Al­lievex launch­es with Pap­pas cash and rare dis­ease drug from Bio­Marin

In Ju­ly 2015, Bio­Marin be­gan a se­ries of tri­als for a drug tar­get­ing a rare and fa­tal child­hood dis­ease that had re­mained vir­tu­al­ly un­changed since its 1963 dis­cov­ery. Now, with their lead can­di­date en­ter­ing Phase II, they’re hand­ing it off to a new com­pa­ny out of Pap­pas Cap­i­tal: Al­lievex.

Backed by Pap­pas and No­vo Hold­ings, Al­lievex will tack­le San­fil­ip­po Syn­drome type B, a lyso­so­mal neu­ro­log­i­cal con­di­tion for which no treat­ment ex­ists. Al­lievex CEO Thomas Math­ers in­di­cat­ed to End­points News that the new com­pa­ny would broad­ly fo­cus on child­hood con­di­tions but be­gin with San­fil­ip­po and the Bio­Marin treat­ment:

Thomas Math­ers

“Tralesinidase al­fa may be the first dis­ease mod­i­fy­ing ther­a­py which could pro­vide cog­ni­tive sta­bi­liza­tion or growth, as well as po­ten­tial­ly im­pact hear­ing, sleep, bow­el habits and over­all qual­i­ty of life for San­fil­ip­po B chil­dren,” Math­ers wrote Endpts in an email. “The FDA re­cent­ly is­sued a draft guid­ance for in­dus­try which we be­lieve di­rect­ly speaks to San­fil­ip­po B, and we be­lieve that this Guid­ance pro­vides Al­lievex a clear road map to reg­is­ter tralesinidase al­fa.”

Al­lievex and its part­ners, though, have not dis­closed how much fund­ing they’re get­ting. The FDA guid­ance is a Ju­ly 2018 doc­u­ment de­tail­ing ev­i­dence stan­dards for drugs aimed at en­zyme-based, rare, slow-pro­gress­ing dis­eases.

Tralesinidase al­fa is a form of en­zyme re­place­ment ther­a­py, a type of treat­ment used pri­mar­i­ly in oth­er lyso­so­mal dis­eases — dis­eases that arise from dis­abling mu­ta­tions in the en­zyme-con­tain­ing sacs found in­side cells. In San­fil­ip­po, the cells can’t de­grade a sug­ar called he­paran sul­fate, which ac­cu­mu­lates and even­tu­al­ly kills neu­rons and oth­er or­gan cells.

The slow buildup gives the dis­ease a par­tic­u­lar­ly ag­o­niz­ing arc: healthy de­vel­op­ment in­to around age two, when cog­ni­tive skills and sen­so­ry func­tion can be­gin to de­cline rapid­ly. Most die in their teens. The sec­ond most com­mon form of the dis­ease, San­fil­ip­po B, af­fects about 1 in every 200,000 peo­ple.

In the ther­a­py, sci­en­tists cre­ate a re­com­bi­nant form of the miss­ing en­zyme — al­pha-N-acetyl­glu­cosaminidase or NAGLU — and in­ject it di­rect­ly in­to brain ven­tri­cles through a spe­cial­ized catheter, ide­al­ly de­grad­ing the he­paran sul­fate and stem­ming the degra­da­tion of cells. The en­zymes have to be in­ject­ed in­to the brain be­cause oth­er­wise, they will not cross the blood-brain bar­ri­er.

Bio­Marin has com­plet­ed an ob­ser­va­tion­al study and re­cent­ly be­gan a Phase II study.

Al­lievex won’t be the first com­pa­ny to try en­zyme ther­a­py on San­fil­ip­po B. Alex­ion spent $8.4 bil­lion to ac­quire Synage­va in 2015, pri­mar­i­ly to ac­quire Kanu­ma but in part for SBC-103, a re­com­bi­nant form of NAGLU. They saw some ear­ly pos­i­tive re­sults but shelved the drug in 2017.

A 2015 re­view of the dis­ease in Dove Med­ical Press, not­ed that in an­i­mals — the Bio­Marin Phase I/II clin­i­cal tri­als had yet to be­gin — en­zyme in­jec­tion in­to the brain “has been suc­cess­ful in al­le­vi­at­ing a num­ber of symp­toms but has al­so em­pha­sized the im­por­tance of ear­ly de­tec­tion on ac­count of the ir­re­versibil­i­ty of cer­tain (par­tic­u­lar­ly neu­rode­gen­er­a­tive) as­pects of the patho­phys­i­ol­o­gy.”

Abeona is al­so work­ing on a form of gene ther­a­py for San­fil­ip­po A, now in Phase I/II, but that has lim­it­ed im­pli­ca­tions for oth­er forms of the dis­ease. Al­though San­fil­ip­po A, B, C, and D man­i­fest in sim­i­lar ways, they dif­fer in their ge­net­ic foun­da­tions.

