Big Phar­ma VC firms put $11M in seed funds be­hind can­cer start­up with bold vi­sion

The ven­ture arms of three Big Phar­mas have jumped in to seed a Swiss can­cer start­up with a bold twist on tar­get­ed ther­a­py that, the founders say, could have ef­fects on vir­tu­al­ly every type of can­cer.

No­var­tis Ven­tures, Pfiz­er Ven­tures and Mer­ck’s M Ven­tures, along with Omega and LSP, have seed­ed FoRx Ther­a­peu­tics with €10 mil­lion ($11 mil­lion). The biotech, found­ed by syn­thet­ic bi­ol­o­gy pi­o­neer Thanos Ha­la­zonetis, will look to tar­get and dis­rupt a DNA re­pair mech­a­nism he dis­cov­ered sev­er­al years ago and that, he said,  al­most all can­cers re­ly on to pro­lif­er­ate.

“This is a fea­ture of al­most all can­cers,” Ha­la­zonetis told End­points News. “Nor­mal cells are not af­fect­ed.”

Thanos Ha­la­zonetis

The com­pa­ny re­lies on a con­cept known as syn­thet­ic lethal­i­ty. Gen­er­al­ly, that refers to when a par­tic­u­lar mu­ta­tion helps gives rise to can­cer but al­so makes that can­cer re­liant on cer­tain process­es that nor­mal cells don’t re­ly on. The most fa­mous ex­am­ple is PARP in­hibitor. Pa­tients with mu­ta­tions in a DNA re­pair en­zyme called BR­CA1 or BR­CA2 are prone to can­cer. Be­cause those can­cer cells, though, are miss­ing one func­tion­ing DNA re­pair en­zyme, they be­come re­liant on a dif­fer­ent one, called PARP, to prop­er­ly repli­cate.

New biotechs, such as Third Rock Ven­ture’s Tan­go Ther­a­peu­tics, are us­ing tech­nol­o­gy like CRISPR screens to find new pairs of genes that are sim­i­lar­ly linked.

FoRx, though, is go­ing af­ter a path­way they say vir­tu­al­ly all can­cer cells re­ly on, called the break-in­duced repli­ca­tion path­way. Ba­si­cal­ly, nor­mal healthy cells be­gin DNA repli­ca­tion at pre­cise points on the dou­ble he­lix. Can­cers with onco­genes, though, in their rush to prop­a­gate as fast as pos­si­ble, start at the wrong point. Strands that be­gin copy­ing them­selves at the wrong point even­tu­al­ly bump up against the rest of the tran­scrip­tion­al ma­chin­ery, col­li­sions that in­ter­fere with their abil­i­ty to copy.

“It’s like some­one try­ing to run too fast and they trip and fall down,” Ha­la­zonetis said.

Can­cer cells can sur­vive this, though, be­cause all cells have pro­teins to fix the dam­age wrought when DNA re­pairs at the wrong start­ing point. FoRx plans to block those pro­teins. Ha­la­zonetis said this should kill can­cer cells but should have lit­tle ef­fect on healthy cells, who rarely need to use this method of re­pair­ing their DNA.

“As far as we know, there are no oth­er biotechs fo­cus­ing on this,” Vin­cent Os­sipow, a part­ner at Omega and a FoRx board mem­ber, told End­points.

Os­sipow com­pared this in­vest­ment to Omega’s past ef­forts to get in on the ground floor of new can­cer re­search, in­clud­ing with bis­pe­cif­ic an­ti­bod­ies and on­colyt­ic virus­es.

Ha­la­zonetis first pub­lished on the dis­cov­ery of the path­way in Na­ture in 2005, and fur­ther on how it works and might be drugged in 2014 in Sci­ence, and again in Na­ture in 2018. Be­cause the path­way is used by vir­tu­al­ly all can­cers, Ha­la­zonetis sug­gest­ed that it should not lead to the re­sis­tance most oth­er tar­get­ed can­cer ther­a­pies even­tu­al­ly give rise to.

The spe­cif­ic com­pounds the FoRx might use, though, re­main un­der wraps. They hope to bounce a tar­get in the next 18-24 months and be in the clin­ic 12-18 months af­ter that. They will go first af­ter can­cers that lack good tar­get­ed op­tions, such as colon can­cer, with the goal of be­com­ing lead­ers in syn­thet­ic lethal­i­ty.

“It’s a hot but not yet crowd­ed land­scape,” Therese Maria Liecht­en­stein of M Ven­tures told End­points. “Thanos is a pi­o­neer.”

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

Covid-19 roundup: Mod­er­na read­ies to en­ter PhI­II in Ju­ly, As­traZeneca not far be­hind; EU ready to ne­go­ti­ate vac­cine ac­cess with $2.7B fund

Moderna may soon add another first to the Covid-19 vaccine race.

In March, the mRNA biotech was the first company to put a Covid-19 vaccine into humans. Next month, they may become the first company to put their vaccine into the large, late-stage trials that are needed to prove whether the vaccine is effective.

In an interview with JAMA editor Howard Bauchner, NIAID chief Anthony Fauci said that a 30,000-person, Phase III trial for Moderna’s vaccine could start in July. The news comes a week after Moderna began a Phase II study that will enroll several hundred people.

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José Basel­ga finds promise in new class of RNA-mod­i­fy­ing can­cer tar­gets, lock­ing in 3 pre­clin­i­cal pro­grams with $55M

Having dived early into some of the RNA breakthroughs of the last decades — betting on Moderna’s mRNA tech and teaming up with Silence on the siRNA front — AstraZeneca is jumping into a new arena: going after proteins that modify RNA.

Their partner of choice is Accent Therapeutics, which is receiving $55 million in upfront payment to steer a selected preclinical program through to the end of Phase I. After AstraZeneca takes over, the Lexington, MA-based startup has the option to co-develop and co-commercialize in the US — and collect up to $1.1 billion in milestones in the long run. The deal also covers two other potential drug candidates.

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Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

Caught in a stand­off with its con­tract man­u­fac­tur­er over Covid-19 vac­cine, In­ovio files suit in an at­tempt to break free while ri­vals race ahead

Inovio was one of the first vaccine developers to snag attention for a jab that their execs said promised to end the Covid-19 pandemic. Using their own unique DNA tech, CEO Joseph Kim said it took just 3 hours to work it out.

But while rivals are racing to the finish line with ambitious plans to make vast quantities of their vaccines with billions of dollars of deals, Inovio is still stuck at the starting line on manufacturing.