For decades, sci­en­tists scratched their heads about KRAS, the no­to­ri­ous can­cer-caus­ing pro­tein. Its smooth ter­rain long elud­ed ma­nip­u­la­tion, large­ly due to the ab­sence of a dis­tinct pock­et for a drug to latch on to. How­ev­er, the process of tri­al and er­ror fi­nal­ly yield­ed progress — trig­ger­ing a flock of com­pa­nies, in­clud­ing Am­gen, J&J, Mer­ck, and As­traZeneca, to en­gi­neer com­pounds de­signed to an­nex the oft’ mu­tat­ed onco­gene. And now, it looks like Ger­many’s Boehringer In­gel­heim has of­fi­cial­ly en­tered the fold.

The first KRAS pock­et es­tab­lished by Am­gen $AMGN for at­tack is G12C, al­though small­er ri­val Mi­rati $MRTX is at the large drug­mak­er’s heels. The KRAS G12C mu­ta­tion is found in rough­ly 14% of non-small cell lung can­cer (NSCLC) pa­tients and 5% of col­orec­tal can­cer pa­tients, who are large­ly pre­sent­ed with a poor prog­no­sis and tend to be re­sis­tant to stan­dard ther­a­pies.

On Tues­day, Ever­core ISI’s Umer Raf­fat point­ed out that Boehringer now has a clin­i­cal-stage KRAS in­hibitor in its ar­se­nal. And un­like Am­gen and Mi­rati, the Ger­man drug­mak­er’s ap­proach is a pan-KRAS in­hibitor that hits SOS1 as well as G12C. SOS1 is a pro­tein that turns KRAS from an “off” to “on” state.

Am­gen’s keen­ly watched AMGN510 made a splash at the AS­CO con­fer­ence this year af­ter a small, ear­ly study showed five out of 10 pa­tients suf­fer­ing from ad­vanced, drug-re­sis­tant NSCLC saw a par­tial re­sponse to the ex­per­i­men­tal treat­ment, in­clud­ing one who went on to achieve a com­plete re­sponse af­ter the da­ta cut­off point. Last month, those da­ta were up­dat­ed at the World Con­fer­ence on Lung Can­cer. Re­searchers tracked a 54% par­tial tu­mor re­sponse, and ob­served tu­mors shrink­ing in sev­en of 13 NSCLC pa­tients.

An­a­lysts have been in­tox­i­cat­ed with the po­ten­tial of the com­pound for this cat­e­go­ry of heav­i­ly treat­ed pa­tients with few op­tions at their dis­pos­al — and have al­ready fore­cast the drug will gen­er­ate bil­lions in peak sales, should it se­cure ap­proval.

But over the week­end at the ES­MO meet­ing in Barcelona, en­thu­si­asm for the drug out­side of lung can­cer damp­ened, af­ter Am­gen un­veiled da­ta from the tranche of col­orec­tal can­cer pa­tients. Re­searchers re­port­ed a sin­gle par­tial re­sponse among 12 col­orec­tal can­cer pa­tients.

Mean­while, Mi­rati’s Phase I/II da­ta em­a­nat­ing from its ex­per­i­men­tal drug, MRTX849, for ad­vanced sol­id tu­mors that har­bor KRAS G12C mu­ta­tions are ex­pect­ed in the fourth quar­ter. The lit­tle biotech has tied up with No­var­tis — and the two are look­ing at com­bin­ing the G12C drug with a ther­a­py that tar­gets SHP2, which func­tions as a key reg­u­la­tor of cell cy­cle con­trol.

Rev­o­lu­tion Med­i­cines has the same po­ten­tial com­bo in-house. Oth­er KRAS con­tenders in­clude Mod­er­na $MR­NA and Mer­ck’s $MRK mR­NA-5671; J&J’s $JNJ col­lab­o­ra­tion with Well­spring on ARS-3248, a G12C tar­get­ed small mol­e­cule; and AZD4785, li­censed by As­traZeneca $AZN from Io­n­is — al­though the com­pound has been dis­con­tin­ued af­ter a poor show­ing in clin­i­cal tri­als.

In Au­gust, Boehringer tied up with MD An­der­son in­ves­ti­ga­tors in Hous­ton to cre­ate a joint “vir­tu­al re­search and de­vel­op­ment cen­ter” look­ing at two pop­u­lar prospects: KRAS in­hi­bi­tion and a TRAILR2 ag­o­nis­tic an­ti­body for apop­to­sis.

As an onco­gene, KRAS has the po­ten­tial to ren­der nor­mal cells can­cer­ous. Akin to HRAS and NRAS, it be­longs to the RAS fam­i­ly of onco­genes and plays a key role in cell di­vi­sion, cell dif­fer­en­ti­a­tion, and apop­to­sis.

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.

Back in November, the Department of Health and Human Services took the rare step of filing a complaint against Gilead for infringing on government-owned patents related to the HIV drug Truvada (emtricitabine/tenofovir disoproxil fumarate) for pre-exposure prophylaxis (PrEP).

But on Thursday, Gilead filed its own retort, making clear that it does not believe it has infringed on the Centers for Disease Control and Prevention’s (CDC) Truvada patents because they are invalid.