Nektar Therapeutics (NASDAQ: NKTR) today
announced three presentations at the 61st American Society of Hematology (ASH)
Annual Meeting & Exposition for its IL-15 agonist and investigational candidate, NKTR-255. Data were presented from a number of preclinical studies conducted in collaboration with researchers from the Dana Farber Cancer Institute and the Fred Hutchinson Cancer Research Center. NKTR-255 is an interleukin-15 (IL-15) receptor agonist, which is currently being evaluated in a Phase 1 clinical study in patients with multiple myeloma (MM) and non-Hodgkin"™s lymphoma (NHL). NKTR-255 is designed to work by selectively targeting the IL-15 pathway to expand both natural killer (NK) cells and memory CD8 T cell populations.
"The preclinical data presented at ASH demonstrate NKTR-255"™s promise in hematological malignancies through its potential to restore both NK cell and memory CD8 T cell compartments in patients," said Loui Madakamutil, Ph.D., Senior Vice President and Head of Discovery and Research at Nektar Therapeutics. "In studies presented by the laboratory of Dr. Nikhil Munshi at Dana Farber, NKTR-255 enhanced the number and function of NK and CD8+ effector memory T cell populations in peripheral blood and bone marrow from patients with multiple myeloma and, also increased expression of activating receptors found on those NK cells. Separately, researchers from the laboratory of Dr. Cameron Turtle at Fred Hutchinson demonstrated NKTR-255 prevented tumor growth and increased survival of CAR T cells when added to a CD19-targeted CAR T cell regimen in models of B cell lymphoma. This preclinical data reinforces the basis of our ongoing clinical trial evaluating the potential of NKTR-255 in patients with multiple myeloma and non-Hodgkin"™s lymphoma."
Details of the preclinical data presentations at ASH are as follows and are available on the scientific section of Nektar"™s website at http://www.nektar.com/science/scientific-posters:
Abstract 2866: "Combination of NKTR-255, a polymer conjugated human IL-15, with CD19 CAR T cell immunotherapy in a preclinical lymphoma model," Chou, C., et al. (This study was conducted in collaboration with the Turtle Laboratory in the Fred Hutchinson Cancer Research Center.)
"¢ Session: 625. Lymphoma: Pre-Clinical "“ Chemotherapy and Biologic Agents:
Poster II
"¢ Date: Sunday, December 8, 2019, 6:00 p.m. "“ 8:00 p.m. Eastern Standard Time
o CAR T cells treated with NKTR-255 demonstrate increased proliferation
and survival both in vitro and in vivo which may in part be due to increased
expression of bcl-2.
o Tumor bearing mice treated with NKTR-255 and CAR T cells have
decreased tumor burden and increased survival compared to mice treated
with CAR T cells alone.
o Tumor-bearing mice previously treated with NKTR-255 and CAR T cells
are able to reject tumor re-challenge supporting persistence of functional
CAR T cells.
Abstract 4398: “Restoring innate and adaptive immune repertoire in multiple
myeloma for therapeutic application,” Fernandez, R., et al. (This study was
conducted in collaboration with Dr. Nikhil C. Munshi at the Dana Farber/Harvard
Cancer Center SPORE in Multiple Myeloma.)
"¢ Session: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, Excluding
Therapy: Poster III
"¢ Date: Monday, December 9, 2019, 6:00 p.m. "“ 8:00 pm. Eastern Standard Time
o Multiple myeloma patients are known to experience impaired innate
immunity and a decline in function of NK cells along with lower expression
of activating receptors found on these cells.
o Treatment with NKTR-255 enhanced the number and function of both NK
and CD8+ effector memory T cell populations in peripheral blood from
healthy donors and MM patients in a dose dependent manner.
o NKTR-255 was also able to revert the inhibitory status of NK cells from
MM patients and showed synergy with daratumumab and elotuzumab to
significantly increase status of NK susceptibility of the MM cells.
o Findings suggest NKTR-255 delivers a significant impact on the activation
of effector cell function to efficiently target MM cells.
Details of the Trials in Progress poster presentation are as follows:
Abstract 4459: "A Phase 1, Open-Label, Multi-Center, Dose Escalation and Dose
Expansion Study of NKTR-255 As a Single Agent in Relapsed or Refractory
Hematologic Malignancies and in Combination with Daratumumab As a Salvage
Regimen for Multiple Myeloma," Shah, N., et al.
