I understand that:
IBG = Informed Best Guess
CANCER:
Although it may be Feb. before dosing is complete for the 12 combo patients in India, MRI studies will be done frequently to measure tumor response throughout the 8 week treatment program, not just 4 weeks after dosing completes. This is important because it will allow PPHM to start selecting, as early as January, which of the three tumor types -- breast, lung or pancreatic -- should be the focus of the first Ph II trial.
As SK said in the Sept. CC, the Company is preparing to “move directly” into larger Ph II/III type trials once the Indian combo trial is complete. The reason why tumor response, i.e. efficacy, was not included as a formal endpoint of the 12 patient India combo study was to allow Ph II to get started faster. You can’t start Ph II in US or India until all of the Ib endpoints have been fully evaluated.
The next major strategic decision the Company faces is to select the cancer type, i.e. breast, lung or pancreatic, for its initial Ph II trial. The FDA will not allow Ph II to be done as an all-comers trial.
In my IBG, shortly after January MRI scans start revealing which tumor type is most responsive to Bavi plus chemo, negotiations with a BP collaborator will be finalized. My IBG is that the Company is already discussing collaboration terms with the BPs behind docetaxel, gemcitabine and carboplatin/paclitaxel.
The cost of Ph II/III trials similar to those done for Avastin (whose development path we are imitating) is enormous. Such a trial could have as many as 5-10 arms and each arm could have 100-200 patients. In India the cost of each patient will be around $15K-20K and twice that amount in the US. Thus an Indian arm with 150 patients will cost around $3M and the same study arm done in the US will cost around $6 million. The good news is that the FDA will count the patients done in an Indian arm just as if they were done in the US. So if the total Ph II/III has eight arms and five are done in India and three in the US, the total cost of this Ph II/III study could be around $33 million (3x$6M plus 5x$3M).
My IBG is that the cost of PPHM’s first Ph II study will be paid for through a collaboration with the BP that has the greatest stake in protecting its chemo market share in the tumor type PPHM decides to go after. Contrary to views I have expressed previously, it now seems the investment banking route will be too expensive (heavy warrant coverage would be required) and third party licensing of Cotara for GBM may not make sense for the reasons discussed below. Clearly a financing in the $40M-$45M range (i.e., $33M for Ph II/III and another $7M-$12M for general working capital needs) is way beyond the reach of UU or any other PIPE player.
In my IBG, based on MRI tumor scans done in Dec and Jan, the Company will finalize a BP collaboration in Feb and file the Ph II/III with the FDA the same month and start dosing patients in April. The BP who is willing to run lock-step with PPHM in achieving this aggressive schedule will win Bavi rights for its primary cancer market at a much lower cost than other BPs will have to pay down the road for licensing rights in their respective cancer markets. It’s also possible PPHM could announce two Ph II/III studies starting roughly the same time, each supported and funded by a separate BP collaboration.
News of this BP horse race could leak out in Jan or Feb in advance of a PR of top line data from the 12 patient Indian combo trial. If several BPs are competing for the same collaboration, there is likely to be an industry buzz in addition to the buzz that may come out of the Indian medical community.
COTARA FOR GBM
PPHM is confident they have a winner here. The latest results show Cotara extending survival time in 3rd and 4th relapse patients by twice as long as Temozolomide in 1st relapse patients!!! If these results are repeated in the current 40 patient Indian trial then PPHM may have an opportunity to market the drug directly without licensing to BP. This is possible because the advantages of Cotara over SOC are so huge that all the brain oncologists (a relatively small group) would switch to Cotara without need for PPHM to develop an expensive marketing program. Temozolomide is a $600M annual global market. The margins on MABs are so great that most of this would go straight to the bottom line.
Personally, I very much like the notion that PPHM may do its own direct marketing of Cotara for GBM. Once collaborations with BP are announced for Bavi Ph II trials and/or it becomes clear Bavi will be a player in the HCV market, it should be easy to raise capital north of $5/sh to pay for completion of Ph II/III Cotara GBM studies in India. Approval of Cotara for GBM in India may not require as many study arms as would be the case in the US. The Indian docs are VERY excited about Cotara. Once it gets approved in India, approval on other continents would follow quickly.
HCV
One of the viable options for administering Bavi is to give it like a booster shot once a month to re-invigorate the immune system.
Interferon by itself as a monotherapy achieves only a 1.0-1.5 log reduction in viral load. When combined with Ribavirin this increases to 2.0 log reduction. Given that Bavi has no toxicity, if the repeat dose data comes in next month showing a reduction anywhere from 1.0-2.0 logs for Bavi as a monotherapy, Bavi will have earned a secure place in the pantheon of new HCV therapies.
Combination trials with Ribavirin are likely to start before a trial focused on naïve patients. Naïve patients are much harder to find and trial would take much longer to enroll.
HIV
Lots of meetings and excitement from third parties at AASLD about Bavi’s potential for treating HIV-HCV co-infected patients. Apparently there is a huge, unmet medical need in this patient population since co-infected patients often end up not being able to receive either HCV SOC or HIV SOC. In my IBG, the Company will start its own Bavi Ph I trial in co-infected patients (without a large institutional collaborator like Duke) sometime in the next month or two using docs who got excited about Bavi at AASLD.
Duke / Gates are running in their own direction to develop Bavi as an HIV vaccine and that work is going just fine. In my IBG there will be a publication out of Duke on this work in Q1.
CMV
In my IBG, CMV clinical trial is also imminent. Demand for CMV therapy in connection with liver transplants is huge. A CMV trial and a co-infected HIV trial are both very close.
Dr. Thorpe’s presentation on Dec. 12 will probably not be webcast but release of new US cancer and HCV clinical data by way of a PR the same week is entirely possible.
All longs should get ready for a feast. The table is set. The side dishes are all coming together and, in my IBG, the turkey itself -- a Ph II collaboration with BP for breast, lung or pancreatic -- is almost on the table.
Let’s be Thankful.
