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.”

Jan Hatzius (Photographer: Christopher Goodney/Bloomberg via Getty Images)

When will it end? Gold­man econ­o­mist gives late-stage vac­cines a good shot at tar­get­ing 'large shares' of the US by mid-2021 — but the down­side is daunt­ing

It took decades for hepatitis B research to deliver a slate of late-stage candidates capable of reining the disease in.

With Covid-19, the same timeline has devoured all of 5 months. And the outcome will influence the lives of billions of people and a multitrillion-dollar world economy.

Count the economists at Goldman Sachs as optimistic that at least one of these leading vaccines will stay on this furiously accelerated pace and get over the regulatory goal line before the end of this year, with a shot at several more near-term OKs. That in turn should lead to the production of billions of doses of vaccines that can create herd immunity in the US by the middle of next year, with Europe following a few months later.

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Ver­sant de­buts Ridge­line's start­up #4, armed with $30M and al­ter­na­tive TCR cell ther­a­pies for sol­id tu­mors

For all the iterations and advances in TCR therapies for cancer, any experimental treatments involving T cell receptors share one trait: By definition, they only recognize antigens presented as peptides on the major histocompatibility complex (MHC) on cells.

Versant reckons it’s time to expand the arsenal. With $30 million in initial funding, its Ridgeline Discovery Engine in Switzerland has been working on a non-peptidic approach that it says has tumor-agnostic potential, especially in solid tumors. They’ve named it Matterhorn, after a Swiss mountain as they did with the three other companies that have emerged from the Basel-based incubator.

UP­DAT­ED: No­vavax her­alds the lat­est pos­i­tive snap­shot of ear­ly-stage Covid-19 vac­cine — so why did its stock briefly crater?

High-flying Novavax $NVAX became the latest of the Covid-19 vaccine players to stake out a positive set of biomarker data from its early-stage look at its vaccine in humans.

Their adjuvanted Covid-19 vaccine was “well-tolerated and elicited robust antibody responses numerically superior to that seen in human convalescent sera,” the company noted. According to the biotech:

All subjects developed anti-spike IgG antibodies after a single dose of vaccine, many of them also developing wild-type virus neutralizing antibody responses, and after Dose 2, 100% of participants developed wild-type virus neutralizing antibody responses. Both anti-spike IgG and viral neutralization responses compared favorably to responses from patients with clinically significant COVID‑19 disease. Importantly, the IgG antibody response was highly correlated with neutralization titers, demonstrating that a significant proportion of antibodies were functional.

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Covid-19 roundup: BAR­DA qui­et­ly pulls plug on IL-6 drugs; BioN­Tech and Fo­s­un be­gin mR­NA tri­al

IL-6 inhibitors showed some early promise in potentially treating Covid-19 patients, but recent trial flops have dashed hopes. Now it appears BARDA has officially pulled the plug.

The HHS office’s website has quietly updated to reflect that it is “no longer supporting product development” for Covid-19 in both Actemra (tocilizumab) and Kevzara (sarilumab), dealing a blow to the Roche and Regeneron/Sanofi drugs. This all but assures that IL-6 drugs repurposed to treat Covid-19 are essentially dead in the water.

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J&J gets a fresh OK for es­ke­t­a­mine, but is it re­al­ly the game-chang­er for de­pres­sion Trump keeps tweet­ing about?

Backed by an enthusiastic set of tweets from President Trump and a landmark OK for depression, J&J scooped up a new approval from the FDA for Spravato today. But this latest advance will likely bring fresh scrutiny to a drug that’s spurred some serious questions about the data, as well as the price.

First, the approval.

Regulators stamped their OK on the use of Spravato — developed as esketamine, a nasal spray version of the party drug Special K or ketamine — for patients suffering from major depressive disorder with acute suicidal ideation or behavior.

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CF Foun­da­tion, Long­wood team on new in­cu­ba­tor for com­pa­nies with cut­ting-edge CF treat­ments

Nine months after launching a $500 million hunt for a cure for cystic fibrosis, the Cystic Fibrosis Foundation said it will use a portion of those funds to do something it has never done before: help launch new companies.

The CF Foundation, whose venture philanthropy efforts helped fund Vertex’s line of powerful CF drugs, is teaming with Longwood Fund to create a CF incubator. The incubator will identify new companies with platforms or technologies that can be applied in the rare genetic condition. The partners can then finance early development in exchange for a commitment from the companies to focus on applications in cystic fibrosis.

Kiersten Stead, John Hamer (DCVC Bio)

Deep tech, round 2: DCVC Bio bags $350M fund to chase the tip of the life sci­ence spear

It took one trip from San Francisco to Vancouver for Kiersten Stead and her DCVC Bio crew to feel confident about throwing their weight — and cash — behind AbCellera.

CEO Carl Hansen’s academic background and the potential of the platform, which combined machine vision and robotics with microfluidics, were promising. But the site visit sealed the Series A deal, where DCVC was the lead and only investor.

Igor Splawski (CureVac)

Cure­Vac nabs a top No­var­tis sci­en­tist for CSO slot as mR­NA vac­cines seize the spot­light

One of the key players in the race to develop a new mRNA vaccine to fight Covid-19 has reshuffled the top spots in the executive suite. And they’re bringing in a Novartis vet out of Harvard to spearhead their work on mRNA.

CureVac, which just filed for an IPO that’s still taking shape, has formally handed Franz-Werner Haas the CEO title, after giving it to him on an interim basis. And the still rather stealthy German biotech largely owned by billionaire Dietmar Hopp has recruited Igor Splawski as its chief scientific officer.

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Stephen Hahn, FDA commissioner (AP Images)

FDA touts ad­vanced man­u­fac­tur­ing to ad­dress Covid-19 short­falls

Advanced manufacturing techniques can be employed to help address some of the manufacturing and supply chain problems the US has seen during the Covid-19 pandemic, Stephen Hahn, FDA commissioner, and Anand Shah, FDA deputy commissioner for medical and scientific affairs, wrote in a blog post on the FDA website.

“The potential public health value of advanced manufacturing is even greater in the context of the ongoing COVID-19 pandemic, which has highlighted the strain on supply chains and the need for adaptive manufacturing systems to accelerate the production of medical countermeasures,” Hahn and Shah wrote. “The FDA has established a strong regulatory foundation to support the uptake of advanced manufacturing, and COVID-19 provides the unique impetus to spur further advancement of medical manufacturing.”