"¢ Session: 704. Immunotherapies: Poster III
"¢ Date: Monday, December 9, 2019; 6:00 p.m. "“ 8:00 p.m. Eastern Standard Time
About the Phase 1 Study of NKTR-255 (NCT04136756)
NKTR-255 is currently being evaluated in an open-label Phase 1, dose escalation and
dose expansion study in patients with select hematological malignancies (relapsed or
refractory NHL or MM). The dose escalation phase of the study will evaluate the safety
and tolerability of NKTR-255 as monotherapy in approximately 40 patients in order to
establish a recommended Phase 2 dose (RP2D) for NKTR-255. The dose expansion
phase of the study will enroll patients with MM or NHL (relapsed/refractory salvage) to
evaluate the NKTR-255 RP2D in combination with targeted antibodies, including anti-
CD38 monoclonal antibody, daratumumab in MM and anti-CD20 monoclonal antibody,
rituximab in NHL. These studies are designed to assess pharmacokinetic and
pharmacodynamic effects, anti-tumor activity and a range of biomarker assessments
associated with NK and memory T cell populations.
About NKTR-255
NKTR-255 is an IL-15 receptor agonist designed to activate the IL-15 pathway and
expand NK cells and promote the survival and expansion of memory CD8+ T cells
without inducing suppressive regulatory T cells. Through optimal engagement of the IL-
15Rα/IL-2Rβγ receptor complex, NKTR-255 enhances functional NK cell repopulation
and formation of long-term immunological memory, which may lead to sustained anti-
tumor immune response. NKTR-255 is uniquely designed to overcome the challenges
of recombinant IL-15 and other IL-15 agonists, which are rapidly cleared from the body
and have shown diminishing response to successive doses.
1 Designed using Nektar"™s
polymer conjugation technology to extend circulating half-life, NKTR-255 can be dosed
every 14 or 21 days.
About Nektar Therapeutics
Nektar Therapeutics is a research-based, development-stage biopharmaceutical
company whose mission is to discover and develop innovative medicines to address the
unmet medical needs of patients. Our R&D pipeline of new investigational medicines
includes treatments for cancer, autoimmune disease and chronic pain. We leverage
Nektar’s proprietary and proven chemistry platform in the discovery and design of our
new therapeutic candidates. Nektar is headquartered in San Francisco, California, with
additional operations in Huntsville, Alabama and Hyderabad, India. Further information
about the company and its drug development programs and capabilities may be found
online at http://www.nektar.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements which can be identified by
words such as: “promise,” “potential,” “design,” “enhance,” “may,” “will” and similar
references to future periods. Examples of forward-looking statements include, among
others, statements we make regarding the expected benefits of NKTR-255 (both alone
as a single agent as well as in combination with other agents, such as targeted
antibodies), the ability to obtain useful data from the Phase 1 clinical study of NKTR-
255, and the future clinical development plans for NKTR-255. Forward-looking
statements are neither historical facts nor assurances of future performance. Instead,
they are based only on our current beliefs, expectations and assumptions regarding the
future of our business, future plans and strategies, anticipated events and trends, and
other future conditions. Because forward-looking statements relate to the future, they
are subject to inherent uncertainties, risks and changes in circumstances that are
difficult to predict and many of which are outside of our control. Our actual results may
differ materially from those indicated in the forward-looking statements. Therefore, you
should not rely on any of these forward-looking statements. Important factors that could
cause our actual results to differ materially from those indicated in the forward-looking
statements include, among others: (i) NKTR-255 is in early-stage clinical development
and there are substantial risks that can unexpectedly occur for numerous reasons
including negative safety and efficacy findings in the Phase 1 clinical study
notwithstanding positive preclinical findings; (ii) clinical study outcomes, including the
Phase 1 clinical study outcome of NKTR-255, remain very unpredictable and it is
possible that a clinical study could fail due to efficacy, safety or other important clinical
findings; (iii) the timing of the commencement or end of clinical trials and the availability
of clinical data may be delayed or unsuccessful due to regulatory delays, slower than
anticipated patient enrollment, manufacturing challenges, changing standards of care,
evolving regulatory requirements, clinical trial design, clinical outcomes, and competitive
factors; (iv) scientific discovery of new therapeutics is an inherently uncertain process
and the future success of applying our technology platform to potential new drug
candidates (such as NKTR-255) is therefore highly uncertain and unpredictable; (v)
patents may not issue from our patent applications for NKTR-255, patents that have
issued may not be enforceable, or additional intellectual property licenses from third
parties may be required; and (vi) certain other important risks and uncertainties set forth
in Nektar’s Quarterly Report on Form 10-Q filed with the Securities and Exchange
Commission on November 7, 2019. Any forward-looking statement made by us in this
press release is based only on information currently available to us and speaks only as
of the date on which it is made. We undertake no obligation to update any forward-
looking statement, whether written or oral, that may be made from time to time, whether
as a result of new information, future developments or otherwise.
Contact:
For Investors:
Vivian Wu of Nektar Therapeutics
628-895-0661
For Media:
Jodi Sievers of Nektar Therapeutics
415-482-5593
Dan Budwick of 1AB
973-271-6085
dan@1abmedia.com
1. Blood 2018 Jun 7;131(23):2515-2527