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.”

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

The End­points 11: They've got mad mon­ey and huge am­bi­tions. It's time to go big or go home

These days, selecting a group of private biotechs for the Endpoints 11 spotlight begins with a sprint to get ahead of IPOs and the M&A teams at Big Pharma. I’ve had a couple of faceplants earlier this year, watching some of the biotechs on my short list choose a quick leap onto Nasdaq or into the arms of a buyer.

Vividion, you would have been a great pick for the Endpoints 11. I’m sorry I missed you.

Endpoints Premium

Premium subscription required

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

Dave Lennon, former president of Novartis Gene Therapies

So what hap­pened with No­var­tis Gene Ther­a­pies? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

Endpoints Premium

Premium subscription required

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

Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

Jean Bennett (Brent N. Clarke/Invision/AP Images)

Lux­tur­na in­ven­tor Jean Ben­nett starts a new gene ther­a­py com­pa­ny to tack­le rare dis­eases left be­hind by phar­ma, VCs

A few years ago Jean Bennett found herself in a surprising place for a woman who invented the first gene therapy ever approved in the United States: No one, it seemed, wanted her work.

Bennett, who designed and co-developed Luxturna, approved in 2018 for a rare form of blindness, had kept building new gene therapies for eye diseases at her University of Pennsylvania lab. But although the results in animals looked promising, pharma companies and investors kept turning down the pedigreed ophthalmology professor.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 118,000+ biopharma pros reading Endpoints daily — and it's free.

FDA au­tho­rizes Pfiz­er's vac­cine boost­er for se­niors, those at high risk for se­vere Covid-19

The Biden administration’s goal of kicking off its booster shot drive for the entire US population this week is not quite going as planned.

First, Pfizer applied for approval of a supplemental application for the booster shots, but since last Friday’s adcomm reviewing them, the plan has devolved into an EUA, which the FDA issued late Thursday evening.

The population that is now eligible for the booster, six months after receiving the first pair of Pfizer-BioNTech vaccines, also narrowed from what Pfizer applied for (everyone who’s eligible for the initial Pfizer shots) to just those who are 65 or older, or at high-risk of a Covid infection, including health care workers and others with occupational hazards.

Stéphane Bancel, AP Images

Fi­nal analy­sis of US-fund­ed Mod­er­na Covid vac­cine tri­al shows 98% ef­fi­ca­cy against se­vere dis­ease

A final look at the results of the placebo-controlled Moderna trial in the New England Journal of Medicine, published Thursday afternoon, shows how the vaccine continues to prevent Covid-19 and severe cases after more than five months following the second shot.

Of the more than 30,000 enrolled in the trial that ultimately led to the vaccine’s EUA, only two people in the vaccine group got a severe form of the disease, compared to 106 in the placebo group — leading to an efficacy of 98%.

Emma Walmsley, GlaxoSmithKline CEO (Credit: Fang Zhe/Xinhua/Alamy Live News)

The fire un­der Glax­o­SmithK­line's Em­ma Walm­s­ley grows as an­oth­er well-known ac­tivist in­vestor grabs its pitch­fork — re­port

Bluebell Capital Partners, a proxy brawler fresh off a campaign to oust global food giant Danone’s CEO and most of its board of directors, has bought a stake in UK drugmaker GlaxoSmithKline with its eyes trained directly on Emma Walmsley, the Financial Times reported Wednesday.

The London-based hedge fund joins another notorious activist firm in Paul Singer’s Elliott Management, which earlier this year called for a shakeup in leadership at GSK to handle what the company described as a wealth of riches across the drug giant’s portfolio hindered by limited vision from top staff.

FDA+ roundup: Bs­U­FA III ready for show­time, court tells FDA to re-work com­pound­ing plan, new guid­ance up­dates and more

The FDA has now spelled out what exactly will be included in the third iteration of Biosimilar User Fee Act (BsUFA) from 2023 through 2027, which similarly to the prescription drug deal, sets fees that industry has to pay for submitting applications, in exchange for firm timelines that the agency must meet.

This latest deal includes several sweeteners for the biosimilar industry, which has yet to make great strides in the US market, with shorter review timelines for safety labeling updates and updates to add or remove an indication that does not contain efficacy data.

Endpoints Premium

Premium subscription required

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