Richard DiMarchi, MBX Biosciences

Suc­cess­ful sci­en­tist-in­vestor al­lies team up again — this time for a stab at rare meta­bol­ic dis­ease

A sci­en­tist-ex­ec­u­tive team that, over the last decade, sold one di­a­betes biotech to Roche for up-to $537 mil­lion and two oth­ers to No­vo Nordisk for undis­closed sums are back with a new com­pa­ny.

Kent Hawry­luk

Uni­ver­si­ty of In­di­ana bi­ol­o­gist Richard Di­Marchi and se­r­i­al en­tre­pre­neur Kent Hawry­luk have launched MBX Bio­sciences, rais­ing $36.4 mil­lion in a Fra­zier Health­care Part­ners-led round to get it start­ed. For now, the pair are keep­ing their dis­eases and drug tar­gets close to the vest, say­ing on­ly that MBX will de­vel­op the same kind of mol­e­cules they de­vel­oped in pre­vi­ous com­pa­nies — large pep­tide ther­a­peu­tics — but with a fo­cus on rare en­docrine dis­or­ders, as op­posed to di­a­betes.

“There’s just a very rich his­to­ry in the field of pep­tides as mirac­u­lous med­i­cines, start­ing with in­sulin and glucagon and ex­tend­ing through a host of more re­cent reg­is­tra­tions,” Di­Marchi told End­points News. “So it is rare en­docrine dis­eases, it is large mol­e­cules, it is re­lat­ed to things I’ve done his­tor­i­cal­ly.”

The com­pa­ny is based both in the 100,000-per­son city of Carmel, In­di­ana, out­side In­di­anapo­lis, where there are 6 full-time em­ploy­ees, and at Di­Marchi’s lab in Bloom­ing­ton, where sev­er­al full-time sci­en­tists work un­der a spon­sored re­search arrange­ment. “Al­though these days, it feels like we’re based on Zoom,” Hawry­luk told End­points.

Be­fore found­ing his first biotech with Hawry­luk, Di­Marchi led the en­docrine di­vi­sion for two decades at Eli Lil­ly, where he helped de­vel­oped Hu­ma­log, Eli Lil­ly’s best-sell­ing in­sulin. In 2005, he and Hawry­luk found­ed Mar­ca­dia to de­vel­op a sol­u­ble and sta­ble ana­log for the meta­bol­ic hor­mone glucagon, a po­ten­tial treat­ment for di­a­betes and obe­si­ty. Six years lat­er, Roche snapped up the tiny biotech for $287 mil­lion in cash and up-to $250 mil­lion in mile­stones.

Roche end­ed up re­tir­ing the pro­gram short­ly there­after when they left meta­bol­ic dis­ease al­to­geth­er, Di­Marchi said, but he cred­its their work with es­tab­lish­ing the frame­work for oth­ers to en­ter the field. He specif­i­cal­ly named Zealand Phar­ma, which this year filed an NDA for dasiglucagon. He al­so named their work on a hor­mone that can hit both GIP and GLP-1 re­cep­tors, po­ten­tial­ly al­low­ing for a stronger drug for obe­si­ty, di­a­betes and NASH.

“It was our di­rec­tion that I be­lieve led oth­ers,” Di­Marchi said. “There’s prob­a­bly 2 dozen of those clin­i­cal can­di­dates cur­rent­ly be­ing ad­vanced across the globe by more than half a dozen phar­ma­ceu­ti­cal com­pa­nies.”

Lat­er, Di­Marchi and Hawry­luk launched MB2 and Cal­ib­ri­um in 2012 and 2014 to de­vel­op oth­er pro­tein-based di­a­betes drug and sold both to No­vo Nordisk in 2015 for an undis­closed sum. The progress that had been made in di­a­betes, Di­Marchi said, dic­tat­ed that they fo­cus else­where.

That work be­gan last Ju­ly, when Di­Marchi re­turned to a full time role at In­di­ana af­ter a few years work­ing part-time with No­vo Nordisk. He start­ed work­ing on syn­the­siz­ing new mol­e­cules and de­vel­op­ing in vit­ro as­says. He re­cruit­ed back Hawry­luk, who was then CBO of the RNA biotech Avid­i­ty Bio­sciences and who came over in Jan­u­ary af­ter se­cur­ing a $100 mil­lion crossover round.

There’s no time­line yet for the clin­ic or drug tar­gets. For now, Hawry­luk said, they’re look­ing for a CMO and en­joy­ing hav­ing an old band back to­geth­er.

“The jam ses­sions are a lot of fun,” he said.

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Biohaven CEO Vlad Coric (Photo Credit: Andrew Venditti)

Pssst: That big Bio­haven Alzheimer's study? It was a bust. Even the sub­group analy­sis ex­ecs tout­ed was a flop

You know it’s bad when a biopharma player plucks out a subgroup analysis for a positive take — even though it was way off the statistical mark for success, like everything else.

