At­las and Or­biMed back Boston's Kyn in $49M round to pur­sue im­munome­tab­o­lism ther­a­pies

Boston biotech Kyn Ther­a­peu­tics has raised $49 mil­lion in a Se­ries A round to ad­vance its im­munome­tab­o­lism ther­a­pies to treat can­cer.

The mon­ey comes from At­las Ven­ture and Or­biMed — both re­peat in­vestors who first fund­ed the com­pa­ny dur­ing its launch last March.

Mark Man­fre­di

Kyn is led by an At­las en­tre­pre­neur-in-res­i­dence Mark Man­fre­di, who was pre­vi­ous­ly chief sci­en­tif­ic of­fi­cer at Raze Ther­a­peu­tics (al­so an At­las-fund­ed start­up). Raze raised a $24 mil­lion Se­ries A in 2014, but the com­pa­ny ap­pears to have wound down pret­ty quick­ly. The web­site is no longer ac­tive, and Man­fre­di said Raze still has some as­sets and col­lab­o­ra­tions, but no longer em­ploys any­one. At­las’ Bruce Booth says the un­der­ly­ing can­cer me­tab­o­lism bi­ol­o­gy was too com­pli­cat­ed to war­rant fur­ther in­vest­ment. Be­fore Raze, Man­fre­di was VP of on­col­o­gy bi­ol­o­gy at Take­da.

Now as CEO of Kyn, Man­fre­di is once again lead­ing a com­pa­ny fo­cused on im­munome­tab­o­lism to treat can­cer, a grow­ing area of im­muno-on­col­o­gy. The field lever­ages meta­bol­ic path­ways and the bro­ken-down mol­e­cules that re­sult from me­tab­o­lism (called metabo­lites). Kyn has an undis­closed num­ber of pre­clin­i­cal pro­grams de­signed to re­verse the ef­fects of metabo­lites pro­mot­ed by can­cer cells.

First, the com­pa­ny is tar­get­ing the IDO and TDO path­ways. IDO and TDO are meta­bol­ic en­zymes over­ex­pressed in many can­cers that con­vert tryp­to­phan to kynure­nine. Kynure­nine ac­cu­mu­lates in and around the tu­mor where it en­ters im­mune cells and binds the aryl hy­dro­car­bon re­cep­tor. This trig­gers the broad sup­pres­sion of the im­mune sys­tem, Man­fre­di said.

Kyn’s plan is to de­grade kynure­nine and/or an­tag­o­nise the aryl hy­dro­car­bon re­cep­tor.

The IDO path­way is al­ready be­ing eyed up by oth­er com­pa­nies, in­clud­ing In­cyte, Bris­tol-My­ers, and NewLink Ge­net­ics. But Man­fre­di tells me he thinks it’s im­por­tant to tar­get TDO, as well.

“The in­hibitors out there on­ly in­hib­it IDO,” Man­fre­di said. “Some tu­mors ex­press IDO, but oth­ers ex­press TDO as well, which al­so pro­duces the sup­pres­sive metabo­lite kynure­nine. We think if we go af­ter that metabo­lite specif­i­cal­ly, it will be more ef­fec­tive.”

Kyn plans to test their prod­uct can­di­dates as sin­gle agents, as well as in com­bi­na­tion stud­ies with check­point in­hibitors.

Of the com­pa­ny’s new $49 mil­lion, $28 mil­lion is go­ing to fu­el these pro­grams. Man­fre­di said the com­pa­ny isn’t dis­clos­ing which can­cers it’s tack­ling.

The rest of the cash is go­ing to Kyn’s af­fil­i­ate called Ar­rys Ther­a­peu­tics, which has ex­clu­sive­ly con­tract­ed Kyn to de­vel­op ARY-007. This pro­gram does not tar­get IDO/TDO, but is still in the im­munome­tab­o­lism field. The prod­uct can­di­date blocks the EP4 re­cep­tor, which is in­volved in the prostaglandin E2 path­way. ARY-007 has al­ready shown fa­vor­able ther­a­peu­tic char­ac­ter­is­tics in hu­man tri­als for os­teoarthrit­ic pain, Man­fre­di said.

