Alex­ion lines up a $60M op­tion to buy Fortress-in­cu­bat­ed biotech fo­cused on a lu­cra­tive rare blood dis­ease

Now that Alex­ion has se­cured an FDA ap­proval for Ul­tomiris, the fol­low-on for its flag­ship drug Soliris, the biotech is back on the hunt for po­ten­tial ad­di­tions to its rare blood dis­or­der port­fo­lio.

One of them will be a tar­get­ed ther­a­py for light chain amy­loi­do­sis, which Alex­ion has las­soed with a buy­out op­tion in its col­lab­o­ra­tion deal with Caelum Bio­sciences. Alex­ion is hand­ing over $60 mil­lion for a mi­nor­i­ty stake and an ex­clu­sive op­tion to ac­quire the rest — a de­ci­sion they will make when the Phase II da­ta are ripe for re­view.

John Orloff

Start­up in­cu­ba­tor Fortress Biotech launched Caelum in 2017 af­ter li­cens­ing the an­ti-amy­loid an­ti­body they now call CAEL-101 from Co­lum­bia based on re­search by Alan Solomon of the Uni­ver­si­ty of Ten­nessee Grad­u­ate School of Med­i­cine. Break­ing from the old ap­proach, which fo­cus­es on block­ing pro­duc­tion of new amy­loids, he de­signed the ther­a­py to break up pre-ex­ist­ing amy­loid de­posits clog­ging up in tis­sues to dam­age pa­tients’ or­gans, par­tic­u­lar hearts and kid­neys.

“CAEL-101 ap­pears to have a unique ca­pa­bil­i­ty of bind­ing to both kap­pa and lamb­da mis­fold­ed pro­teins,” Caelum CEO Michael Spec­tor said in a state­ment. “Da­ta from the Phase 1a/1b study in­di­cate that CAEL-101 is a well-tol­er­at­ed ther­a­py that leads to a rapid and clin­i­cal­ly rel­e­vant or­gan re­sponse, par­tic­u­lar­ly in the heart and kid­neys. Fur­ther, CAEL-101 showed a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment from base­line in glob­al lon­gi­tu­di­nal strain, an end­point that has been cor­re­lat­ed with sur­vival in pa­tients with AL amy­loi­do­sis.”

For Alex­ion, this will be an op­por­tu­ni­ty to tap in­to a fa­tal dis­ease with no ap­proved ther­a­pies, R&D chief John Orloff said. Prothena took a stab at it but late-stage fail­ures forced it to scrap its en­tire lead pro­gram.

Michael Spec­tor

Whether Prothena’s fail­ure had to do with its drug (as Alex­ion be­lieves) or the en­tire hy­poth­e­sis about tar­get­ing AL amy­loid is to be borne out, Stifel an­a­lysts wrote in a note, mak­ing this a cheap bet with not just high po­ten­tial re­ward but al­so “fair­ly high risk.”

“Alex­ion’s ar­gu­ment here is that CAEL-101 ben­e­fits from a much stronger mech­a­nis­tic ra­tio­nale, though NEOD001 pre­clin­i­cal da­ta paint a dif­fer­ent pic­ture,” they wrote. “In a pre­sen­ta­tion at the 2018 In­ter­na­tion­al Sym­po­sium on Amy­loi­do­sis, a pre­clin­i­cal poster sug­gest­ed that NEOD001 binds an epi­tope on kap­pa and lam­da light-chain pro­teins that in their view is “unique­ly ex­posed dur­ing mis­fold­ing and ag­gre­ga­tion”. It’s plau­si­ble (but how would we know) that this was not re­ca­pit­u­lat­ed in pa­tients.”

Alex­ion will now play a part in shap­ing the Phase II pro­gram for CAEL-101 as Caelum re­mains re­spon­si­ble for the ex­e­cu­tion and man­u­fac­tur­ing. If the da­ta hold up, the buy­out deal will amount to as much as $500 mil­lion.

The deal adds to a steady stream of ear­ly-stage as­sets Alex­ion has been bring­ing in­to its pipeline, in­clud­ing a pre­clin­i­cal C6 com­ple­ment in­hibitor from an­oth­er op­tion deal with Com­ple­ment Phar­ma and a (much more ex­pen­sive) drug for rare IgG-me­di­at­ed dis­eases, which it bagged when ac­quir­ing Syn­tim­mune for $400 mil­lion up­front.

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.

NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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Marty Duvall, Oncopeptides CEO

On­copep­tides stock craters as it pulls can­cer drug Pepax­to from the mar­ket

Shares of Oncopeptides crashed more than 70% in early Friday trading after the company said it’s pulling its multiple myeloma drug Pepaxto (melphalan flufenamide) from the US market after failing a confirmatory trial. The move will force the company to close its US and EU business units and enact significant layoffs.

The FDA had scheduled an adcomm meeting next Thursday to discuss Pepaxto, which first won accelerated approval in February and costs about $19,000 per course of treatment. The committee was to weigh in on whether the confirmatory trial demonstrated a worse overall survival in the treatment arm compared to the control arm.

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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 are 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 are 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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Pfiz­er pitch­es its Covid-19 vac­cine for younger chil­dren ahead of ad­comm next week

Pfizer will present its case to the FDA’s vaccine adcomm next week, seeking authorization for a lower-dose version of its Covid-19 vaccine for kids ages 5 through 12, which the Biden administration said will likely begin rolling out early next month.

Two primary doses of the 10 µg vaccine (the dose for those ages 12 and up is 30 μg) given 3 weeks apart in this group of children “have shown a favorable safety and tolerability profile, robust immune responses against all variants of concern including Delta, and vaccine efficacy of 90.7% against laboratory-confirmed symptomatic COVID-19,” the company said in briefing documents ahead of next Tuesday’s meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.

Jay Flatley, new Zymergen CEO

Fol­low­ing Au­gust melt­down, Zymer­gen hints at sal­vage plans — cut­ting jobs and rene­go­ti­at­ing loans

Two months after a spectacular implosion that saw its founding CEO leave his post amid customer reports its only product didn’t work, Zymergen provided the first peek behind the curtain for its plans moving forward.

In an SEC filing Wednesday, Zymergen told regulators it would slash about 100 jobs and had renegotiated a $100 million loan from Perceptive that loomed like a storm cloud over the company, moving up the maturity date 18 months to June 30, 2022. Jed Dean, one of Zymergen’s three co-founders and VP of operations, will also step down at the end of the month.

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Sanofi, Re­gen­eron etch out an­oth­er PhI­II vic­to­ry for Dupix­ent, eas­ing se­vere itch and clear­ing le­sions

Sanofi and Regeneron can boast of another inflammatory disease where Dupixent has proven effective.

The best-selling drug, which targets both IL-4 and IL-13, has delivered a clean sweep in a Phase III trial for prurigo nodularis, a chronic disease characterized by itch so intense that it can affect patients’ sleep and psychology. Thick skin lesions can cover most of the body.

On the primary endpoint, 37% of patients taking Dupixent saw a clinically meaningful reduction in itch compared to 22% of those on placebo (p=0.0216) at week 12. All secondary endpoints were also met, including clearance of skin lesions and improvement in quality of life.

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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