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

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The lat­est Cin­derel­la sto­ry in on­col­o­gy ends with a sud­den rout as up­dat­ed da­ta dis­play spooks in­vestors

NextCure’s turn as the Cinderella of cancer-focused biotechs was short-lived.
Just a few days after its shares $NXTC zoomed up more than 250% on some very early stage results in a SITC abstract, a more complete analysis over the weekend spiked the hype and left investors in high dudgeon as the stock price collapsed back towards earth Monday.
The focus at NextCure is centered on NC318, an antibody that is intended to shut down the immunosuppressive Siglec-15 — or S-15 — target. After adding a small group of patients to the readout, investigators circled 2 clinical responses, a complete and partial response, along with 4 stable disease cases in non-small cell lung cancer.

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Te­va spin­out rais­es $85M in IPO; No­var­tis beefs up gener­ics unit with $440M deal

→ After Teva spinout 89bio recently announced that its IPO was being held up, the company is back in the game offering 5,304,687 shares at a price of $16 per share. The company has raised $84.9 million IPO in gross proceeds and will be listed under the ticker symbol $ETNB. BofA Securities, SVB Leerink and RBC Capital Markets are the joint book-running managers for the offering. Oppenheimer & Co is the co-manager for the offering.
→ Looking to amp up its presence in Japan’s hospitals, Novartis has struck a deal to buy out Aspen’s portfolio of generics in the world’s third largest healthcare market. The pharma giant is paying $440 million for Aspen’s Japanese subsidiary.
→ Novartis said tropifexor, a non-bile acid FXR agonist, has scored on several key biomarkers of NASH in a Phase IIb trial, including reductions in hepatic fat, alanine aminotransferase and body weight compared to a placebo at 12 weeks.

Break­through sta­tus and promise of a speedy re­view ar­rives for Op­di­vo/Yer­voy com­bi­na­tion as Bris­tol-My­ers bites at Bay­er

Its frontline and single-agent aspirations have been set back, but Bristol-Myers Squibb just took a big step forward in its efforts to apply its checkpoint inhibitor Opdivo to liver cancer. The FDA has granted breakthrough status and priority review to a combination, second-line treatment.

The designation is for Opdivo (nivolumab) in combination with Yervoy (ipilimumab),  for treating advanced hepatocellular carcinoma (HCC), the most common form of liver cancer. The PD-L1 drug was already approved as a single-agent, second-line treatment for HCC. A PDUFA date was set for March 10, 2020 — just 4 months from now.

Third time un­lucky: Lipocine's lat­est quest to mar­ket their oral testos­terone drug snubbed again by FDA

Lipocine’s latest attempt at securing approval for its oral testosterone drug has fizzled yet again.

The Utah-based drug developer on Monday said the FDA has spurned its marketing application, indicating that some efficacy data on the drug, Tlando, was not up to scratch to treat male hypogonadism, a condition characterized by low production of the hormone testosterone, which is responsible for maintaining muscle bulk, bone growth, and sexual function.

UP­DAT­ED: De­cry­ing 'ar­bi­trary and capri­cious' ac­tion, Re­genxBio sues FDA over clin­i­cal holds on gene ther­a­py

When RegenxBio disclosed that the FDA had placed a partial clinical hold on one of its lead gene therapies, execs outlined several customary next steps: continuing assessment and monitoring, delaying a related IND filing, and working with the FDA to address the matter.

As it turned out, they were planning something much less mundane. Two days after announcing the hold in its Q3 update, RegenxBio filed a lawsuit seeking to set it aside, the FDA Law Blog noted.

Roche's SMA chal­lenge to Bio­gen's Spin­raza fran­chise looms larg­er with piv­otal win

Roche has just landed a crucial advance in scoring a come-from-behind win on the spinal muscular atrophy field, giving Novartis and Biogen a run for their money.

The update was brief, but Roche said risdiplam hit the primary endpoint in the placebo-controlled pivotal SUNFISH trial, meeting the threshold for change from baseline in the Motor Function Measure 32 (MFM-32) scale after one year of treatment. The results, which is the second, confirmatory portion of a two-part study, involved 180 patients with type 2 or 3 spinal muscular atrophy between 2 and 25 years old.

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Roche steers Gazy­va in­to a new PhI­II pro­gram af­ter com­bo shows promise in lu­pus nephri­tis study

Roche is working on putting together a late-stage study for its monoclonal antibody Gazyva in patients with severe kidney disease associated with lupus after a combination approach helped patients in a mid-stage study.

The 125-patient NOBILITY trial evaluated Gazyva, combined with standard-of-care treatment mycophenolate mofetil or mycophenolic acid and corticosteroids, versus standard treatment alone. The combo met the main goal of inducing a statistically superior complete renal response (CRR) of 40% at week 76, versus 18% in patients given standard treatment, Roche said.