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.

Blueprint Medicines announced this morning that the second part of its study on Ayvakit in non-advanced systemic mastocytosis (SM) — a rare disease in which a type of white blood cells known as mast cells builds up — met all endpoints, but the biopharma left key questions unanswered.

In 212 patients, with 141 in the treatment arm and 71 in the control arm, patients who got Ayvakit saw an average 15.6-point decrease in their symptom scores compared to a 9.2-point decrease in the placebo arm at 24 weeks. In an extension study, those on Ayvakit saw their symptom scores drop by 20.2 points by week 48.

GSK has landed a new first from UNICEF — the first-ever contract for malaria vaccines, worth up to $170 million for 18 million vaccine doses distributed over the next three years.

The vaccine, known as Mosquirix or RTS,S, won WHO’s backing last October after a controversial start, but UNICEF said these doses will potentially save thousands of lives every year.

“We hope this is just the beginning,” Etleva Kadilli, director of UNICEF’s supply division, said. “Continued innovation is needed to develop new and next-generation vaccines to increase available supply, and enable a healthier vaccine market. This is a giant step forward in our collective efforts to save children’s lives and reduce the burden of malaria as part of wider malaria prevention and control programmes.”