Interesting question. And the conclusion that vaccines don't work seems obvious on the surface. After all, there seems to be a lot of painful evidence, right? But do keep this in the back of your thinking... it may be that vaccines simply do not work by themselves. The company has, from the beginning, held that the combination of vaccines coupled with checkpoint inhibitors is their goal. Throwing this vaccine baby out with the bathwater may be a scientific mistake.
The phase II also had around 59% of the patients respond to at least one antibody parameter from the vaccine. The patients who responded enjoyed higher survival as a group. The non-antibody responders together as a group had about 17 months median survival. I would submit that the control patients for phase III will most probably be in the non-responding category.
The bar was still pretty high for logrank at 2nd interim.
Consider the following example
Months 12 24 36 48
Trial OS 92% 75% 58% 50% This is a pretty decent result.
Ctrl OS 70% 50% 38% 30% this reflects a 24 month MOS
The above scenario would have shown around a 22% advantage at 33.5 months (2nd interim) The requirement for a stop at that point was 35
These same survival numbers would produce a 34% advantage at 46 months follow up (final look if last month) 20% required for success.
The result is getting better while at the same time, the bar of success is getting lower.
I ran a quick calculation just to see using the following parameters.
Trial: 12 mo = 90%, 24 mo. = 77% 36 mo = 65%, 48mo = 51%
Ctrl: 12 mo = 70%, 24 mo = 50%, 36 mo = 35%, 48mo = 25%
At the final look, assuming end of April, I got a 42% advantage.
BUT INTERESTINGLY, this same set of OS numbers would only produce 31% advantage at the 333rd event interim (assuming 33 months follow up in Feb 2015.
The stopping point is when 442 events are reached. This is in total number. We will not know how many events occurred from each arm until the analysis is complete/presented.
ah, you are correct. I must have read the wrong number. 48 months then is in the mid to low 20s range then.
Around the end of this month, our middle (median) patient crosses 48 months since surgery. Our youngest patient will be in for 33 months. Historically 48 month survival for this indication has been in the mid teens (15% range) while 36 month has been around 20%. We still have around 40% of IMPRESS patients alive.
So.... is this a block buster result or did standard of care suddenly more than double? You decide.
I have already demonstrated why/how the trial would have continued at both previous interims.
Based on estimated monthly events, and based on a sliding attrition rate (we don't have as many living patients as we did last year so the rate will naturally slow on a percentage basis) and throw in a small reduction for curve flattening, I put the 442nd event to be somewhere around the end of May.
That also places combined median survival (for the overall trial) at 33/34 months, occurring in May/June of last year.
The Defense Department continues to support NLNK's anti-biological vaccine efforts.
Defense Threat Reduction Agency (DTRA) of the United States Department of Defense has awarded a subsidiary of NewLink Genetics a $2.8 million base contract with potential future options totaling $6.3 million to support the development of vaccines against filovirus species including Marburg and Ebola Sudan viruses, which could be combined with Ebola Zaire virus in a multivalent vaccine formulation or vaccination schedule
Two things have happened since the interim analysis at 333 events. First, the success bar is lowered by 1/3. The 2nd analysis required demonstration of ~35% advantage to be significant and stop the trial. This final look will require approximately a ~20% advantage.
At the same time, the follow up has increased by ~14 months, or about over 40%.(so far) This increases the amount of real estate that can be calculated by the log rank analysis because median follow up has increased. (to the right)
So literally we are measuring quite a bit more area to find quite a bit less advantage. Since curves in immunotherapy trials tend to separate during the last phases of the trial, the real estate on the right side of the chart is VERY IMPORTANT to the log rank number!
My understanding is that they application date starts clock. Protection duration depends on type of patent, but generally 20 years or 17 years (I think). Companies employ strategies to get maximum protection over time. Generally, they don't disclose this stuff until they really need to.
Here is another... perhaps more relevant
US 9,090,643 B2
Enhanced immunogenicity of tumor associated antigens by addition of alphagal epitopes
Mario R. Mautino, Ankeny, IA (US); Nicholas N. Vahanian, Polk City, IA (US); Won-Bin Young, Pittsburgh, PA (US); Gabriela Rossi, Ankeny, IA (US); Charles J. Link, Clive, IA (US); and Firoz Jaipuri, Ames, IA (US)
Assigned to NEWLINK GENETICS CORPORATION, Ames, IA (US)
Filed by NewLink Genetics Corp., Ames, IA (US)
Filed on Dec. 17, 2012, as Appl. No. 13/716,569.
Application 13/716,569 is a continuation of application No. 13/173,692, filed on Jun. 30, 2011, granted, now 8,357,777.
Application 13/173,692 is a continuation of application No. 11/977,203, filed on Oct. 24, 2007, granted, now 7,998,486, issued on Aug. 16, 2011.
Claims priority of provisional application 60/862,840, filed on Oct. 25, 2006.
Prior Publication US 2013/0178613 A1, Jul. 11, 2013
WO2014186596 CORRELATES OF EFFICACY RELATING TO TUMOR VACCINES
WIPO published November 20, 2014 International filing date was 5/15/2014
What?, is it already time for the monthly planned sell ? Wow, the months just fly by.
*runs back and forth across the screen yelling THE SKY IS FALLING!!! just for effect*
ok, back to work
The Annual Meeting will be held on Friday, May 20, 2016 at 9:00 a.m. local time at the offices of NewLink Genetics Corporation, 2503 South Loop Drive, Suite 5100, Ames, IA 50010
I agree... Read me again, the north of Ben Franklin was just the dimension of the gap up the next morning. LOL The value of the company is way more.
IMPRESS positive outcome would validate the entire hyperacute line currently covering 5 different cancers and an additional number of develop able solid tumors beyond that. Short interest is thick and current value is quite a bit lower than historically. How far and how fast a sudden shortage of stock would drive this is anybody's guess but north of $100 would be the probable gap.
The company has stated, (rather emphatically) that there would be no press release until the analysis is complete and results are known.
The agreement was two-fold. They modified their existing agreement (Indoximod) to include pro-drugs related to Indoximod, and they secured the rights (worldwide) to the new PTEN pathway checkpoint inhibitor. Both Indoximod and PTEN came out of Dr. David Munn's lab in Augusta, GA.
Looking at Baird's valuation for the company compared to other analysts. They basically are pronouncing Hyperacute program as a lottery ticket, forgetting Indoximod completely and counting the partnered IDO/TDO at half it's milestone values. Well, that's pretty dismal but look at it another way
The way Baird sees it, you can buy IDO for your $17 street price and get $7 cash plus Hyperacute program for free.