Sy­ros push­es for a turn­around with new PhII AML re­sults, but in­vestors are unim­pressed

CEO Nan­cy Si­mon­ian

Two years af­ter weak Phase II re­sults cut their stock price in half, Sy­ros Phar­ma­ceu­ti­cals (SYRS) is back with re­sults from an on­go­ing Phase II tri­al try­ing their SY-1425 “su­per-en­hancer” ther­a­py in com­bi­na­tion with chemother­a­py on acute myeloid leukemia (AML) pa­tients. 

It’s ear­ly-stage and the num­bers are small, but of the 13 evalu­able pa­tients who test­ed pos­i­tive for the RARA path­way bio­mark­er Sy­ros’ ther­a­py tar­gets, re­searchers say that 8 had a com­plete re­sponse. That com­pared with 8 com­plete re­spons­es out of 22 pa­tients who didn’t have the gene. The longest CR was 344 days, com­pared with 168 for RARA neg­a­tive pa­tients, al­though Sy­ros not­ed the study is still on­go­ing.

“We show how when we se­lect the pa­tients who have po­ten­tial for a re­sponse, we have a high re­sponse rate,” Sy­ros CMO David Roth told End­points News. “And we show how these re­spons­es oc­cur rel­a­tive­ly quick­ly.”

Daniel J. DeAn­ge­lo, an on­col­o­gy ex­pert at the Dana-Far­ber In­sti­tute who is not af­fil­i­at­ed with Sy­ros, said the pa­tient pop­u­la­tion was small and the da­ta pre­lim­i­nary but that the re­sults were nev­er­the­less promis­ing for a sub­group of pa­tients. He not­ed the da­ta showed the drug on­ly worked on one of two bio­mark­ers Sy­ros had screened for, but that in pa­tients with RARA the re­sponse rate was around 70%.

“That’s about twice the re­sponse you would nor­mal­ly ex­pect” from chemother­a­py alone, DeAn­ge­lo told End­points.  “We don’t have any pro­gres­sion-free, sur­vival da­ta, and it’s a small num­ber [of pa­tients] – we’d want to con­firm it and all that – but looks re­al­ly in­ter­est­ing for that group of pa­tients.”

In­vestors, though, don’t ap­pear en­thused. Sy­ros’ stock dropped 4% to­day, con­tin­u­ing a fall of near­ly $5 per share since Oc­to­ber 17, when the biotech an­nounced it was shelv­ing a lead CDK7 in­hibitor in fa­vor of an oral ver­sion.

The 2017 tri­al test­ed SY-1425 as a sin­gle agent and found one com­plete or par­tial re­sponse out of 48 evalu­able pa­tients. In­vestors re­spond­ed with a sell­off that cut Sy­ros’s stock by over 50%. The com­pa­ny said at the time and has main­tained since that the “clin­i­cal ac­tiv­i­ty” in pa­tients val­i­dat­ed their ap­proach and point­ed to­ward com­bi­na­tion ther­a­pies as a log­i­cal next step.

Charles Baum, Mirati CEO

Mi­rati plots a march to the FDA for its KRAS G12C drug, breath­ing down Am­gen’s neck with bet­ter da­ta

Mirati Therapeutics $MRTX took another closely-watched step toward a now clearly defined goal to file for an approval for its KRAS G12C cancer drug adagrasib (MRTX849), scoring a higher response rate than the last readout from the class-leading rival at Amgen but still leaving open a raft of important questions about its future.

Following a snapshot of the first handful of responses, where the drug scored a tumor response in 3 of 5 patients with non-small cell lung cancer, the response rate has now slid to 45% among a pooled group of 51 early-stage and Phase II patients, 43% — 6 of 14 — when looking solely at the Phase I/Ib. Those 14 patients had a median treatment duration of 8.2 months, with half still on therapy and 5 of 6 responders still in response.

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In his­toric Covid-19 ad­comm, vac­cine ex­perts de­bate a sea of ques­tions — but of­fer no clear an­swers

The most widely anticipated and perhaps most widely watched meeting in the FDA’s 113-year history ended late Thursday night with a score of questions and very few answers.

