Back in 2015 NEA Ven­tures, SR One and No­vo Hold­ings pulled to­geth­er $11 mil­lion to kick­start the lat­est ven­ture to come out of Dario Cam­pana’s lab — which has al­so birthed Unum and Me­diS­ix — fo­cused on nat­ur­al killer (NK) cells. Four stealthy years lat­er, Nkar­ta is poised for the clin­ic with a $114 mil­lion Se­ries B to fu­el the big leap.

While the cur­rent buzz on cell ther­a­pies for can­cer has gen­er­al­ly cen­tered around some vari­a­tion of T cells from the ap­proved CAR-T to TCR, Nkar­ta be­lieves NK cells of­fer ad­van­tages that T cells lack. Since they are part of the in­nate im­mune sys­tem, NK cells can iden­ti­fy and hit a broad­er range of tar­gets pre­sent­ed on tu­mor cells.

“Rather than re­act to anti­gens that are be­ing pre­sent­ed by for­eign in­vaders of the sys­tem, NK cells are there to make sure your own cells are be­hav­ing the way that they should,” said Nadir Mah­mood, SVP of cor­po­rate de­vel­op­ment.

Nadir Mah­mood

Click on the im­age to see the full-sized ver­sion

But they al­so make up a small por­tion of the im­mune cell pop­u­la­tion and their po­ten­cy could wane quick­ly. Cam­pana’s break­through is de­vis­ing ways to grow NK cells from healthy donors quick­ly by co-cul­tur­ing them with co-stim­u­la­to­ry cell lines, while en­gi­neer­ing them to ex­press a mem­brane bound form of IL-15, en­hanc­ing their per­sis­tence, Mah­mood added.

Build­ing on those foun­da­tion­al tech­nolo­gies, the Nkar­ta team has ze­roed in on NKX101, which they call fourth-gen­er­a­tion CAR-NK cells. Un­like the chimeric anti­gen re­cep­tor pro­grammed in­to T cells — which typ­i­cal­ly cor­re­sponds to one anti­gen — their CAR is de­signed to hit a tar­get called NKG2D as­so­ci­at­ed with up to eight lig­ands that can be found on tu­mor cells.

“The CAR for­mat makes it a more po­tent sig­naler of the cy­to­tox­ic ac­tiv­i­ty in the NK cell,” Mah­mood said of their ”su­per­charged” prod­uct.

Dario Cam­pana

It promis­es to be much more pow­er­ful than the NK en­gager ap­proach tak­en by Drag­on­fly and Af­fimed, which has gen­er­at­ed con­sid­er­able in­ter­est­ed from big play­ers like Mer­ck, Cel­gene and Genen­tech. Giv­en that NK cells from tu­mor pa­tients are im­paired and ex­haust­ed, Mah­mood said, an en­gager is es­sen­tial­ly re­cruit­ing a weak­er at­tack­er than what Nkar­ta of­fers.

With an IND planned for lat­er this year, Nkar­ta will fo­cus on re­lapsed, re­frac­to­ry cas­es of acute myeloid leukemia as their first hema­to­log­ic in­di­ca­tion. As for sol­id tu­mors, they will test a lo­cal de­liv­ery aimed at tam­ing liv­er as­so­ci­at­ed metas­tases.

A sec­ond CAR-NK pro­gram tar­get­ing CD19 in B-cell ma­lig­nan­cies is be­ing shep­herd­ed through pre­clin­i­cal stud­ies.

The tri­als will al­so rep­re­sent a test for Nkar­ta’s man­u­fac­tur­ing abil­i­ties. On top of clin­i­cal moves, in­vestors in the fi­nanc­ing — with Sam­sara Bio­Cap­i­tal lead­ing Am­gen Ven­tures, Deer­field Man­age­ment, Life Sci­ence Part­ners, Lo­gos Cap­i­tal and RA Cap­i­tal Man­age­ment — are al­so bankrolling a clin­i­cal GMP fa­cil­i­ty just a lev­el above Nkar­ta’s South San Fran­cis­co of­fices.

It’s not ex­pen­sive — Nkar­ta is pen­cilling in “sin­gle-dig­it mil­lions” in the bud­get — but mov­ing man­u­fac­tur­ing op­er­a­tions from aca­d­e­m­ic fa­cil­i­ties to their own would be cru­cial for main­tain­ing con­trol to the know-how, CEO Paul Hast­ings said.

“As you know in cell ther­a­py, the process is the prod­uct,” he said.

Matt Plun­kett

And it’s a process they are clear­ly proud of. CFO Matt Plun­kett added that each man­u­fac­tur­ing run yields hun­dreds if not low thou­sands of dos­es, low­er­ing the cost of goods to “two or­ders of mag­ni­tude be­low that of” Kym­ri­ah and Yescar­ta.

Nkar­ta is un­veil­ing its plans just as Fate Ther­a­peu­tics, a fel­low NK cell ther­a­py play­er that Hast­ings “has a lot of re­spect for,” an­nounced their first IND has been cleared. In­stead of healthy donors, Fate de­rives its NK cells from in­duced pluripo­tent stem cells (iP­SC).

The bat­tle for sec­ond-gen NK cell ther­a­peu­tics is just get­ting start­ed.

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Six years after Kura Oncology snagged a farnesyl transferase inhibitor from J&J and leapt straight into clinical development, one of the biotech’s founders is leaving to start a new chapter in his career.

CMO and development chief Antonio Gualberto is exiting the company, and Kura — led by longtime biotech entrepreneur Troy Wilson — is on the hunt for a replacement. Wilson credited the CMO for some key biomarker work, including the discovery of the CXCL12 pathway as a target of their lead drug tipifarnib. Those biomarkers are being relied on to define the patient population most likely to benefit from the drug.

After winning the hearts of the expert panel convened by the FDA despite a bleak in-house review and a checkered development history, Robert Bazemore has steered Epizyme to its first-ever OK for a rare cancer drug.

The approval in epithelioid sarcoma sets tazemetostat, now Tazverik, up nicely for a quick expansion to follicular lymphoma — a much bigger indication for which the biotech has just submitted an NDA.

The FDA on Thursday finalized two guidances providing recommendations to drugmakers on evaluating potential drug-drug interactions (DDIs) for new drugs through clinical and in vitro testing.

“Together, the two final guidances describe a systematic risk-based approach to evaluation and communication of DDIs,” the FDA writes.

The two guidances finalize draft versions released in 2017 and have been revised to clarify their scope, provide additional considerations for conducting prospective studies and to explain “when DDI studies are needed for drugs identified as transporter substrates from in vitro studies.” Both guidances have been renamed from their draft versions to reflect an emphasis on investigating the cytochrome P450 (CYP) enzyme and transporter-mediated drug interactions.