San Francisco, CA (Press Release) – Nektar Thera­peutics (NASDAQ: NKTR) today announced the initiation of a first-in-human, Phase 1 clin­i­cal study eval­u­ating NKTR-255, an interleukin-15 (IL-15) re­cep­tor agonist, as mono­therapy for patients with re­lapsed or re­frac­tory non-Hodgkin lym­phoma (NHL) or multiple myeloma (MM). The study will also combine NKTR-255 with multiple targeted anti­bodies, that function through an anti­body-dependent cell-mediated cyto­tox­icity (ADCC) mech­a­nism, to eval­u­ate the safety and efficacy in adults with re­lapsed or re­frac­tory MM. NKTR-255 is designed to activate the IL-15 path­way and ex­pand functionally superior natural killer (NK) cells and promote the survival and ex­pan­sion of memory CD8+ T cells without inducing sup­pres­sive regu­la­tory T cells.

"We are excited to launch the first-in-human clin­i­cal study of NKTR-255, which has shown promising and sub­stan­tial anti-tumor activity in our pre­clin­i­cal studies," said Wei Lin, M.D., Senior Vice Pres­i­dent and Head of Development at Nektar Thera­peutics. "By in­creas­ing the number and activity of NK cells, NKTR-255 has the poten­tial to en­hance the host's tumor-fighting response, both as a single agent and in com­bi­na­tion with tumor-targeting anti­bodies, in­clud­ing dara­tu­mu­mab and ritux­i­mab­."

One of the big chal­lenges in treating cancer patients with targeted mono­clonal anti­bodies is that the cancer patients have a deficiency in key effector cells like NK cells that are needed to work with the mono­clonal anti­bodies.^1,2 In nonclinical studies, NKTR-255 exhibited anti-tumor activity and sub­stan­tially en­hanced in vivo pro­lif­er­a­tion and activation of NK cells to provide sustained cytotoxic function.³ In a pre­clin­i­cal lym­phoma model where single agent dara­tu­mu­mab was ineffective, NKTR-255 treat­ment, in com­bi­na­tion with dara­tu­mu­mab, in­creased NK cell numbers and activity in bone marrow tissue and en­hanced ADCC-mediated tumor cell clear­ance in the bone marrow compartment.⁴

NHL is one of the most common cancers in the United States, accounting for about 4% of all cancers. The American Cancer Society esti­mates that in 2019, approx­i­mately 74,200 people will be diag­nosed with NHL in the U.S. and about 19,970 will die from this cancer. MM is a rel­a­tive­ly uncommon cancer in the U.S., with a lifetime risk of getting MM of 1 in 132 (0.76%). The American Cancer Society esti­mates that in 2019, approx­i­mately 32,110 people will be diag­nosed with MM and about 12,960 will die from this dis­ease.

About the NKTR-255 Phase 1 Study

The NKTR-255 Phase 1 study is an open-label, 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 in two separate cohorts: the first cohort will enroll patients with MM or NHL (relapsed salvage) to eval­u­ate the NKTR-255 RP2D as a mono­therapy and the second cohort 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. The study will also eval­u­ate phar­ma­co­ki­netic and pharmacodynamic effects, anti-tumor activity and bio­marker assess­ments.

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 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, which is rapidly cleared from the body and must be admin­istered frequently and in high doses, limiting its utility due to toxicity and convenience of use.

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: "promising," "poten­tial," "design," "provide," "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 multiple 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 August 9, 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.

Reerences

1. Messaoudene M., et al., (2017) Patient's Natural Killer Cells in the Era of Targeted Therapies: Role for Tumor Killers. Front. Immunol. 8:683.
2. Farnault, L., et al., Hematological Malignancies Escape from NK Cell Innate Immune Surveillance: Mechanisms and Thera­peutic Implications. Clinical and Developmental Immunology Volume 2012, Article ID 421702, 8 pages
3. Journal for ImmunoTherapy of Cancer 2017 5(Suppl 2):87; P332.
4. Miyazaki T., et al., NKTR-255, a polymer-conjugated IL-15 en­hances anti-tumor NK cell responses and synergizes with mono­clonal anti­bodies to provide long-term survival in human lym­phoma model. In: Proceedings of the Annual Meeting of the AACR; 2019. Abstract 3265.

Source: Nektar Thera­peutics.