Jon Wigginton, Cullinan Oncology CMO

Cul­li­nan On­col­o­gy launch­es new sub­sidiary fo­cused on col­la­gen-bind­ing cy­tokine treat­ment

Cul­li­nan On­col­o­gy op­er­ates as both a biotech and an in­vest­ment fund, hous­ing each of its as­sets in sub­sidiaries un­der one large um­brel­la. A lit­tle over a month af­ter its last launch, Cul­li­nan has an­nounced an­oth­er such project.

The Cam­bridge-based com­pa­ny in­tro­duced Cul­li­nan Am­ber on Wednes­day morn­ing, the ninth drug de­vel­op­ment en­ter­prise in its port­fo­lio, and has ob­tained an ex­clu­sive li­cense from MIT to uti­lize col­la­gen bind­ing tech­nol­o­gy. Thanks to this tech, Cul­li­nan Am­ber’s lead pro­gram will com­bine two an­ti­tu­mor cy­tokines, IL-12 and IL-2, with a col­la­gen-bind­ing do­main to pro­duce what CMO Jon Wig­gin­ton hopes are more lo­cal­ized can­cer treat­ments.

“When you in­ject this mol­e­cule in­to the tu­mor,” Wig­gin­ton said, “it me­di­ates sig­nif­i­cant an­ti­tu­mor ac­tiv­i­ty, and by virtue of its col­la­gen-bind­ing do­main, it binds the col­la­gen in the tu­mor and is re­tained there bet­ter.”

In­ter­leukins play a role in en­hanc­ing the body’s im­mune sys­tem, stim­u­lat­ing T and NK cell pop­u­la­tions to at­tack tu­mor sites. But like many can­cer im­munother­a­pies, this can lead to high tox­i­c­i­ty in healthy cells.

Cul­li­nan Am­ber’s plan is to de­vel­op a sin­gle mol­e­cule that con­tains both IL-12 and IL-2, with the MIT tech pro­vid­ing a way to keep the im­mune re­sponse at the tu­mor site. Pre­clin­i­cal an­i­mal test­ing has shown that by in­ject­ing the com­pound di­rect­ly in­to the tu­mor and bind­ing to the tu­mor col­la­gen, the cy­tokines stayed with­in the tu­mor en­vi­ron­ment. This tech was pi­o­neered by MIT pro­fes­sor K. Dane Wit­trup, who will be ad­vis­ing the Cul­li­nan Am­ber team.

Owen Hugh­es

“What we’ve been able to show is not on­ly do the an­i­mals gain weight over time, sim­i­lar to the con­trol group, but we es­sen­tial­ly evis­cer­ate their tu­mors,” CEO Owen Hugh­es said. “It’s re­al­ly the ad­vent of the col­la­gen-bind­ing do­main that al­lows us to cap­i­tal­ize on what is very po­tent an­ti­tu­mor ac­tiv­i­ty with these cy­tokines.”

Of course, col­la­gen is present through­out the hu­man body, and though ear­ly an­i­mal test­ing has en­cour­aged Cul­li­nan, the next chal­lenge is to en­sure such re­sults trans­late to hu­mans. This is the stage at which sev­er­al com­pa­nies pre­vi­ous­ly aban­doned their IL-12 and IL-2 projects, Wig­gin­ton said, be­cause of the tox­i­c­i­ty as­so­ci­at­ed with the cy­tokines.

If some of the IL-12 and IL-2 were to spread out­side the tu­mor en­vi­ron­ment in hu­mans, side ef­fects would be ev­i­dent al­most right away, Wig­gin­ton said. But thus far, the col­la­gen-bind­ing do­main has proven quite ef­fec­tive and some test­ing has even shown signs of elim­i­nat­ing dis­tant tu­mors.

“Peo­ple his­tor­i­cal­ly have in­ject­ed oth­er agents like IL-12 in­to tu­mors, but those ap­proach­es have been lim­it­ed by, in some cas­es, they haven’t shown the abil­i­ty to gen­er­ate sys­temic im­mu­ni­ty,” Wig­gin­ton said. “We think that the agent will solve sev­er­al his­tor­i­cal chal­lenges in the phase de­vel­op­ment of cy­tokines, and cre­ate the op­por­tu­ni­ty then to bring com­bi­na­tions to­geth­er with much more fa­vor­able risk ben­e­fit.”

Tar­get­ing those off-site tu­mors will be the next step for Cul­li­nan Am­ber as it moves in­to clin­i­cal stages. IND-en­abling stud­ies are ex­pect­ed to be­gin some­time be­fore the end of 2020.

Though lots of tests re­main, Wig­gin­ton hopes the com­pound can ul­ti­mate­ly be safe­ly used across a va­ri­ety of sol­id tu­mor can­cers.

“This is not a mol­e­cule that should nec­es­sar­i­ly be re­strict­ed to a spe­cif­ic tu­mor type,” Wig­gin­ton said. “We would start out with a Phase I tri­al with a mix of dif­fer­ent tu­mor pa­tients, guid­ed by what we see from that and any trans­la­tion­al stud­ies, and prob­a­bly pick a small num­ber of co­hort ex­pan­sions to be­gin to char­ac­ter­ize the an­ti­tu­mor ac­tiv­i­ties and see how the mol­e­cule is safe and well-tol­er­at­ed.”

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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Pfiz­er scoops up an an­tibi­ot­ic in rare M&A deal, bag­ging a vir­tu­al start­up op­er­at­ing on a shoe­string bud­get

Pfizer is stepping up with a rare antibiotics buyout deal today, grabbing Palo Alto, CA-based Arixa Pharmaceuticals in a bid to add a new oral version of avibactam, a beta lactamase inhibitor — or BLI — approved back in 2015 as part of the IV treatment Avycaz.

The Arixa acquisition follows some encouraging Phase I responses demonstrating that 60% to 80% of the oral drug is absorbed into the bloodstream. Only 7% of the IV version is absorbed orally, far below the 30% threshold Arixa has pointed to as a therapeutic threshold. The buyout gives Pfizer’s hospital group a line on a new oral combo with antibiotics like ceftibuten to go after drug-resistant cases of urinary tract infections and other ailments.

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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.

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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Adam Koppel and Jeffrey Schwartz, Bain

Bain ex­ecs Adam Kop­pel and Jef­frey Schwartz line up $125M for their first blank check deal as Wall Street con­tin­ues to em­brace biotech

Adam Koppel and Jeffrey Schwartz have jumped into the blank check game, raising $125 million for a stock listing in search of a company.

Their SPAC, BCLS Acquisition Corp, raised $125 million this week, with a line on $25 million more as it scouts for a biotech in search of money and a place on Wall Street.

The two principals at Bain Life Sciences have been on a romp since they set up the Bain operation 4 years ago. Their S-1 spells out a track record of 22 deals totaling $650 million for the life sciences group, which led to 9 IPOs.

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: 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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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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Covid-19 roundup: An mR­NA play­er gets a boost out of the lat­est round of an­i­mal da­ta; Phase­Bio pulls the plug on treat­ment tri­al

The big tell for CureVac $CVAC is coming up with a looming early-stage readout on their mRNA Covid-19 vaccine in the clinic. But for now they’ll make do with an upbeat assessment on the preclinical animal data they used to get into the clinic.

Researchers for the German biotech say they got the high antibody titers and T cell activation they were looking for, lining up a hamster challenge to demonstrate — in a simple model — that the vaccine could protect the furry creatures. Like the other mRNA vaccines, the drug sends instructions to spur cells to decorate themselves with the distinctive spike on the virus to elicit an immune response.