NKTR-214 ASCO Slide Deck

Here is the slide deck from this evenings NKTR-214 ASCO presentation for review:

http://www.nektar.com/application/files/1815/2797/2670/NKTR-…

The patient response data cut is from May 29th, so this is the current up to date data on PIVOT.

My prelim review is that all three malignancies (stage IV melanoma, Stage IV RCC (renal), and stage IV NSCLC (Nonsmall cell lung CA) show deepening response rates over time, spread over the cohort (which is relatively small, 11, 14, and 5 patients respectively). In fact, one patient in the RCC cohort and one patient in the melanoma cohort have achieved complete clinical remission and are therefore off study. This is as close to cured as you can get. There are too few patients in the NSCLC cohort to make a statistically significant judgement as whether to proceed to Phase 2. This is probably only a matter of time.

Note that not all patients are responders, with a few progressing despite therapy, but the majority show deepening response over time. Several of the patients have showed diminished tumor bulk of near 100%, with others over 50%, with very few patients coming off therapy due to adverse effects.

Now enrolling and expanding phase 2 for RCC, melanoma, and urothelial CA…

Jack

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And here is a link to the press release with highlights…

http://ir.nektar.com/news-releases/news-release-details/prel…

Jack

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The conclusion slide…

• 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).
• 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 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.

I don’t see this as a “binary event” for NKTR… but I do see it as good news that 214 is being recommended to move on with continued studies and is showing positive results. And for the patient that had a complete recovery… they’ll consider 214 their miracle. While investing in this stock, I like imagining how these patients helped must feel.

Since folks seem to respond better the longer they are on this, I wonder they continue these treatments for longer duration.

Mark

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I tried reading the data slides in the slide desk, I really did, but they just seemed like a jumble of abbreviations that I couldn’t make sense of and couldn’t wade through. (I’d love it if someone could put the results into English words for all of us).

On the other hand, the progression of illness graph slides told a great visual story. They showed patients getting better and tumors shrinking, and shrinking more over time, with some cured entirely, in the vast majority of patients (eyeballing it). And yes there were a few patients who did not respond, but these are cancer patients after all, and if I’m reading the graphs correctly, most of those tumors were staying the same size instead of rapidly progressing. And the CT scan pictures gave the same story. Tumors were shrinking. Okay! Sounds good! Looks good! But I do wish I knew what all the letters and abbreviations meant.
Saul

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Hi Saul,

Yeah, I agree that the jumble of acronyms and jargon makes little sense to me either. With that said, here are my observations:

  1. as more data come available, more and more patients show improved response; this is happening with multiple studies for multiple tumor types

  2. latest dataset is small, but clinical trial continues to progress positively for several cancers

  3. some patients cured

  4. adverse effects are not bad and very few patients discontinue therapy (although the one or two patients who were “cured” discontinued!!

  5. all trials being continued (this is very positive and significant)

  6. based on the results, one indication will be advancing to Phase III in Q3

  7. Friday’s stock price was up big so I wonder if someone knew something about the data

Despite not knowing the words, I can infer that these data updates are VERY positive. I expect the stock to be up again on Monday. Not selling any of my shares. I had increased my position over the past few weeks. Currently at 8.9% of my portfolio and not selling any.

Chris

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Despite not knowing the words, I can infer that these data updates are VERY positive… Not selling any of my shares. I had increased my position over the past few weeks. Currently at 8.9% of my portfolio and not selling any.

Thanks Chris, I inferred the same thing, and I’m at 8.15% myself.
Saul

Hi Chris,

7) Friday’s stock price was up big so I wonder if someone knew something about the data

I think their filing of a new drug application for NKTR-181 caused the stock price increase on Friday. See from a Seeking Alpha article below:

On May 31, 2018, Nektar disclosed that the company filed the new drug application (“NDA”) for NKTR-181 (as a first-in-class investigation to treat chronic low back pain in adult patients new to opioid therapy). The market for back pain is gargantuan. Back pain is the most common reason patients seek a physician. With 19% of the U.S. population suffering from some type of persistent back pain, the potential approval can procure gargantuan profits.

https://seekingalpha.com/article/4179029-rounds-report-nekta…

Also, some of the comments in the SA article were less positive on the ASCO data with some expecting a drop on Monday. I guess we’ll find out soon.

Long NKTR Jan 2019 70 calls

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A few thoughts, FWIW.

as more data come available, more and more patients show improved response

If I understand correctly, you mean that as time goes on the response rate increases. If so, this is entirely to be expected given the mechanism of action of checkpoint and IL-2.

some patients cured

Not sure I see any “cures”. Way too early to know.

adverse effects are not bad

Agree. Appears to be in line with previous studies.

) all trials being continued (this is very positive and significant)

Not surprising, so neutral, IMO.

based on the results, one indication will be advancing to Phase III in Q3

For sure.

