Nancy Yu (RDMD)

Abun­dant fund­ing, sparse da­ta: San Fran­cis­co start­up backs 're­al world' mod­el for rare dis­ease drug de­vel­op­ment

Rare dis­eases, a field of drug de­vel­op­ment where fund­ing far out­strips re­search on of­ten poor­ly un­der­stood con­di­tions, can leave sci­en­tists of­ten rein­vent­ing the wheel to en­gi­neer ther­a­peu­tics.

RD­MD, a San Fran­cis­co-based com­pa­ny, has a plan to ad­dress that im­passe by serv­ing as a con­duit be­tween the pa­tient and the drug de­vel­op­er. The plat­form courts pa­tients with rare dis­eases by help­ing them ac­cess med­ical records and par­tic­i­pate in re­search, while for drug de­vel­op­ers, the com­pa­ny struc­tures the com­piled da­ta in an ef­fort to build re­search pro­grams and de­vel­op an ev­i­dence base palat­able for reg­u­la­to­ry au­thor­i­ties.

Un­til now, com­pa­nies big and small in the space have been stuck look­ing for pa­tients in 10, 20 or more hos­pi­tals, de­pend­ing on the dis­ease, not­ed co-founder Nan­cy Yu in an in­ter­view.

“So most com­pa­nies are grow­ing their in­ter­nal teams, as well as work­ing with con­tract re­search or­ga­ni­za­tions, and sub­con­tract­ing to up to some­times 15 dif­fer­ent soft­ware ven­dors to man­age the process,” Yu said.

Stream­lin­ing this process, and help­ing pa­tients them­selves ac­cess their da­ta and par­tic­i­pate in re­search, could change the way the rare dis­ease drug de­vel­op­ment is con­duct­ed, RD­MD hopes. This lofty goal was giv­en a $14 mil­lion in­jec­tion on Thurs­day in a Se­ries A round led by Spark Cap­i­tal, a ven­ture cap­i­tal firm that has pre­vi­ous­ly backed com­pa­nies such as Slack, Twit­ter and Ocu­lus.

“At the end of the day, rare dis­ease just re­quires a dif­fer­ent mod­el for drug de­vel­op­ment,” Yu said. “The chal­lenge is re­al­ly un­der­stand­ing what the dis­ease ac­tu­al­ly is and how you can best cre­ate and de­sign a pro­gram around ev­i­dence that ex­ists. It’s re­al­ly hard to de­sign a suc­cess­ful pro­gram if you don’t know much about the dis­ease.”

That re­quires pa­tient da­ta which, apart from be­ing scarce, are not all ac­ces­si­ble in one uni­ver­sal elec­tron­ic med­ical records sys­tem.

“So we get per­mis­sion from pa­tients … to be able to get all their records from their var­i­ous fa­cil­i­ties. And that’s both be­cause we want to em­pow­er pa­tients with that choice of opt­ing in to par­tic­i­pate in re­search, but it’s al­so a ne­ces­si­ty op­er­a­tional­ly for us to be able to get that in­for­ma­tion, be­cause it doesn’t sit in a cen­tral data­base some­where,” she said.

With the pa­tient’s con­sent, the da­ta are then col­lat­ed and dis­sem­i­nat­ed to com­pa­nies to give them a com­pre­hen­sive un­der­stand­ing of the dis­ease, and con­se­quent­ly, de­sign clin­i­cal tri­als, de­ter­mine what end­points and bio­mark­ers are rel­e­vant, and even ed­u­cate pay­ers and in­sur­ance com­pa­nies so they can cov­er the drugs up­on ap­proval.

There’s a lot that pa­tients can con­tribute to in terms of re­search that doesn’t nec­es­sar­i­ly in­volve par­tic­i­pat­ing in a clin­i­cal tri­al, she added.

“For ex­am­ple, some of this da­ta could be used to sup­port and elim­i­nate the need for a place­bo con­trol arm be­cause you’re just look­ing at da­ta that al­ready ex­ists in the re­al world around pa­tients and their nat­ur­al pro­gres­sion of dis­ease,” Yu said. “And so that’s cer­tain­ly some­thing that every­one is very fo­cused on and hop­ing to use the da­ta for.”

Sound fa­mil­iar? A New York-based tech com­pa­ny called Flat­iron Health that was swal­lowed by Swiss gi­ant Roche in 2018, has sim­i­lar plans to use re­al-world ev­i­dence to re­place more tra­di­tion­al clin­i­cal tri­al da­ta to help the FDA make de­ci­sions for can­cer drugs.

But tra­di­tion­al ran­dom­ized con­trolled tri­als (RCTs) are con­sid­ered the gold stan­dard to prove if a com­pound or in­ter­ven­tion is safe and ef­fec­tive for its in­tend­ed use — they are used to show that a ben­e­fit or ad­verse event ob­served is not a mat­ter of chance or bias.

