Nektar Announces Topline Data from Human Abuse Potential Study for NKTR-181, a First-in-Class Investigational Opioid to Treat Chronic Pain NKTR-181 shows significantly less abuse potential compared to oxycodone Analyst C

Nektar Announces Topline

Data from Human Abuse Potential Study for NKTR-181, a First-in-Class Investigational Opioid to Treat Chronic Pain

NKTR-181 shows significantly less abuse

potential compared to oxycodone

Analyst Conference Call and Webcast Today

at 5:45 a.m. PDT/8:45 a.m. EDT

SAN FRANCISCO, July 18, 2017 /PRNewswire/ -- Nektar

Therapeutics (NASDAQ: NKTR) announced positive topline results from an oral Human Abuse Potential (HAP) study of NKTR-181,

a first-in-class opioid analgesic. NKTR-181 is a new chemical entity (NCE) that is the first full mu-opioid agonist molecule

designed to provide potent pain relief without the high levels of euphoria that can lead to abuse and addiction with standard opioids.1

NKTR-181 is the first analgesic opioid molecule to exhibit reduction in specific CNS-mediated side effects, like euphoria, through

the strategic alteration of brain-entry kinetics. The U.S. Food and Drug Administration (FDA) has granted the investigational

medicine NKTR-181 Fast Track designation for the treatment of moderate to severe chronic pain.

The NKTR-181 HAP study was designed to confirm

and assess the relative oral abuse potential of NKTR-181 at its maximum analgesic or therapeutic dose (400 mg) and at a supratherapeutic

dose (3 times to 12 times greater than its analgesic dose range of 100 mg to 400 mg) compared to common therapeutic doses of a

Schedule II opioid, oxycodone.

"Today's opioid abuse epidemic has created

a pressing need for a better pain medicine that does not possess the euphorigenic qualities of conventional opioids," said

Ivan Gergel, MD, Senior Vice President and Chief Medical Officer of Nektar. "It is clear from our new study results

that NKTR-181 is highly differentiated in this respect from oxycodone, which is a choice drug of abuse. Further, and critically

important in the context of this public health emergency, NKTR-181's less rewarding properties and strong analgesia are inherent

to its novel molecular structure and independent of any abuse-deterrent formulation. Many patients do not receive adequate

pain relief because they fear taking conventional opioids, including abuse-deterrent formulations, because of their potential for

abuse and addiction. We believe NKTR-181 is a transformational pain medicine that should significantly advance the treatment

of chronic pain and could be a fundamental building block in the fight against prescription opioid abuse. We are committed to bringing

this new pain treatment to patients and physicians as quickly as possible."

Opioids act on specific receptors in the brain

to provide pain relief, but they also target the dopamine reward system in the brain to produce euphoria and other psychoactive

effects, which leads to addiction and abuse.1 Brain imaging studies have shown that the faster a euphorigenic

drug enters and leaves the brain, the stronger are its reinforcing effects.2 In 2014, nearly 2 million Americans either

abused or were dependent on prescription opioid pain relievers.3 Opioid abuse is a growing epidemic in the U.S.,

with one in five Americans who say they have a family member who has been addicted to prescription painkillers.4

"Getting very high, very fast, is a mark

of conventional high-risk, abused opioids," said Jack Henningfield, PhD, vice president at Pinney Associates and adjunct

professor at The Johns Hopkins University School of Medicine. "NKTR-181 represents a meaningful advance in the treatment

of pain as the first opioid analgesic with inherent brain-entry kinetics that avoids this addictive quality of traditional opioids.

This prevents the rapid 'rush' that abusers seek during the critical period immediately after dosing. Importantly, these properties

of NKTR-181 are inherent to its molecular structure and are not changed through tampering or route of administration."

In March 2017, NKTR-181 completed a Phase 3

efficacy trial (SUMMIT-07) in 610 patients with moderate to severe chronic low back pain who were new to opioid therapy (opioid-na ve).

SUMMIT-07 evaluated four analgesic doses of NKTR-181 (100 mg, 200 mg, 300 mg and 400 mg). Patients in the trial achieved

an average pain score reduction of over 65% (from 6.73 at screening to 2.32 at randomization) during the dose titration period.

The primary efficacy endpoint of the study demonstrated significantly improved chronic back pain relief with NKTR-181 compared

to placebo (p=0.0019). Key secondary endpoints of the study also achieved high statistical significance. The study demonstrated

that NKTR-181 had a favorable safety profile and was well tolerated.