The com­pa­ny is jump­ing in­to Phase Ib stud­ies in 2018.

Part club, part guide, part land­lord: Arie Bellde­grun is blue­print­ing a string of be­spoke biotech com­plex­es in glob­al boom­towns — start­ing with Boston

The biotech industry is getting a landlord, unlike anything it’s ever known before.

Inspired by his recent experiences scrounging for space in Boston and the Bay Area, master biotech builder, investor, and global dealmaker Arie Belldegrun has organized a new venture to build a new, 250,000 square foot biopharma building in Boston’s Seaport district — home to Vertex and a number of up-and-coming biotech players.

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Novotech CRO Ex­pands Chi­na Team as Biotech De­mand for Clin­i­cal Tri­als In­creas­es up to 79%

An increase in demand of up to 79% for clinical trials in China has prompted Novotech the Asia-Pacific CRO to rapidly expand the China team, appointing expert local clinical executives to their Shanghai and Hong Kong offices. The company is planning to expand their team by 30% over the next quarter.

Novotech China has seen considerable demand recently which is borne out by research from GlobalData:
A global migration of clinical research is occurring from high-income countries to low and middle-income countries with emerging economies. Over the period 2017 to 2018, for example, the number of clinical trial sites opened by biotech companies in Asia-Pacific increased by 35% compared to 8% in the rest of the world, with growth as high as 79% in China.
Novotech CEO Dr John Moller said China offers the largest population in the world, rapid economic growth, and an increasing willingness by government to invest in research and development.
Novotech’s 23 years of experience working in the region means we are the ideal CRO partner for USA biotechs wanting to tap the research expertise and opportunities that China offers.
There are over 22,000 active investigators in Greater China, with about 5,000 investigators with experience on at least 3 studies (source GlobalData).

UP­DAT­ED: With loom­ing ‘apoc­a­lypse of drug re­sis­tance,’ Mer­ck’s com­bi­na­tion an­tibi­ot­ic scores FDA ap­proval on two fronts

Merck — one of the last large biopharmaceuticals companies in the beleaguered field of antibiotic drug development — on Wednesday said the FDA had sanctioned the approval of its combination antibacterial for the treatment of complicated urinary tract and intra-abdominal infections.

To curb the rise of drug-resistant bacteria and maintain the efficacy of the therapy, Recarbrio (and other antibacterials) — the drug must be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible gram-negative bacteria, Merck $MRK said.

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John McHutchison in 2012. Getty Images

The $1.1M good­bye: Gilead CSO John McHutchi­son is out as Daniel O’Day shakes up the se­nior team

Just a little more than a year after John McHutchison grabbed a promotion to become CSO at Gilead in the wake of Norbert Bischofberger’s exit, he’s out amid a shakeup of the senior team that is also triggering the departure of two other top execs.

Gilead stated that McHutchison “has decided to step down” from the job as of August 2nd. And their SEC filing notes that he’ll be getting a $1.1 million check to settle up on his contract.

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Thomas Gajewski, David Steinberg. (CRI, Pyxis)

Bay­er, Long­wood back star re­searcher's deep dive in­to the tu­mor mi­croen­vi­ron­ment for new I/O tar­gets

From PD-1 targeting to the RAS pathway to the STING complex, Thomas Gajewski has spent the past two decades of his career decoding the various ways the immune system can be unleashed to defend against cancer. So when the University of Chicago professor comes around to putting all his findings into a new platform for finding new targets, VCs and pharma groups alike pay attention.

