Bryan Stuart (Fulcrum)

Aim­ing to brush last year's flop aside, Ful­crum sees shares sky­rock­et on ear­ly look at sick­le cell pro­gram

Ful­crum Ther­a­peu­tics $FULC is look­ing to re­bound af­ter the Phase II flop of an old Glax­o­SmithK­line drug slashed their mar­ket val­ue in half last Au­gust. And if Tues­day’s stock move­ment is any in­di­ca­tion, in­vestors like what they see.

At an in­ter­im analy­sis of a Phase I study, Ful­crum re­port­ed that their pro­gram de­signed to treat in­her­it­ed blood dis­or­ders hit a sta­tis­ti­cal­ly sig­nif­i­cant rate in two key mea­sure­ments, the com­pa­ny an­nounced Tues­day morn­ing. The re­sults sent Ful­crum shares sky­rock­et­ing more than 125%, send­ing the stock price back above what it had been be­fore last year’s whiff.

The pro­gram, known as FTX-6058, is be­ing de­vel­oped for sick­le cell dis­ease and non-sick­le cell he­mo­glo­binopathies, such as be­ta tha­lassemia.

Tues­day’s re­sults come from a ran­dom­ized and dou­ble-blind­ed study look­ing at healthy vol­un­teers over the course of 14 days. Ful­crum ran both sin­gle-as­cend­ing dose and mul­ti­ple-as­cend­ing dose por­tions of the tri­al, with Tues­day’s da­ta com­ing from the lat­ter where in­di­vid­u­als re­ceived ei­ther 2 mg, 6 mg or 10 mg dos­es dai­ly.

Across the co­horts, re­searchers saw dose pro­por­tion­al in­duc­tions in HBG mR­NA and ac­com­pa­ny­ing in­creas­es in F-retic­u­lo­cytes, two mark­ers on which in­vestors keyed in. The 10 mg dose in par­tic­u­lar proved pos­i­tive, Ful­crum not­ed, with FTX-6058 reach­ing mean changes of 4.5-fold and 4.2-fold in each mea­sure, re­spec­tive­ly.

The pro­gram hit the 4.5-fold in­crease for HBG mR­NA mean fold in­duc­tion at the 14-day mark, while notch­ing the 4.2-fold in­crease in F-retic­u­lo­cytes at the 21-to-24-day safe­ty fol­low-up. Both as­sess­ments hit p-val­ues of p<0.0001.

“Pre­clin­i­cal­ly, we demon­strat­ed con­sis­tent 2-3-fold in­duc­tion of HBG mR­NA and HbF pro­tein both in vit­ro and in vi­vo,” CEO Bryan Stu­art said in a state­ment. He con­tin­ued that the clin­i­cal re­sults “demon­strate the first ev­i­dence that FTX-6058 can achieve or ex­ceed these pre­clin­i­cal thresh­olds pre­dict­ed to pro­vide mean­ing­ful clin­i­cal ben­e­fits to in­di­vid­u­als with SCD.”

An­a­lysts were sur­prised but pleased with the in­creas­es, with Stifel’s Dae Gon Ha not­ing any HBG mR­NA in­duc­tion would have been seen as a pos­i­tive. Ha high­light­ed, how­ev­er, the small tri­al pop­u­la­tion, the short du­ra­tion and the fact that par­tic­i­pants did not have sick­le cell dis­ease are “key caveats” to the safe­ty as­pect of Tues­day’s re­sults.

Ful­crum re­port­ed few tri­al dis­con­tin­u­a­tions and on­ly one se­ri­ous side ef­fect at Grade 4, an asymp­to­matic in­crease in cre­a­tine phos­pho­k­i­nase at the 10 mg dose.

“As an epi­ge­net­ic-tar­get­ing drug that like­ly re­quires chron­ic dos­ing in pa­tients, at this time we can­not rule out po­ten­tial safe­ty/tol­er­a­bil­i­ty sig­nals up­on ex­tend­ed pe­ri­od of dos­ing,” Ha wrote to in­vestors. “Thus, while we are en­cour­aged by the safe­ty progress to-date in this 14-day study, we an­tic­i­pate a more com­pre­hen­sive safe­ty overview to emerge from sub­se­quent tri­als.”

Look­ing ahead, Ful­crum plans to launch a Phase Ib study in sick­le cell pa­tients in the fourth quar­ter, which will dose par­tic­i­pants over three months. Both Ha and SVB Leerink’s Joseph Schwartz wrote they’ll be keep­ing an eye on how the longer treat­ment pe­ri­od af­fects the two mea­sure­ments re­port­ed Tues­day, as well as the dura­bil­i­ty of treat­ment ef­fect.

Ful­crum al­so ex­pects to sub­mit an IND in non-SCD he­mo­glo­binopathies by the end of 2021.

Tues­day’s news comes al­most a year to the day af­ter Ful­crum took a nose­dive off a Phase II fail of the old GSK drug losmapi­mod. Re­searchers had been look­ing at whether the p38α/β MAPK in­hibitor could sig­nif­i­cant­ly re­duce a cer­tain gene’s ex­pres­sion in fa­cioscapu­lo­humer­al mus­cu­lar dy­s­tro­phy af­ter 16 weeks.

Biotech in­vestors and CEOs see two paths to growth, but are they equal­ly vi­able?

The dynamic in the biotech market has been highly volatile in the last few years, from the high peaks immediately after the COVID vaccine in 2021, to the lowest downturns of the last 20 years in 2022. This uncertainty makes calling the exact timing of the market’s turn something of a fool’s errand, according to Dr. Chen Yu, Founder and Managing Partner of TCG Crossover (TCG X). He speaks with RBC’s Noël Brown, Head of US Biotechnology Investment Banking, about the market’s road ahead and two possible paths for growth.

