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.”

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 105,400+ biopharma pros reading Endpoints daily — and it's free.

Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

Pfiz­er, Bris­tol My­er­s' Eliquis flops in post-heart surgery pa­tients, spurring an 'un­ex­plained sig­nal' in cer­tain deaths

Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.

Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 105,400+ biopharma pros reading Endpoints daily — and it's free.

Abbie Celniker (L) and Rob Sims (Flare)

A Third Rock-backed play­er charts a new course against tran­scrip­tion fac­tors. Do 'switch sites' hold the mag­ic sauce?

Long known for their role in guiding gene expression but considered “undruggable,” DNA binding transcription factors have long been a Holy Grail for drug developers. Now, a new startup from Third Rock Ventures thinks it could have the juice to get after transcription factors once and for all — and it all started with a “flare” of inspiration from an article out of an Oxford lab.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 105,400+ biopharma pros reading Endpoints daily — and it's free.