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 Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data is messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data is exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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David Lockhart, ReCode Therapeutics CEO

Pfiz­er throws its weight be­hind LNP play­er eye­ing mR­NA treat­ments for CF, PCD

David Lockhart did not see the meteoric rise of messenger RNA and lipid nanoparticles coming.

Thanks to the worldwide fight against Covid-19, mRNA — the genetic code that can be engineered to turn the body into a mini protein factory — and LNPs, those tiny bubbles of fat carrying those instructions, have found their way into hundreds of millions of people. Within the biotech world, pioneers like Alnylam and Intellia have demonstrated just how versatile LNPs can be as a delivery vehicle for anything from siRNA to CRISPR/Cas9.

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No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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Pascal Soriot, AstraZeneca CEO (via Getty images)

UP­DAT­ED: FDA slaps As­traZeneca's MCL-1 can­cer drug with a hold af­ter safe­ty is­sue — 2 years af­ter Am­gen axed a trou­bled ri­val

There are new questions being posed about a class of cancer drugs in the wake of the second FDA-enforced clinical hold in the field.

Two years after the FDA hit Amgen with a clinical hold on its MCL-1 inhibitor AMG 397 following signs of cardiac toxicity, AstraZeneca says that regulators hit them with a hold on their rival therapy of the same class.

The pharma giant noted on clinicaltrials.gov that its Phase I/II study for the MCL-1 drug AZD5991 “has been put on hold to allow further evaluation of safety related information.”

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Sur­geons suc­cess­ful­ly at­tach pig kid­ney to a hu­man for the first time, us­ing tech from Unit­ed's Re­vivi­cor

In a first, researchers reportedly successfully transplanted a pig kidney into a human without triggering an immediate immune response this week. And the technology came from the biotech United Therapeutics.

Surgeons spent three days attaching the kidney to the patient’s blood vessels, but when all was said and done, the kidney appeared to be functioning normally in early testing, Reuters and the New York Times were among those to report. The kidney came from a genetically altered pig developed through United’s Revivicor unit.

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Leen Kawas (L) has resigned as CEO of Athira and will be replaced by COO Mark Litton

Ex­clu­sive: Athi­ra CEO Leen Kawas re­signs af­ter in­ves­ti­ga­tion finds she ma­nip­u­lat­ed da­ta

Leen Kawas, CEO and founder of the Alzheimer’s upstart Athira Pharma, has resigned after an internal investigation found she altered images in her doctoral thesis and four other papers that were foundational to establishing the company.

Mark Litton, the company’s COO since June 2019 and a longtime biotech executive, has been named full-time CEO. Kawas, meanwhile, will no longer have ties to the company except for owning a few hundred thousand shares.

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Sen. Richard Durbin (D-IL, foreground) and Sen. Richard Blumenthal (D-CT) (Patrick Semansky/AP Images)

Sen­a­tors back FDA's plan to re­quire manda­to­ry pre­scriber ed­u­ca­tion for opi­oids

Three Senate Democrats are backing an FDA plan to require mandatory prescriber education for opioids as overdose deaths have risen sharply over the past decade, with almost 97,000 American opioid-related overdose deaths in the past year alone.

While acknowledging a decline in overall opioid analgesic dispensing in recent years, the FDA said it’s reconsidering the need for mandatory prescriber training through a REMS given the current situation with overdoses, and is seeking input on the aspects of the opioid crisis that mandatory training could potentially mitigate.

Bris­tol My­ers pledges to sell its Ac­celeron shares as ac­tivist in­vestors cir­cle Mer­ck­'s $11.5B buy­out — re­port

Just as Avoro Capital’s campaign to derail Merck’s proposed $11.5 billion buyout of Acceleron gains steam, Bristol Myers Squibb is leaning in with some hefty counterweight.

The pharma giant is planning to tender its Acceleron shares, Bloomberg reported, which add up to a sizable 11.5% stake. Based on the offer price, the sale would net Bristol Myers around $1.3 billion.

To complete its deal, Merck needs a majority of shareholders to agree to sell their shares.