But giv­en lim­i­ta­tions such as strict in­clu­sion cri­te­ria, which typ­i­cal­ly dis­qual­i­fy old­er pa­tients and those suf­fer­ing from co-mor­bidi­ties, RCTs can be an in­ac­cu­rate rep­re­sen­ta­tion of pa­tients in the re­al world. But skep­tics crit­i­cize that re­ly­ing sole­ly on re­al-world ev­i­dence could be dan­ger­ous, as the process has the po­ten­tial to in­tro­duce re­searcher bi­as­es, and is not sub­ject to the same method­olog­i­cal rig­or.

That be­ing said, un­like can­cer drug de­vel­op­ment, rare dis­ease tri­als are of­ten ham­pered by slow en­roll­ment due to the scarci­ty of pa­tients — and the FDA re­quires a much small­er body of ev­i­dence for de­ci­sion mak­ing. Sarep­ta Ther­a­peu­tics’ pi­o­neer­ing Duchenne mus­cu­lar dy­s­tro­phy (DMD) drug Ex­ondys 51, for in­stance, was ap­proved on the ba­sis of a tiny non-place­bo con­trolled tri­al that com­pared the ef­fect of the drug to the nat­ur­al course of the dis­ease.

De­spite stiff op­po­si­tion from with­in and out­side the agency from crit­ics who said da­ta were in­suf­fi­cient to war­rant ap­proval, the FDA cleared the drug for use in a sub­set of pa­tients with the rare mus­cle-wast­ing dis­ease in 2016, prompt­ing some to sug­gest the agency had bowed to pres­sure from pa­tient ad­vo­cates. On­ly in 2019 did Sarep­ta sub­mit plans for a con­fir­ma­to­ry tri­al, which is ex­pect­ed to be com­plet­ed by 2024. But in the mean­time, the com­pa­ny has since se­cured an­oth­er DMD ap­proval on the ba­sis of a 24 pa­tient study.

Yu, who pre­vi­ous­ly worked with con­sumer ge­net­ics com­pa­ny 23andme, set up RD­MD in late 2017 soon af­ter co-founder On­no Faber was di­ag­nosed with a rare ge­net­ic dis­ease called NF2 (Neu­rofi­bro­mato­sis Type 2), which af­fects 1 in 30,000 peo­ple.

“And so when we got to­geth­er, it was re­al­ly to fig­ure out how do we tack­le this — there are 7000 con­di­tions and like one in 10 peo­ple have a rare dis­ease that in ag­gre­gate, it’s a re­al­ly big prob­lem,” she not­ed.

On Thurs­day, the com­pa­ny al­so un­veiled a part­ner­ship with Bel­gium-based drug­mak­er UCB for up to five years to work on pro­gres­sive supranu­clear pal­sy (PSP), a rare neu­rode­gen­er­a­tive dis­ease.

In ad­di­tion, RD­MD is al­so part­ner­ing with pa­tient ad­vo­ca­cy or­ga­ni­za­tions and physi­cian con­sor­tiums across 12 con­di­tions, in­clud­ing the Chil­dren’s Tu­mor Foun­da­tion, Cure San­fil­ip­po Foun­da­tion and Na­tion­al Tay-Sachs & Al­lied Dis­eases As­so­ci­a­tion.

The Se­ries A round al­so in­clud­ed the par­tic­i­pa­tion of ex­ist­ing seed in­vestors Lux Cap­i­tal, Vil­lage Glob­al and Garu­da Ven­tures, and new in­vestor Maveron. The mon­ey will be used, among oth­er things, to ex­pand in­to a fur­ther 20 rare con­di­tions and en­sure the con­ti­nu­ity of re­search pro­grams through­out the Covid-19 pan­dem­ic.

Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

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

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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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Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

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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?

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RA Cap­i­tal, Hill­house join $310M rush to back Ever­est's climb to com­mer­cial heights in Chi­na

Money has never been an issue for Everest Medicines. With an essentially open tab from their founders at C-Bridge Capital, the biotech has gone two and a half years racking up drug after drug, bringing in top exec after top exec, and issuing clinical update after update.

But now other investors want in — and they’re betting big.

Everest is closing its Series C at $310 million. The first $50 million comes from the Jiashan National Economic and Technological Development Zone; the remaining C-2 tranche was led by Janchor Partners, with RA Capital Management and Hillhouse Capital as co-leaders. Decheng Capital, GT Fund, Janus Henderson Investors, Rock Springs Capital, Octagon Investments all joined.

Por­tion of Neil Wood­ford’s re­main­ing in­vest­ments, in­clud­ing Nanopore, sold off for $284 mil­lion

It’s been precisely one year and one day since Neil Woodford froze his once-vaunted fund, and while a global pandemic has recently shielded him from the torrent of headlines, the fallout continues.

Today, the California-based patent licensing firm Acacia Research acquired the fund’s shares for 19 healthcare and biotech companies for $284 million.  Those companies include shares for public and private companies and count some of Woodford’s most prominent bio-bets, such as Theravance Biopharma, Oxford Nanopore and Mereo Biopharma, according to Sky News, which first reported the sale. It won’t include shares for BenevelontAI, the machine learning biotech once valued at $2 billion.