For nearly 9 hours, 18 different outside experts listened to public health agencies and foundations present how the United States’ Covid-19 vaccine program developed through October, and they debated where it should go from there: Were companies testing the right metrics in their massive trials? How long should they track patients before declaring a vaccine safe or effective? Should a vaccine, once authorized, be given to the volunteers in the placebo arm of a trial?

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Michel Vounatsos, Biogen CEO (via YouTube)

Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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Biond­Vax stock im­plodes af­ter a big PhI­II gam­ble for its uni­ver­sal flu vac­cine fails

After flying high on Wall Street for the last few months of a pandemic, BiondVax’s stock and dreams of getting approval for its universal flu vaccine hit the windshield.

The Jerusalem-based biotech announced on Friday that its only clinical candidate, M-001, failed both primary and secondary endpoints in a Phase III study. There was no statistically significant difference in reduction of flu illness and severity between the vaccine and placebo groups, according to the company. The vaccine did prove safe, if ineffective, BiondVax said.

A top drug pro­gram at Bay­er clears a high bar for CKD — open­ing the door to an FDA pitch

Over the past 4 years, Bayer has been steering a major trial through a pivotal program to see if their drug finerenone could slow down the pace of chronic kidney disease in patients suffering from both CKD as well as Type 2 diabetes.

Today, their team jumped on a virtual meeting hosted by the American Society of Nephrology to offer a solid set of pivotal data to demonstrate that the drug can delay dialysis or a kidney replacement as well as cardio disease, while also adding some worrying signs of hyperkalemia among the patients taking the drug. And they’re hustling it straight to regulators in search of an approval for kidney disease and cardio patients — one of the toughest challenges in the book, as demonstrated by repeated past failures.

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Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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CRISPR Ther­a­peu­tics gets a snap­shot of off-the-shelf CAR-T suc­cess in B-cell ma­lig­nan­cies — marred by the death of a pa­tient

Just days after scientific founder Emmanuelle Charpentier shared the Nobel prize for her work on CRISPR/Cas9, CRISPR Therapeutics $CRSP is showing off a snapshot of success in their early-stage study for an off-the-shelf CAR-T approach to CD19+ B cell malignancies — a snapshot marred by the death of a patient who had been given a high dose of the treatment.

Using their gene editing tech, researchers for CRISPR engineered cells from healthy donors into an attack vehicle aimed at cancer, something that has been achieved with great success using patients’ own cells — the autologous approach. But autologous CAR-T is hampered by the more complex vein-to-vein requirement that delays treatment, and now CRISPR Therapeutics along with other players like Allogene are determined to replace the pioneers with CAR-T 2.0.

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Pascal Soriot, AstraZeneca CEO (Zach Gibson/Bloomberg via Getty Images)

UP­DAT­ED: FDA gives As­traZeneca the thumbs-up to restart PhI­II Covid-19 vac­cine tri­als, and J&J is prepar­ing to re­sume its study

Several countries had restarted their portions of AstraZeneca’s global Phase III Covid-19 vaccine trial after the study was paused worldwide in early September, but the US notably stayed on the sidelines — until now. Friday afternoon the pharma giant announced the all clear from US regulators. And on top of that, J&J announced Friday evening that it’s preparing to resume its own Phase III vaccine trial.

Ul­tragenyx in­jects $40M to grab Solid's mi­crody­s­trophin trans­gene — while side­step­ping the AAV9 vec­tor that stirred up safe­ty fears

Since before Ilan Ganot started Solid Bio to develop a gene therapy for kids like his son, who has Duchenne muscular dystrophy, Ultragenyx CEO Emil Kakkis has been watching and advising the former investment banker as he navigated the deep waters of drug development.

Just as Solid is getting back up on its feet after a yearlong clinical hold, Kakkis has decided to jump in for a formal alliance.

With a $40 million upfront, Ultragenyx is grabbing 14.45% of Solid’s shares $SLDB and the rights to its microdystrophin construct for use in combination with AAV8 vectors. Solid’s lead program, which utilizes AAV9, remains unaffected. The company also retains rights to other applications of its transgene.