John McHutchison, Assembly Biosciences CEO (Getty Images)

As­sem­bly Bio's he­pati­tis B pro­gram flops as a po­ten­tial cure in PhII, send­ing shares spi­ral­ing

Look­ing for a he­pati­tis B cure, As­sem­bly Bio­sciences $ASMB has struck out in a Phase II.

The South San Fran­cis­co-based com­pa­ny an­nounced Thurs­day af­ter­noon that its lead ex­per­i­men­tal drug ve­bi­corvir, in com­bi­na­tion with nu­cle­o­side ther­a­py, could not keep pa­tients dis­ease-free af­ter stop­ping treat­ments. In to­tal, 39 of the 41 in­di­vid­u­als in the open-la­bel study re­lapsed, as the reg­i­men failed to achieve a mean­ing­ful sus­tained vi­ro­log­ic re­sponse.

In­vestors did not take too kind­ly to the news, ham­mer­ing the biotech’s share prices af­ter the bell. As­sem­bly’s stock dropped as much as 40% on Thurs­day evening but has since lev­eled off to down about 35%.

The He­pati­tis B pa­tients in­volved in As­sem­bly’s Phase II gen­er­al­ly re­quire treat­ments for the rest of their lives. As­sem­bly’s the­o­ry went that if they could show enough of a pro­longed re­sponse af­ter tak­ing pa­tients off the pro­gram, which is sep­a­rate­ly be­ing stud­ied as a chron­ic sup­pres­sive ther­a­py, then it could ef­fec­tive­ly func­tion as a cure.

In or­der to find that out, As­sem­bly treat­ed their pa­tients with the com­bi­na­tion ther­a­py for 12 to 18 months. Fol­low­ing that pe­ri­od, re­searchers stopped the treat­ments and eval­u­at­ed the 41 pa­tients every four weeks to see whether or not the com­bo was ef­fec­tive enough at pre­vent­ing a re­lapse af­ter an ex­tend­ed pe­ri­od of time.

But 33 of the 41 pa­tients saw their he­pati­tis B re­turn af­ter the first four-week eval­u­a­tion. By the 16-week mark, an­oth­er six pa­tients re­lapsed. As­sem­bly had been look­ing for an SVR rate of at least 15% af­ter 24 weeks, but Thurs­day’s re­sults equate to a rate of less than 5%.

Though Thurs­day’s re­sults are in­deed a neg­a­tive, As­sem­bly’s com­bo still has po­ten­tial as a chron­ic ther­a­py, Baird’s Bri­an Sko­r­ney wrote in a note to in­vestors. See­ing that the near-term cure play is now “off the ta­ble,” Sko­r­ney says As­sem­bly can ef­fec­tive­ly piv­ot to­ward that path, but notes the up­side is much more lim­it­ed.

“Al­though the busi­ness op­por­tu­ni­ty for a chron­ic ther­a­py for He­pati­tis B is much less at­trac­tive than a cu­ra­tive reg­i­men, we still see it as a rea­son­able busi­ness,” Sko­r­ney wrote.

Should As­sem­bly take that route, Sko­r­ney pre­dicts the ther­a­py could reach any­where be­tween $500 mil­lion and $1 bil­lion in an­nu­al sales.

As­sem­bly has pre­vi­ous­ly tak­en steps to turn that in­to a re­al­i­ty, ink­ing a $540 mil­lion deal with BeiGene in Ju­ly to take the ve­bi­corvir and nu­cle­o­side com­bo in­to a Phase III for chron­ic sup­pres­sion of He­pati­tis B. The tri­al is ex­pect­ed to be­gin some­time in the first half of next year, and will in­clude a group of pa­tients who have seen on­ly par­tial vi­ral sup­pres­sion af­ter a year or more of nu­cle­o­side monother­a­py.

The com­pa­ny is al­so look­ing in­to whether ve­bi­corvir could still cure he­pati­tis B in a triple ther­a­py con­coc­tion. In Au­gust, As­sem­bly hooked on­to a deal with Ar­bu­tus Bio­phar­ma and plans to launch the first Phase II next year that com­bines ve­bi­corvir, nu­cle­o­side treat­ment and Ar­bu­tus’ RNAi ther­a­peu­tic for the dis­ease. Sko­r­ney notes the com­pa­nies are still in the ear­ly de­vel­op­men­tal stages, how­ev­er.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.

Jay Bradner (Jeff Rumans for Endpoints News)

Div­ing deep­er in­to in­her­it­ed reti­nal dis­or­ders, No­var­tis gob­bles up an­oth­er bite-sized op­to­ge­net­ics biotech

Right about a year ago, a Novartis team led by Jay Bradner and Cynthia Grosskreutz at NIBR swooped in to scoop up a Cambridge, MA-based opthalmology gene therapy company called Vedere. Their focus was on a rather narrow market niche: inherited retinal dystrophies that include a wide range of genetic retinal disorders marked by the loss of photoreceptor cells and progressive vision loss.

But that was just the first deal that whet their appetite.

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FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

Mi­rati's KRAS drug looks like the ear­ly fa­vorite in colon can­cer with new da­ta, putting the pres­sure square on Am­gen

With Amgen already providing proof-of-concept for KRAS inhibitors with its sotorasib, Mirati Therapeutics is piecing together a follow-up effort in lung cancer with data it thinks are superior. But in colon cancer, where solo sotorasib has turned in a dud, Mirati may now have a strong case for superiority.

Mirati’s adagrasib, dosed solo or in combination with chemotherapy cetuximab, showed numerically higher response rates than sotorasib solo and as part of a combination study in a similar patient population also revealed this week at #ESMO21. Mirati’s data were presented as part of a cohort update from the Phase II KRYSTAL-1 study testing adagrasib in a range of solid tumors harboring the KRAS-G12C mutation.

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Ex­elix­is pulls a sur­prise win in thy­roid can­cer just days ahead of fi­nal Cabome­tyx read­out

Exelixis added a thyroid cancer indication to its super-seller Cabometyx’s label on Friday — months before the FDA was expected to make a decision, and days before the company was set to unveil the final data at #ESMO21.

At a median follow-up of 10.1 months, differentiated thyroid cancer patients treated with Cabometyx (cabozantinib) lived a median of 11 months without their disease worsening, compared to just 1.9 months for patients given a placebo, Exelixis said on Monday.