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.

Biotech is one of the smartest, best educated industries on the planet. PhDs abound. We’ve had a long enough track record to see a new generation of savvy, experienced execs coming together to run startups.

And in these times, they are being tested as never before.

Biotech is going through quite a rough patch right now. For 2 years, practically anyone with a decent resume and some half-baked ideas on biotech could start a company and get it funded. The pandemic made it easy in many ways to pull off an IPO, with traditional road shows shut down in exchange for a series of quick Zoom meetings. Generalist investors flocked as the numbers raised soared into the stratosphere.

While calls to diversify clinical trials have grown louder in recent years — gaining support from federal agencies such as the FDA and NIH — progress has largely stalled, according to a new report from the National Academies of Sciences, Engineering and Medicine.

Swaths of patients in racial and ethnic minority groups, as well as LGBTQIA+, pregnant and older adult populations continue to be left out of clinical trials. While some advances have been made in the last 30 years — women now account for roughly half of clinical trial participants — growth in other areas remains stagnant, according to the report, which was mandated by Congress and sponsored by the NIH.

It seems that smallpox vaccination production is weighing on the mind of the US government. And manufacturer Bavarian Nordic is the latest company to benefit.

Just a few days after Emergent, a company that has made government contracts its lifeblood, acquired the exclusive rights to Tembexa from Chimerix, with a $225 million cash payment and an expected BARDA contract, the agency has offered a contract for smallpox vaccine production.

The House Energy and Commerce Committee on Wednesday offered a rare show of bipartisan support for a bill that would provide the FDA with user fees for the next five years.

The committee voted 55-0 to advance the quinquennial user fee bill to the full House floor, which if approved, will allow the FDA to use biopharma funds to hire new reviewers, and hit new marks as outlined in the user fee deals that the FDA and biopharma companies forged over the past several years.