Barbara Weber (LinkedIn)

Tan­go Ther­a­peu­tics nabs $60M in CRISPR-based hunt for hid­den can­cer genes

Like a few oth­er CEOs, Bar­bara We­ber emerged from the JP Mor­gan Health­care Con­fer­ence up­beat. She had been test­ing the wa­ters of a Se­ries B for her can­cer start­up, Tan­go Ther­a­peu­tics, since the fall and af­ter a few in­vestor meet­ings in San Fran­cis­co, a lead in­vestor had stepped for­ward, set­ting the stage for a size­able round.

“We just didn’t re­al­ize that in the mid­dle of that we’d end up in a glob­al pan­dem­ic,” We­ber told End­points News. “I won’t lie to you, it was a lit­tle nerve-wrack­ing — when we were just get­ting things sort­ed out and do­ing al­lo­ca­tions, the first mar­ket crash hap­pened.”

To­day, though, Tan­go has emerged with a $60 mil­lion Se­ries B led by Box­er Cap­i­tal and joined by Cor­morant As­set Man­age­ment and Cas­din Cap­i­tal. On top of the $55 mil­lion Se­ries A from Third Rock Ven­tures and a $50 mil­lion deal from Gilead, the new round brings them to a to­tal of $155 mil­lion raised to ad­vance their CRISPR-based ap­proach to find­ing new tar­get­ed can­cer drugs — an ef­fort, We­ber said, that the Covid-19 pan­dem­ic has on­ly pushed back a few weeks.

They were able to shift their re­search ac­cord­ing to where the out­break was.

“We had a lot of work on­go­ing with Chi­nese CROs and we took prob­a­bly a 3-4 week de­lay when Chi­na was re­al­ly locked down,” We­ber said, adding they moved some ex­per­i­ments in-house.   “When we had to shut down they were ac­tu­al­ly com­ing back up.”

Tan­go’s ap­proach is built around a con­cept called syn­thet­ic lethal­i­ty, the con­cept that un­der­girds PARP in­hibitors. Those drugs tar­get a pro­tein in pa­tients with a mu­ta­tion on one of the pro­teins used to re­pair DNA. One mal­func­tion­ing pro­tein leads to er­rors in the DNA that can give rise to can­cer, but if you knock out the oth­er pro­tein, the can­cer cells are so un­able to re­pair its DNA that it dies.

Re­searchers have long sus­pect­ed there were oth­er genes that played sim­i­lar roles but lacked good ways of find­ing them.  Most drugged onco­genes are those that over­ex­pressed, but here you were try­ing to de­tect an ab­sence. (PARPs had been dis­cov­ered es­sen­tial­ly by guess-and-check).

Many in­clud­ing No­var­tis had large pro­grams that used syn­thet­ic RNA to find these, but they proved un­re­li­able, a fact that got wide me­dia at­ten­tion last year af­terSci­ence Trans­la­tion Med­i­cine pub­li­ca­tion.

“There were just way too many false pos­i­tives,” We­ber said. “You could get 200 and then you just have to sort through that and maybe some­times all of them were false.”

To find these genes, Tan­go us­es CRISPR to knock out in­di­vid­ual genes in can­cer cell lines. The genes that, when knocked out, led to cell death are con­sid­ered po­ten­tial drug tar­gets. Tan­go will in the next few months an­nounce their first can­di­date, al­though that one is based on in­sights from a project run at the Broad In­sti­tute. In-house projects are com­ing, We­ber said.

Syn­thet­ic lethal­i­ty, though, is just one of three ap­proach­es Tan­go is tak­ing. A sec­ond in­volves un­marked onco­genes. And a third in­volves search­ing for genes that tu­mors use to tamp down the im­mune sys­tem and it’s what land­ed them a deal with Gilead worth up to $1.7 bil­lion. Find­ing these genes in­volves a sim­i­lar CRISPR-based ap­proach, but is more com­plex be­cause it re­quires an ac­tive im­mune sys­tem.

In oth­er words, you need mice. You en­gi­neer those mice and use CRISPR to knock out genes in vi­vo, a much longer and more repet­i­tive process. Gilead will be work­ing close­ly with Tan­go on these pro­grams, but Tan­go has the rights op­tion on 2 out of 5 of the po­ten­tial drugs that could emerge, part of their long-term goal of be­com­ing a ful­ly in­te­grat­ed biotech.

“As far as we know, we’re the on­ly com­pa­ny with an es­tab­lished plat­form,” We­ber said of their im­mune sup­pres­sion pro­gram, not­ing that a cou­ple of aca­d­e­m­ic cen­ters are do­ing sim­i­lar work. “It’s very new, it’s very la­bor in­ten­sive.”

Bio­mark­er 'roadmap­s' and the fu­ture of can­cer R&D; Cur­tain rais­es on #AS­CO22; Pfiz­er, No­var­tis tack­le drug ac­cess; 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.

While this was not a week for earth-shattering news, there were certainly a lot of interesting tidbits. If you found this recap helpful, please recommend it to your friends and colleagues. We’ll see you on the other side of the long weekend.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,800+ biopharma pros reading Endpoints daily — and it's free.

