All,
I’m in Montana, and the sun is setting, albeit very slowly, over a particularly placid Flathead lake. I have a brew, and I am amazed that a post I made a few mornings ago had such an impact. Thank you all for the kind words, but that post was little payback for the troves of knowledge and ultimately market beating returns that I have been blessed with as a recent member of this board community. As such, I felt an obligation to listen to the Jefferies Healthcare conference webcast from this afternoon given by NKTR’s chief scientific officer.
Here is a link to the webcast. It is 25 minutes long and is excellent for anyone with an interest in what this company is doing and trying to do:
http://wsw.com/webcast/jeff113/nktr/
Short answer, its all good, and we have interpreted their data correctly.
Here are my notes from the webcast: the long answer.
Jonathan Zeleski, the chief scientific officer first summarized their pipeline:
Immuno-Oncology (NKTR-214, NKTR-262, NKTR-255), Immunology (NKTR-358), and Chronic Pain (NKTR -181)
He briefly summarized the development and current status of NKTR-181:
• 15 clinical trials over 2200 subjects including efficacy, safety, and abuse potential evaluation.
• Met with FDA twice pre-NDA to finalize NDA package.
• Actively evaluating potential licenses to commercial partners or other strategic structural alternatives.
I think this is a fait accompli for approval.
He then spent the majority of the time on NKTR-214. These are the main conclusions about the current state of NKTR-214:
• Pre-specified efficacy criteria were achieved in 1L melanoma, 1L renal cell carcinoma and 1L cisplatin-ineligible urothelial carcinoma which support the evaluation of NKTR-214 plus nivolumab in registrational trials.
• NKTR-214 in combination with nivolumab showed encouraging anti- tumor activity with notable ORR in PD-L1 negative patients (42% melanoma, 53% RCC, 60% urothelial).
• NKTR-214 in combination with nivolumab at the RP2D was well tolerated with a low rate of Gr3+ TRAEs including immune mediated AEs.
• Robust translational data confirm rationale for activation of the immune system in the tumor microenvironment with a conversion of PD-L1 negative tumors to PD-L1 positive on treatment.
• Ongoing enrollment in PIVOT-02 continuing for additional tumor types in I-O naïve and refractory settings.
The science behind NKTR-214:
• Biased signaling to CD122 receptors (IL-2Rbg).
• Activates CD8 T-cells and NK cells.
• Proleukin (native IL2) first drug approved for renal cell carcinoma treatment several decades ago, but very toxic.
• NKTR-214 is polymer conjugated (PEGylated) IL-2 in a way biased toward CD122 receptor.
• Its use results in a 30 fold elevation in CD8 T-cells and 26 fold increase in PD-1 expression on these CD-8 T-cells (blocking these PD-1 receptors is the target of Keytruda and Opdivo).
BMS NKTR Partnership:
In partnership with BMS, they are evaluating 9 different tumor types over 20 indications in over 15,000 patients. NKTR will bear anywhere from 22 to 32% of the cost of drug development, not to exceed 125M per year.
Review of PIVOT Phase I/II data:
• Seeing strong responses in PD-L1 negative patients in that the doublet of NKTR-214 and Opdivo converts tumor from PD-L1 negative to PD-L1 positive (this is the first time this has been scientifically demonstrated).
• This has occurred in over 50% of patients with PD-L1 negative tumors.
• These PD-L1 positive patients, either native, or converted, showed greatest clinical benefit.
This an important distinguishing feature of the therapy, that it can convert tumors to becoming responders.
They added a slide called a Swim lane plot that segregates patients by time on therapy. These are clarifying slides (in response to the 40% stock haircut) that allow the N1 patients to be seen as distinct from the N2 patients, and clearly demonstrate that the longer on therapy, the deeper the response rates. I hope this alleviates the analysts fears, but who knows.
In Renal cell and bladder CA, they have several PD-L1 negative patients responding, with some achieving complete responses. Across all tumor types, they have had only one relapse. They are also seeing very strong responses with NSCLC, albeit with an small phase I cohort.
NKTR safety profile is strong with patients now on continuous three week interval dosing for over a year.
Hope all this helps.
For full disclosure, I doubled my NKTR position at 54 and change. I do not know how the share price will respond, but I do think NKTR’s science is sound and its clinical data robust and meaningful to patients. I have heard much consternation about the success of Keytruda and how that must hurt NKTR’s prospects. I think the entire opposite because once Keytruda and NKTR-214 get together (PROPEL trial), I anticipate further synergistic clinical response. I think BMS was wise to corner NKTR-214, at least for a time, for certain high profile malignancies, and I think it was wise for NKTR to partner with BMS to get access to cash and BMS’s clinical trial expertise to get NKTR-214 to market. Once on market, it is my anticipation that NKTR-214 will play a role in nearly all Immuno-oncology oriented cancer therapies.
Jack