In 2010, Nick Sireau quit his job to fo­cus sole­ly on the pa­tient group he had set up to help his sons di­ag­nosed with a rare ge­net­ic dis­ease called alka­p­tonuria (AKU). Re­searchers had found a fea­si­ble treat­ment from an un­like­ly source: a weed­killer, but it was be­ing used to help in­fants with a dif­fer­ent dis­or­der. Sireau would then con­front the per­ils of the tra­di­tion­al tri­al-and-er­ror drug dis­cov­ery process that de­mands time and mon­ey.

Tim Guil­liams

In 2014, two sci­en­tists met Sireau, who had been fierce­ly lob­by­ing and fundrais­ing to get UK au­thor­i­ties to tri­al the com­pound in pa­tients with AKU. The en­counter sparked the two re­searchers — the British sci­en­tist be­hind Vi­a­gra, David Brown, and a bio­engi­neer from Cam­bridge, Tim Guil­liams — to work on mar­ry­ing the con­cept of drug re­pur­pos­ing with AI and ma­chine learn­ing, par­tic­u­lar­ly for rare con­di­tions. Soon, their com­pa­ny — Healx — was born.

This Ju­ly, the Cam­bridge, UK-based com­pa­ny raised $10 mil­lion in a Se­ries A round of fund­ing. On Wednes­day, Healx un­veiled a fresh $56 mil­lion in­jec­tion — as it preps for a Phase IIa clin­i­cal tri­al ex­pect­ed to ini­ti­ate in the first quar­ter of 2020 — in pa­tients with Frag­ile X syn­drome, a con­di­tion that spawns de­vel­op­men­tal prob­lems and is con­sid­ered the lead­ing ge­net­ic cause of autism.

The tri­al will eval­u­ate the safe­ty and ef­fi­ca­cy of a com­bi­na­tion ther­a­py, Guil­liams told End­points News, de­clin­ing to pro­vide fur­ther de­tail.

“If you look at com­bi­na­tions of two or three drugs, you have about 13 bil­lion pos­si­bil­i­ties per dis­ease — so how do you se­lect the top 10, the top 20? And we don’t go be­yond that,” Guil­liams said. Healx’s AI plat­form claims to short­en the dis­cov­ery-to-clin­ic time­line to as lit­tle as 24 months.

David Brown

Healx’s ap­proach does not lean on an ini­tial hy­poth­e­sis. “We let the al­go­rithm de­cide which dis­eases we’re go­ing to work on, which drugs are be­ing matched. And then we work out a mech­a­nism or hy­poth­e­sis af­ter­wards,” he said.

So far, Healx has launched 10 pre­clin­i­cal pro­grams across a pletho­ra of in­di­ca­tions — of which four (in­clud­ing the Frag­ile X pro­gram) have reaped re­sults so far, Guil­liams said, not­ing that each of these read­outs has been pos­i­tive. With this Se­ries B, the plan is to launch an­oth­er 40 pre­clin­i­cal pro­grams, he added.

If they are suc­cess­ful — with any of these shots on goal — the plan is to make sure pric­ing is not in the typ­i­cal or­phan drug price range which hov­ers around $240,000 per pa­tient per year, Guil­liams said.

Re­pur­pos­ing drugs on pur­pose (or by ac­ci­dent) has yield­ed some suc­cess — that the process in­volves large­ly de-risked com­pounds, low­er de­vel­op­men­tal costs, and briefer time­lines doesn’t hurt ei­ther.

Vi­a­gra is, of course, the most heav­i­ly cit­ed ex­am­ple. The drug, known chem­i­cal­ly as silde­nafil, was orig­i­nal­ly be­ing test­ed as a treat­ment for coro­nary hy­per­ten­sion — but a pesky side ef­fect felt by pa­tients in tri­als led to its even­tu­al ap­proval as an erec­tile dys­func­tion drug.

Then there’s the seda­tive thalido­mide — which gained no­to­ri­ety af­ter its link to se­vere skele­tal birth de­fects trig­gered its with­draw­al in 1957. How­ev­er, years lat­er it was deemed ef­fec­tive as a can­cer treat­ment, even breed­ing the de­vel­op­ment and ap­proval of even more suc­cess­ful de­riv­a­tives, such as Cel­gene’s block­buster Revlim­id.

Mean­while, Mer­ck’s Vioxx — which was un­cer­e­mo­ni­ous­ly tak­en off shelves af­ter its link to dou­bling pa­tients’ risk of heart at­tack and stroke emerged — could resur­face as a gener­ic treat­ment for a side ef­fect ex­pe­ri­enced by he­mo­phil­ia pa­tients. The gener­ic ver­sion is be­ing prepped for a piv­otal tri­al slat­ed to be­gin next year.

But akin to tra­di­tion­al drug de­vel­op­ment, drug re­pur­pos­ing has al­so seen its share of set­backs. Two ex­am­ples of late-stage fail­ures in­clude the bid to use the an­ti­his­t­a­mine, la­trepir­dine, as a treat­ment for Hunt­ing­ton’s dis­ease, as well as the pur­suit of re­pur­pos­ing the an­tibi­ot­ic, cef­tri­ax­one, as a med­i­cine for ALS.

Healx’s Se­ries B was led by Eu­ro­pean VC firm Atom­i­co and joined by Glob­al Brain and btov Part­ners. All pre­vi­ous in­vestors, in­clud­ing Balder­ton Cap­i­tal, Amadeus Cap­i­tal Part­ners and Jonathan Mil­ner, al­so par­tic­i­pat­ed in the round.

Healx did not ini­tial­ly plan to raise more mon­ey this year, but in­ter­est in their ap­proach bal­looned giv­en their progress, Guil­liams said. “I think that’s a re­al­ly good sign for the in­vest­ment land­scape in the UK and Eu­rope be­cause for Eu­rope it’s a pret­ty large B round…com­pared to the US.”

“And I’m won­der­ing if part of that is let’s make sure we in­vest be­fore Brex­it kicks in.”

Despite worries about regulatory delays due to new work arrangements under Covid-19, the FDA appears intent to go full speed ahead with its everyday work, not only granting priority review to a stem cell therapy for acute graft versus host disease but also plotting an advisory committee meeting for it.

With a PDUFA date of September 30, the journey of the drug — remestemcel-L, or Ryoncil — could shed light on the agency’s capacity to facilitate drug development unrelated to Covid-19.

→ Flexion may be hitting the brakes on clinical trials, including one for its osteoporosis Zilretta, but that’s not stopping the biotech from plotting regulatory action in China. Hong Kong Tainuo has committed $10 million upfront to seize the development and commercialization rights to Zilretta, with plans to apply for a clinical trial in China by the end of the year. Flexion, which said it has 10 months of finished goods in the US and 12 months of active pharmaceutical ingredient available, will supply all products to the Chinese partner.