Keep­ing pres­sure on Am­gen, Mi­rati draws mixed re­views on lat­est cut of KRAS da­ta

As the close runner-up to Amgen’s Lumakras in the KRAS race, any data cut from Mirati’s adagrasib continues to draw scrutiny from analysts. And the latest batch of numbers from ASCO is a decidedly mixed bag.

While a quick comparison suggests that adagrasib spurred slightly more responses and led to a longer overall survival than Lumakras among a group of non-small cell lung cancer patients, its duration of response appears shorter and the safety profile continues to spark concern.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,800+ biopharma pros reading Endpoints daily — and it's free.

Tran­si­tion to new Eu­ro­pean clin­i­cal tri­als in­fo sys­tem starts slow­ly

At the end of January, the European Medicines Agency officially launched its new clinical trials info system (CTIS), although the migration to the new platform has only really just begun, and sponsors have until the end of January 2023 before all initial trial applications must be submitted through CTIS.

Overall, 56 clinical trial applications have been submitted in CTIS during the first 3 months since the launch of the system on Jan. 31, according to new data posted by the EMA. By comparison, about 4,000 new trials are authorized each year across Europe.

Ann is one of ViiV Healthcare's newest spokespeople as the retired school administrator speaks up about her HIV status.

GSK's Vi­iV de­buts next evo­lu­tion in HIV med Dova­to cam­paign with new spokes­peo­ple and new mes­sage

When Ann saw the first TV commercials for HIV medicine Dovato, she didn’t see herself represented. So the 74-year-old retired school administrator who’s been living with HIV since 1998, reached out to GSK’s ViiV Healthcare and asked why not?

Now Ann is one of three people starring in ViiV’s latest Dovato campaign called “Detect This.” The next-step evolution in the branded campaign plays on the word “detect” — often used in describing HIV status under control as undetectable — but in this case, uses the word as a directive for people to understand they can use fewer medicines.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,800+ biopharma pros reading Endpoints daily — and it's free.

Switzer­land to de­stroy over 600,000 ex­pired dos­es of Mod­er­na Covid vac­cine

As concerns related to uptake and distribution continue to linger, Switzerland is among the first countries that plans to destroy hundreds of thousands of expired and unused Covid-19 vaccine doses.

The European country said it plans to destroy more than 600,000 doses of Moderna’s Spikevax Covid-19 vaccine as the doses have reached their expiration date.

However, Moderna CEO Stéphane Bancel told the World Economic Forum in Davos, Switzerland that he’s in the process of throwing 30 million doses in the garbage, exclaiming, “We have a big demand problem.”

AS­CO ab­stracts mint some ear­ly win­ners, but Io­vance, Spring­Works get hit by mas­sive loss­es

Before cancer-focused biotechs start their trek to the first in-person American Society of Clinical Oncology (ASCO) annual conference since the pandemic began, investors have taken a good look at the teasers for the data scheduled to be presented — and started placing bets.

With its power to confer overnight fame, ASCO is a stage where impressive or surprise debut performances can go a long way. On the other hand, disappointing details could be punishing.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,800+ biopharma pros reading Endpoints daily — and it's free.

Nassim Usman, Catalyst Biosciences CEO

Af­ter $60M Ver­tex deal, group of Cat­a­lyst share­hold­ers claims biotech could’ve sold as­sets three years ago

Catalyst Biosciences was down to five employees in March, and the biotech needed to do something after two rounds of layoffs, a nixed collaboration and a culling of its hemophilia program.

In came Vertex, with $60 million to buy up the South San Francisco biotech’s preclinical complement drugs, which target the system that bridges the body’s innate and adaptive immune response and a class most known for Ultomiris and Soliris. The deal includes CB 2782-PEG, the dry AMD drug that Biogen no longer wanted in March.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,800+ biopharma pros reading Endpoints daily — and it's free.

Levi Garraway, Roche CMO (Genentech)

Roche's CD20xCD3 does­n't beat Gen­mab at ORR, but sets bar for CR da­ta on lym­phoma drug

On its way to potentially becoming the first to market with a CD20xCD3 bispecific for aggressive lymphoma, Big Pharma’s largest R&D spender has some more data to pad its case with an FDA filing slated for later this year.

Roche dropped some more details from a Phase II expansion study of its fixed-duration glofitamab, to be presented at next week’s ASCO annual meeting, in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). The patients had received a median of three prior therapies.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,800+ biopharma pros reading Endpoints daily — and it's free.

Lina Khan, FTC chair (Graeme Jennings/Pool via AP Images)

Pile-on over PBMs con­tin­ues with FTC com­ments and a new bi­par­ti­san Sen­ate bill

More than 500 stakeholders sent comments to the FTC on whether the commission should look further into pharma middlemen, known as PBMs, with many of the commenters calling for more federal oversight.

Similar to the critical open comment period in a deadlocked FTC session last February, pharmacies and pharmacy groups are continuing to call out the lack of transparency among the top 3 PBMs, which control about 80% of the market.