HAP Study Design and Objectives

HAP studies are clinical studies that help assess the relative abuse potential of a medicine. The NKTR-181 HAP study was

a randomized, double-blind, placebo-controlled, six-sequence crossover study evaluating the relative oral abuse potential of NKTR-181

relative to the Schedule II opioid oxycodone in healthy non-dependent recreational drug users experienced in the oral abuse of

opioids who can identify drug effects that are relevant to abuse risk assessment. Subjects (n=54) were randomized to one

of six test sequences, in each of which they received a single dose of one of the six study drugs:

NKTR-181 400 mg (highest efficacious dose established in

the Phase 3 efficacy trial);

NKTR-181 600 mg (a dose of 1.5 to 6 times greater than

the efficacious dose range established in the Phase 3 efficacy trial);

NKTR-181 1200 mg (a supratherapeutic dose of 3 to 12 times

greater than the efficacious dose range of 100 mg to 400 mg established in the Phase 3 efficacy trial);

Moderate therapeutic dose of oxycodone at 40 mg

High therapeutic dose of oxycodone at 60 mg

There was a five-day washout period between

each treatment. NKTR-181 doses and its matching placebo were administered as oral tablets. Oxycodone HCl doses were administered

as over-encapsulated oral tablets.

The study evaluated effects that are predictive

of abuse potential with opioids for all doses in the study. The HAP trial was powered to detect a relative peak (Emax*) drug

liking score difference between oxycodone at 60 mg and NKTR-181 at 1,200 mg. Liking was based on a subject-reported 100-point

bipolar liking/disliking visual analog scale (VAS), which is a standard measure of abuse potential in HAP studies. Key secondary

endpoints were Area Under Effect for Drug Liking in the first 1, 2 and 3 hours after dosing as well as retrospective subject-reported

unipolar VAS ratings for Drug High and bipolar VAS ratings for Take Drug Again.

Primary Endpoint of Drug Liking:

NKTR-181 400 mg had a significantly lower rating of peak

(Emax) liking compared to oxycodone 40 mg (62.0 vs. 76.6, p<0.0001).

NKTR-181 400 mg had a significantly lower rating of peak

(Emax) liking compared to oxycodone 60 mg (62.0 vs. 81.5, p<0.0001).

NKTR-181 600 mg had a significantly lower rating of peak

(Emax) liking compared to oxycodone 40 mg (67.9 vs. 76.6, p<0.0001).

NKTR-181 600 mg had a significantly lower rating of peak

(Emax) liking compared to oxycodone 60 mg (67.9 vs. 81.5, p<0.0001).

NKTR-181 1200 mg had a significantly lower rating of peak

(Emax) drug liking compared to oxycodone 60 mg (76.7 vs. 81.5, p=0.0071). This dose was not statistically different from oxycodone

The peak liking score for NKTR-181 400 mg oral

tablet in this study confirmed the same peak liking score for NKTR-181 400 mg oral solution evaluated in the company's prior HAP

study (62.0 vs 62.3**).

Secondary Endpoint of Area Under Effect

(AUE) for Drug Liking Following Dosing (0-1 Hours, 0-2 Hours, 0-3 Hours):

NKTR-181 400 mg had significantly lower AUE for all timepoints

compared to both oxycodone 40 mg and 60 mg (p<0.0001).

NKTR-181 600 mg had significantly lower AUE for all timepoints

compared to both oxycodone 40 mg and 60 mg (p<0.0001).

NKTR-181 1200 mg had significantly lower AUE for all timepoints

compared to both oxycodone 40 mg and 60 mg. For AUE (0-1 Hours), p=0.0002 and p<0.0001, respectively; for AUE 0-2 Hours, p=0.001

and p<0.0001, respectively; for AUE 0-3 Hours, p=0.0396 and p=0.0003, respectively).

Secondary Endpoint of Drug High:

NKTR-181 400 mg had significantly lower ratings of peak

(Emax) Drug High compared to both oxycodone 40 mg and 60 mg (p<0.0001).

NKTR-181 600 mg had significantly lower ratings of peak

(Emax) Drug High compared to both oxycodone 40 mg and 60 mg (p<0.0001).

NKTR-181 1200 mg had a significantly lower rating of peak

(Emax) Drug High compared to 60 mg oxycodone (p=0.0071).

The peak Drug High score for NKTR-181 400 mg