“He’s been studying T cells for 20 years, plus he’s one of the world’s leaders if not the world leader in the space,” David Steinberg, partner at Longwood Fund, said. “Furthermore, let me add he did a lot of the foundational research and also some of the seminal clinical trials in the existing set of I/O agents. He understands the space really well, he understands the current strengths, and I think he understood really well what was missing, so he knew where to look.”

Kamala Harris speaking yesterday at the Des Moines Register Iowa Presidential Candidate Forum [via Getty]

Who’s the tough­est on drug prices? A game of po­lit­i­cal one-up­man­ship is dri­ving the pol­i­cy de­bate in Wash­ing­ton

Earlier this week we got a look at Senator Kamala Harris’ position on drug prices. She’s proposing that HHS take an average price from single-payer systems like the UK, Germany and Canada — which leverage market access for lower prices — and use that to set the US price. Anything drug companies collect above that would be taxed at a rate of 100%.

And the rhetoric is scathing:
While families struggle to make it to the end of the month, pharmaceutical companies are turning record profits. They’re spending nearly as much on advertising as R&D. They’re manipulating their market power to hike prices on lifesaving generic drugs. They’re making twice the profit of the average industry in America and still increased drug prices by 10.5% over the past six months alone. Meanwhile, they are charging dramatically higher prices to American consumers.
That’s an escalation on Joe Biden’s plan, which includes drug importation from those cheaper markets as well as allowing Medicare to negotiate prices — something that virtually all Dems agree on now.

H1 analy­sis: The high-stakes ta­ble in the biotech deals casi­no is pay­ing out some record-set­ting win­nings

For years the big trend among dealmakers at the major players has been centered on ratcheting down upfront payments in favor of bigger milestones. Better known as biobucks for some. But with the top 15 companies competing for the kind of “transformative” pacts that can whip up some excitement on Wall Street, with some big biotechs like Regeneron now weighing in as well, cash is king at the high stakes table.

We asked Chris Dokomajilar, the head of DealForma, to crunch the numbers for us, looking over the top 20 deals for the past decade and breaking it all down into the top alliances already created in 2019. Gilead has clearly tipped the scales in terms of the coin of the bio-realm, with its record-setting $5 billion upfront to tie up to Galapagos’ entire pipeline.

Dokomajilar notes:

We’re going to need a ‘three comma club’ for the deals with over $1 billion in total upfront cash and equity. The $100 million-plus club is getting crowded at 164 deals in the last decade with new deals being added towards the top of the chart. 2019 already has 14 deals with at least $100 million in upfront cash and equity for a total year-to-date of over $9 billion. That beats last year’s $8 billion and sets a record.

Add upfronts and equity payments and you get $11.5 billion for the year, just shy of last year’s record-setting $11.8 billion.

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Takeda's trans­la­tion­al cell ther­a­py group revs up for a race to the clin­ic with off-the-shelf CAR-T

Four years after Takeda launched a wide-ranging induced pluripotent stem cell project with the researchers at Nobel prize-winning Shinya Yamanaka’s lab at the University of Kyoto, the pharma company is taking delivery of the first of what it hopes will be a whole pipeline of iPS cell-derived therapies that can deliver on the promise of off-the-shelf CAR-T therapies.

From here, Stefan Wildt — the head of pharma sciences and translational cell therapy at Takeda — and his group of 100-plus scientists will be charged with steering their way to the clinic as they build out the manufacturing and support work for this pipeline-in-the-making. 

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Go­ing in­side cells, Sung Joo Lee has sketched some big goals for his small — but glob­al — team of drug hunters

For a small biotech based in South Korea with a research arm in Cambridge, MA, Orum Therapeutics has sketched out some big goals aimed at developing antibodies for intracellular targets. And now they have a new $30 million round to push the work forward, aiming at a slate of currently undruggable quests.

Orum has been working on a platform tech out of Ajou University that relies on endocytosis to smuggle antibodies and their cargo inside a cell. They’ve published work in Nature that illustrates its preclinical potential in RAS mutations, and KRAS is on their list of targets. 

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