Nektar Therapeutics (NKTR) is conducting a trial that will test NKTR-255 in patients with relapsed-refractory non-Hodgkin lymphoma (NHL) or multiple myeloma (MM), explains biotech specialist John McCamant, editor of The Medical Technology Stock Letter.

The NKTR-255 Phase I 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 II 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.

NKTR-255 is an IL-15 receptor agonist designed to engage the IL-15 pathway to stimulate and expand natural killer (NK) cells and promote the survival and expansion of central memory CD8+ T cells without inducing suppressive regulatory T cells. 

Il-15 is very similar to IL-2, the target for bempeg, in that it has a very short half-life in the body limiting its therapeutic effectiveness. IL-15 is a cytokine that primarily stimulates the proliferation and cytotoxic functions of CD8 T cells and NK cells leading to enhanced anti-tumor responses.

While initially showing promise as a cancer therapeutic, the efficacy of IL-15 was limited by its short in vivo half-life. More recently, various approaches have been developed to improve the in vivo half-life and efficacy.

NKTR-255 is a very novel I/O molecule that we believe is completely ignored by investors as it sits in the negative shadow of bempeg.  We still believe bempeg data will begin to demonstrate the difference between the good and the bad manufactured lots and eventually lead to re-appreciate the potential of both ‘214 and ‘255.

Additionally, ‘181 has also fallen out of favor with the current FDA delay. We believe that NKTR’s stock is significantly undervalued due to it being a major target for October tax loss selling and that any good news could turn the stock around on a dime.

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