So it was for Biohaven $BHVN on MLK Monday, as the biotech reported on the holiday that their Phase II/III Alzheimer’s study for troriluzole flunked both co-primary endpoints as well as a key biomarker analysis.

The drug — a revised version of the ALS drug riluzole designed to regulate glutamate — did not “statistically differentiate” from placebo on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-cog) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB).  The “hippocampal volume” assessment by MRI also failed to distinguish itself from placebo for all patients fitting the mild-to-moderate disease profile they had established for the study.

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FDA hits the brakes on His­to­gen's knee car­ti­lage ther­a­py, ask­ing for more in­fo on man­u­fac­tur­ing process

A month after filing the IND application for its human extracellular matrix designed to regenerate knee cartilage, Histogen has hit a roadblock.

The FDA on Tuesday verbally notified the San Diego-based biotech that it was placing a clinical hold on the planned Phase I/II clinical trial of HST-003 due to pending CMC information and additional questions needed to complete their review.

Histogen had planned to test the safety and efficacy of implanting hECM within microfracture interstices and related cartilage defects to regenerate that cartilage in conjunction with a microfracture procedure. The company said in a press release that it expects to receive written notice of the clinical hold from the FDA by Feb 12.

Andrew Allen, Gritstone CEO (Gritstone via website)

Grit­stone con­tin­ues Covid-19 push with deal to de­vel­op 'self-am­pli­fy­ing RNA' vac­cines, as shares con­tin­ue bal­loon­ing

Gritstone Oncology has had a big week, and it’s only Wednesday.

On Tuesday, the biotech revealed plans to start clinical testing of an experimental Covid-19 vaccine — in tandem with NIAID — that can also target other coronaviruses, with the goal of preventing future pandemics should SARS-CoV-2 prove difficult to cure with current vaccines. Then, on Wednesday morning, Gritstone licensed lipid nanoparticle technology from Genevant Sciences to develop what it’s calling “self-amplifying RNA vaccines” against Covid-19.

Hal Barron, GSK R&D chief (GSK via YouTube)

Glax­o­SmithK­line's $4B bis­pe­cif­ic can­cer drug al­liance with Mer­ck KGaA hit by big set­back with a PhI­II fail­ure on NSCLC

Close to 2 years ago, GSK’s R&D team eagerly agreed to pay up to $4 billion-plus to ally itself with Merck KGaA on a mid-stage bispecific called bintrafusp alfa, which intrigued them with the combination of a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein.

But today the German pharma company says that their lead study on lung cancer was a bust, as independent monitors said there was no reason to believe that the experimental drug — targeting PD-L1/TGF-Beta — could beat Keytruda.

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The IPO flood keeps ris­ing with 4 more biotechs and a SPAC on their way to Nas­daq

After a record year for biotech IPOs in 2020, forecasts were bullish on another strong year showing for public offerings — and 2021 hasn’t disappointed so far. Now, a clutch of four biotechs chasing rare disease and cancer and a New York SPAC are ready to join the party.

Three more companies filed to head to Nasdaq on Tuesday, as well as a SPAC, with an additional Dutch biotech filing Friday. All in all, early days indicate another big year, at least to start, with 12 companies either pricing or filing their IPOs in the first 20 days of January.

Janet Woodcock and Joshua Sharfstein (AP, Images)

Poll: Should Joshua Sharf­stein or Janet Wood­cock lead the FDA from here?

It’s time for a new FDA commissioner to come on board, a rite of passage for Joe Biden’s administration that should help seal the new president’s rep on seeking out the experts to lead the government over the next 4 years.

As of now, the competition for the top job appears to have narrowed down to 2 people: The longtime CDER chief Janet Woodcock and Joshua Sharfstein, the former principal deputy at the FDA under Peggy Hamburg. Both were appointed by Barack Obama.

Bris­tol My­ers Squibb gets re­view date for Op­di­vo com­bo in gas­tric can­cer, look­ing to over­turn Keytru­da's 3-year lead

The past two months have been tough for Bristol Myers Squibb and its checkpoint inhibitor Opdivo after setbacks in lung and brain cancers. But in the battle against Merck’s Keytruda, any success matters — and now Bristol could be looking at a quick approval for Opdivo in an unmatched indication.

The FDA will launch a speedy review of a combination of Bristol Myers Squibb’s Opdivo and chemotherapy to treat first-line patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma, the drugmaker said Wednesday. The agency set an action date of May 25 for the application.

Covid-19 claims an­oth­er PDU­FA vic­tim as Glax­o­SmithK­line push­es back planned PD-1 roll­out

Bristol Myers Squibb isn’t the only pharma giant that’s been standing in the FDA’s waiting line for site inspections.

GlaxoSmithKline is telling us today that their H2 2020 PDUFA deadline for the PD-1 drug dostarlimab — picked up in its Tesaro buyout — was pushed back due to a delay in the manufacturing site inspection needed for a regulatory decision. And that is forcing the company to revise its timeline.

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