Less than stel­lar Phase I re­sults have trig­gered a pipeline cleanup at Sy­ros Phar­ma, where one of its two lead drugs — a CDK7 in­hibitor ad­min­is­tered in­tra­venous­ly — is get­ting swapped out with an oral ver­sion.

The biotech said it main­tains its be­lief in the CDK7 path­way for can­cer, but thinks pri­or­i­tiz­ing SY-5609, which ap­pears more se­lec­tive and po­tent in pre­clin­i­cal mod­els, is a wis­er choice than hold­ing on­to an IV drug that didn’t quite em­body the op­ti­mal bal­ance be­tween ef­fi­ca­cy and tol­er­a­bil­i­ty. A hu­man tri­al for SY-5609 is planned for ear­ly next year.

Sy­ros had po­si­tioned SY-1365 in a num­ber of sol­id tu­mors marked by spe­cif­ic ge­net­ic mu­ta­tions, in­clud­ing ovar­i­an and breast can­cers. Hav­ing treat­ed 68 pa­tients in an ex­pan­sion por­tion of the tri­al with both sin­gle-agent and com­bi­na­tion ther­a­pies — tar­get­ing some pa­tients who are re­sis­tant to CDK4/6 in­hibitors — in­ves­ti­ga­tors con­clud­ed they would need more fre­quent dos­ing to sus­tain the lev­el of CDK7 they need.

No­tably, on­ly 24 pa­tients were evalu­able at the da­ta cut­off, and none had bet­ter re­sponse than sta­ble dis­ease. Of those treat­ed with sin­gle-agent SY-1365, 42% had sta­ble dis­ease as de­fined by RE­CIST cri­te­ria, and the per­cent­age was 64% in the com­bo group (who were al­so giv­en ful­ves­trant or car­bo­platin).

Nan­cy Si­mon­ian Sy­ros

“We have gained im­por­tant in­sights from our work on SY-1365 that have in­formed our de­vel­op­ment strat­e­gy for SY-5609, in­clud­ing fo­cus­ing on pa­tient pop­u­la­tions most like­ly to re­spond to a CDK7 in­hibitor,” CEO Nan­cy Si­mon­ian said in a state­ment. “We are pri­or­i­tiz­ing SY-5609 be­cause we be­lieve it has best-in-class po­ten­tial and that it pro­vides the great­est op­por­tu­ni­ty to re­al­ize the promise of se­lec­tive CDK7 in­hi­bi­tion for pa­tients.”

In­vestors, though, saw the glass half emp­ty. Shares $SYRS are down 33.32% to $6.74.

This is not the first time Sy­ros’ lead drugs have dis­ap­point­ed. SY-1425, their RARα ag­o­nist de­ployed against acute myeloid leukemia, flopped in a Phase II two years ago. Sy­ros is con­duct­ing an­oth­er tri­al pair­ing the drug with azac­i­ti­dine, the stan­dard of care, that they say is turn­ing up high­er re­sponse rates. They will need some sol­id, hard da­ta to win skep­tics back.

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

The FDA adcomm has advanced to the free-for-all question stage of the hearing and, as they did for Moderna and Pfizer, committee members are raising questions about the lingering issues surrounding the vaccine.

In J&J’s case, one of those unknowns is a group of participants who appeared to respond worse to the vaccine: those over 60 with comorbidities. In that group, the vaccine was only 42% effective at stopping disease starting 28 days after vaccination.

Genentech has committed $53 million to back a 10-year quest aimed at going back to the drawing board to use new technology and fresh scientific insights to generate a pipeline of drugs for neurological diseases.

Roche’s big South San Francisco hub will mix it up with the scientists drawn together for the Weill Neurohub — formed in 2019 as a joint research partnership involving UCSF, Berkeley and the University of Washington — in an exploration of the field to develop new therapies for some of the toughest diseases in drug R&D: Alzheimer’s, Parkinson’s, Huntington’s, ALS and autism.

On the hunt for a novel competitor to Sanofi and Regeneron’s Dupixent in severe asthma, Amgen and AstraZeneca posted “exciting” results from their next-gen antibody late last year. Now, the partners are showing their hands, and the results look good enough for approval.

Amgen and AstraZeneca’s tezepelumab plus standard of care cut the rate of severe asthma attacks by 56% at the one-year mark compared with SOC alone, according to full data from the Phase III NAVIGATOR study presented Friday at the virtual American Academy of Allergy, Asthma & Immunology meeting. And those significant results were consistent regardless of patients’ baseline eosinophil counts.