Casey McPherson shows his daughters Rose (left) and Weston around Everlum Bio, a lab that he co-founded to spark a treatment for Rose and others with ultra-rare conditions. (Ilana Panich-Linsman)

Fa­ther starts lab af­ter in­tel­lec­tu­al prop­er­ty is­sues stymie rare dis­ease drug de­vel­op­ment

Under bright lab lights, Casey McPherson holds his 6-year-old daughter, Rose. His free hand directs Rose’s gaze toward a computer screen with potential clues in treating her one-of-a kind genetic condition.

Gray specks on the screen show her cells that scientists reprogrammed with the goal of zeroing in on a custom medicine. McPherson co-founded the lab, Everlum Bio, to spark a treatment for Rose — and others like her. A regarded singer-songwriter, McPherson never imagined going into drug development.

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Fireside chat between Hal Barron and John Carroll, UKBIO19

It’s time we talked about bio­phar­ma — live in Lon­don next week

Zoom can only go so far. And I think at this stage, we’ve all tested the limits of staying in touch — virtually. So I’m particularly happy now that we’ve revved up the travel machine to point myself to London for the first time in several years.

Whatever events we have lined up, we’ve always built in plenty of opportunities for all of us to get together and talk. For London, live, I plan to be right out front, meeting with and chatting with the small crowd of biopharma people we are hosting on October 12 at Silicon Valley Bank’s London headquarters. And there’s a lengthy mixer at the end I’m most looking forward to, with several networking openings between sessions.

Take­da to pull key hy­poparathy­roidism drug from the mar­ket af­ter years of man­u­fac­tur­ing woes

Takeda on Tuesday morning made an announcement that almost 3,000 people with the rare disease known as hypoparathyroidism were fearing.

Due to unresolved supply issues and manufacturing woes, Takeda said it will cut its losses and discontinue its hypoparathyroidism drug, known as Natpara (parathyroid hormone), halting all manufacturing of the drug by the end of 2024, but the entire inventory will be available until depleted or expired, a company spokesperson said via email.

Pfizer and BioNTech's original Marvel comic book links evolving Covid vaccine science to Avengers' evolving villain-fighting tools.(Source: Pfizer LinkedIn post)

Pfiz­er, BioN­Tech part­ner with Mar­vel for Avengers and Covid-fight­ing com­ic book

Pfizer and BioNTech are collaborating with Marvel to celebrate “everyday” people getting Covid-19 vaccines in a custom comic book.

In the “Everyday Heroes” digital comic book, an evolving Ultron, one of the Avengers’ leading villains, is defeated by Captain America, Ironman and others. The plotline and history of Ultron is explained by a grandfather who is waiting with his family at a clinic for Covid-19 vaccinations.

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Kaile Zagger, Infinant Health CEO

UC Davis mi­cro­bio­me spin­out re­brands in­fant sup­ple­ment busi­ness with na­ture fo­cus

When Kaile Zagger took the helm of UC Davis spinout Evolve Biosystems several months ago, the company billed itself as a probiotic maker.

However, she believes the company’s Evivo supplement designed to help infants develop a healthy gut microbiome is “so much more” — and that, she said, calls for a rebrand.

Evolve has, well, evolved into Infinant Health, the company announced on Monday. The new name is a mash-up of the words “infant” and “infinite,” representing the company’s goal of expanding beyond infant care. While its sole product, Evivo, is intended for newborns, Infinant is “quickly developing” an option for kids through the age of two.

FDA+ roundup: Ad­comm date set for Cy­to­ki­net­ics heart drug; New gener­ic drug guid­ance to re­duce fa­cil­i­ty de­lays

The FDA has set Dec. 13 as the day that its Cardiovascular and Renal Drugs Advisory Committee will review Cytokinetics’ potential heart drug, setting up a key vote ahead of a Feb. 28, 2023 PDUFA date.

The drug, known as omecamtiv mecarbil, read out its first Phase III in November 2020, hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as the key to breaking into the market, failing to significantly differ in reducing cardiovascular death from placebo.

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Bob Azelby, Eliem Therapeutics CEO

Eliem says ear­li­er drug ex­po­sure is­sues have been re­solved, drops one epilep­sy in­di­ca­tion

After being forced to delay two Phase IIa trials and blaming CMC issues on a Phase Ib miss, Eliem Therapeutics believes it’s now in the clear.

The Seattle and UK-based biotech put out word Wednesday morning about how it conducted new early-stage studies to confirm why low exposure issues arose during the Phase Ib. After researchers compared the results of the studies, Eliem found “no meaningful difference” between them and ruled out CMC as the reason for the foiled Phase Ib study, the company said in a press release.

GSK touts topline win for PD-1 in head-to-head with Keytru­da — while steer­ing next big check­point drug in­to PhI­II

GSK is claiming a win for what it calls the largest head-to-head trial pitting a PD-1 against Merck’s best-selling Keytruda in a type of lung cancer, as its Jemperli met the primary endpoint of objective response rate.

In a separate positive move, GSK says it’s moving both arms of the COSTAR Lung trial into Phase III to test Jemperli as well as the TIM-3 inhibitor cobolimab.

Hesham Abdullah, GSK’s global head of oncology development, said in a statement that the two trials “support the ambition for dostarlimab to become the backbone of our ongoing immuno-oncology-based research and development programme when used alone and in combination with standard of care and future novel cancer therapies, particularly in patients with currently limited treatment options.”

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