patients. My mistake but had a exciting moment!!
Thank you Larry and posters…..Please, if someone can, I am confused about the up-coming announcement for the expansion of “L” trials…..Not patients? Anyway, guess we will know soon…
Hope it does not extend the time to finish the trial and un-blind the results….We had that once already and it discouraged investors and gave credence to the bashers that it was not working so add more time and effort to a lost cause….So, I will wait and see and stay tuned and everything else and hope that Linda and the management team will eventually lead us to be the # 1 treatment for a wide variety of cancers in many stages of progression…That is her stated aim and here is hoping it works that way…..Thank you for any added clarity on what is coming “soon”…
The following was sent out as an 8-k
EX-99.1 2 v401089_ex99-1.htm EXHIBIT 99.1
EXHIBIT 99.1
Dear xxxxxx,
Linda’s reference to “expansion” of the Phase III GBM trial relates to an increase in the number of trial sites, not the number of patients in the trial. A key reason that we are continuing to add more trial sites, even in the late stages of the trial, is that this can only help shorten the time to completion of patient recruitment and the trial. In addition, continuing to add more sites during the trial means that more sites will be prepared in advance for commercialization.
Thanks for checking to clarify this important point, and thanks for your continuing support and inquiries,
Sincerely,
Les Goldman
Larry and Les Goldman,
Thank you for getting “expansion” clarified for us.
motley fool 2/13
ALS is a devastating neurodegenerative disorder with few treatment options beyond supportive care. So a drug that shows any form of clinical benefit could stand a chance of gaining a regulatory approval.
Tirasemtiv’s value proposition as an ALS treatment, though, doesn’t appear all that tantalizing. The total ALS market is expected to decline to $70 million by 2019, and tirasemtiv doesn’t appear to hold any real promise as a game-changing drug at this point.
Given the sudden rise in its share price and minimal cash position (roughly $83 million, per today’s earnings release), this microcap biotech looks ripe for a large secondary offering. As such, you might want to exercise caution on the back of this clinical trial update and earnings release.
I marvel at how idiots like this can find a forum to publish this garbage.
Hi and I wonder if their expansion into Canada is worth you commenting on??? I just hope they will tell us when enrollment for :L” is completed…..What do think of that question?? will they???
I am standing by and waiting for the report that is to come out of Europe in March….Wonder what that will say??? I would love to see them begin the “D” trial in Germany, of course….Can’t wait for the manufacturing plant in the UK to be completed and then we can go ahead and get that place approved and then submit part 2 for the PIM designation….So many shots on goal….I wonder what AF and JF are saying….I hope you keep warm and keep the typewriter going and keep you vital data mining operation going for us prospectors….cheers
Larry, you personally an your considerable effort an the quality of your Work are Exceptional ! I had the good fortune to be in the Ranks of those persons with the above mentioned character for a Time….Outstanding effort an dedication to Quality are shining examples of rare gifts ! Thank you for your remarkable skill an talent in defining an covering such lengthy conferences an meetings…an then to elaborate the details so precise..! thanks again . C..