Friday’s stock price was up big so I wonder if someone knew something about the data

The slide deck is really not that substantially different from the abstract itself, so not sure that Friday’s price was driven by this. I assumed it was because of NDA filing of 181.

can infer that these data updates are VERY positive

Certainly encouraging that there is no negative news, but overall, their ORR and DCR are very comparable to Keytruda in melanoma and Keytruda plus TK inhibitors in RCC. By no means bad news, but nothing yet to suggest that Opdivo plus 214 is superior to others. That said, they still have option to work with Keytruda (which to me is very strange in and of itself), so that is a potential positive.

expect the stock to be up again on Monday

No idea what the stock price will do in reaction to these data. Wouldn’t be surprised if it rose or fell by 10% or didn’t move at all.

Cosmid

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I think their filing of a new drug application for NKTR-181 caused the stock price increase on Friday.

But it was known that they would file the NDA in April. Management said it during the last conference call.

Chris

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But it was known that they would file the NDA in April. Management said it during the last conference call.

But Chris, they still “had” to get “permission” from the FDA to file the NDA. They apparently got it, so that this was an indication that approval is more likely than not. I’d guess.
Saul

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But it was known that they would file the NDA in April.

Saul is right; filing is always viewed more positively that saying you will file.

The next step will be the FDA announcing that they have accepted the filing. They do a cursory review of the application to be sure that the filing is complete and in-line with what NKTR had proposed in the initial IND application. Barring a major screw-up, I think it is a fait accompli that FDA will accept the filing.

Cosmid

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I tried reading the data slides in the slide desk, I really did, but they just seemed like a jumble of abbreviations that I couldn’t make sense of and couldn’t wade through. (I’d love it if someone could put the results into English words for all of us).

On the other hand, the progression of illness graph slides told a great visual story. They showed patients getting better and tumors shrinking, and shrinking more over time, with some cured entirely, in the vast majority of patients (eyeballing it). And yes there were a few patients who did not respond, but these are cancer patients after all, and if I’m reading the graphs correctly, most of those tumors were staying the same size instead of rapidly progressing. And the CT scan pictures gave the same story. Tumors were shrinking. Okay! Sounds good! Looks good! But I do wish I knew what all the letters and abbreviations meant.

I’ll try to post some thoughts during the next week, but I’m busy at work, so I’m not sure I will get around to it. I’ll try to overlay this onto the historic Opdivo data in RCC and Keytruda in melanoma to see if they are seeing any signs of synergy (data set is too small to make a conclusion).

This is kind of a “steady as she goes” data. A pessimist would say that it is to be expected and these results are priced into the stock. An optimist would say that it is going great, buy more NKTR! No idea how this will affect the stock tomorrow.

What is encouraging is that a melanoma patient converted into a CR, and one more reaching -100%, two more approaching -100%. In RCC, 2 patients reached -100%.

Some nice MOA slides near the end that is consistent with the proposed therapeutic hypothesis of -214.

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Either NKTR did a bad job explaining their results or we’ve just got a lot of bad journalism going on (maybe both). I see a lot of lazy articles written that state that as NKTR added patients to each of their studies, that the response rates dropped significantly and that this is a BAD thing.

Case in point from here: https://www.statnews.com/2018/06/03/asco-bristol-nektar-comb…
If anything, the presentation raised more doubts.
In a group of 13 melanoma patients, treatment with NKTR-214 and Opdivo demonstrated a impressive tumor response rate of 85 percent. That means 11 of the 13 patients responded.
But then the companies enrolled another 15 melanoma patients, and the response rate dropped. In the update, 14 of the now 28 treated patients (50 percent) showed significant tumor shrinkage. That means only three of the 15 added patients responded — a concerning drop in the efficacy of the NKTR-214-Opdivo combination.

As many on the board have pointed out, the response rate typically DEEPENS over time. So of course, when new people are added, we’d expect the response rates to drop. Significantly!

To his credit the author does state that

Bristol and Nektar defended the results, saying tumor responses are expected to get better over time. The patients enrolled later in the study have not been followed long enough, but when they are, the companies expect more tumors to shrink, boosting the response rates.

…I just wish he had made a much bigger point to focus on the above statement rather than all the time spent on worsening response rates which DONT account for time!

I wouldn’t be surprised at all to see the stock drop on Monday with all the controversial headlines then creep back up to normal levels as analysts realize there is no need for alarm over this.

-AJ

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Either NKTR did a bad job explaining their results or we’ve just got a lot of bad journalism going on (maybe both).

My vote would be neither. NKTRs slide deck includes early enrollments. If they don’t include these, they would be accused of cherry-picking. Since they did, some (wrongly) interpret this as a lower response rate. The author of the Stat piece isn’t taking sides. He is a veteran journalist in the biotech sector who is reporting the buzz he is getting from people attending ASCO. Like it or not, that is what the buzz is. It will be sorted out in the fullness of time.

and Nektar defended the results, saying tumor responses are expected to get better over time. The patients enrolled later in the study have not been followed long enough, but when they are, the companies expect more tumors to shrink, boosting the response rates.

And their defense is right, IMO. A few months back I suggested that 214 gets no credit for late responders as it is a characteristic of the mechanism of the drug. By the same token, the appearance of a lack of early responders is not a valid criticism because the mechanism predicts it.

Cosmid (no position)

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And regarding the dropout rate: 9 patients were not evaluated because the trial already met its efficacy endpoint.

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