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.

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

The Drugs for Neglected Diseases initiative (DNDi) and Sanofi today said that their potential sleeping sickness treatment saw success rates of up to 95% from a Phase II/III study investigating the safety and efficacy of single-dose acoziborole.

The potentially transformative treatment for sleeping sickness would mainly be targeted at African countries, according to data published today in The Lancet Infectious Diseases medical journal. The clinical trial was led by DNDi and its partners in the Democratic Republic of the Congo (DRC) and Guinea, with the authors noting: