Pal­la­dio bags $20 mil­lion Se­ries B to top­ple a prob­lem­at­ic kid­ney dis­ease drug

Pal­la­dio Bio­sciences just took one step fur­ther in its quest to top­ple Ot­su­ka’s Sam­sca with its own — it hopes safer — au­to­so­mal dom­i­nant poly­cys­tic kid­ney dis­ease (ADP­KD) drug.

Alex Mar­tin

The Penn­syl­va­nia-based biotech an­nounced a $20 mil­lion Se­ries B on Fri­day, which will fund a 10-per­son Phase III tri­al of its va­so­pressin V2 re­cep­tor ag­o­nist, lix­i­vap­tan. CEO Alex Mar­tin ex­pects to read out da­ta in the first half of next year, then launch straight in­to a larg­er piv­otal Phase III study with about 1,200 par­tic­i­pants.

The small­er study is cur­rent­ly en­rolling pa­tients ages 18-65 who ex­pe­ri­enced liv­er chem­istry ab­nor­mal­i­ties or signs of liv­er tox­i­c­i­ty while on tolvap­tan, the gener­ic name of a brand pri­marly known as Sam­sca or Jy­nar­que.

“The on­ly ap­proved treat­ment right now for pa­tients with ADP­KD is tolvap­tan, and that is as­so­ci­at­ed with sig­nif­i­cant liv­er tox­i­c­i­ty. So if you had a drug that… had the same ef­fi­ca­cy as tolvap­tan, but didn’t have sig­nif­i­cant liv­er tox­i­c­i­ty, that would be a safer and bet­ter al­ter­na­tive for pa­tients,” Mar­tin said. In 2013 the FDA up­dat­ed the drug la­bel on Sam­sca to lim­it its use for a max­i­mum of 30 days be­cause of se­ri­ous liv­er in­jury po­ten­tial.

The hor­mone va­so­pressin nor­mal­ly helps reg­u­late wa­ter bal­ance in the body. But in ADP­KD pa­tients, it al­so has a hand in cyst growth. The goal is to in­hib­it cyst growth and de­crease flu­id se­cre­tion in­to cysts by sup­press­ing va­so­pressin at the V2 re­cep­tor, ac­cord­ing to Pal­la­dio.

Just over a year ago, the com­pa­ny be­gan a com­pas­sion­ate use study of lix­i­vap­tan in a pa­tient who re­act­ed neg­a­tive­ly to tolvap­tan.

Four­teen months lat­er, the pa­tient was “ab­solute­ly spot­less,” Mar­tin said. “No prob­lems at all with her liv­er.” Now the ques­tion is — can this anec­do­tal re­sult play out in a clin­i­cal tri­al?

In a Phase II study, dubbed ELiSA, pa­tients treat­ed with lix­i­vap­tan showed a mean urine os­mo­lal­i­ty (Uosm) de­cline of 80% in the hours af­ter their first dose. And all pa­tients with Stage 2 and 3 chron­ic kid­ney dis­ease main­tained a Uosm be­low 300 mOsm/kg over 24 hours, ac­cord­ing to the re­sults. One tolvap­tan study showed that the drug achieved a Uosm be­low 300 mOsm/kg in 81% of pa­tients.

“If you take lix­i­vap­tan for many years, you could the­o­ret­i­cal­ly de­lay your pro­gres­sion to dial­y­sis for 5 to 10 years, or even push it off al­to­geth­er so that you wouldn’t need it,” Mar­tin said.

The Se­ries B haul will fund the en­tire first Phase III tri­al, called ALERT, which will as­sess safe­ty. Mar­tin said he ex­pects to be­gin dos­ing ADP­KD pa­tients for that study in Q4 of this year. The sec­ond, larg­er study will like­ly be a three-year-tri­al, he said.

The fi­nanc­ing round was led by new in­vestor Sam­sara Bio­Cap­i­tal. Pre­vi­ous in­vestors Medicxi and Os­age Uni­ver­si­ty Part­ners jumped in, as well as an­oth­er new in­vestor, the RocheVen­ture Fund.

Pal­la­dio was found­ed in 2015 by Care Cap­i­tal vet Loren­zo Pel­le­gri­ni. The Pal­la­dio COO has co-found­ed sev­er­al port­fo­lio com­pa­nies, in­clud­ing Waltham, Mass­a­chu­setts-based Min­er­va Neu­ro­sciences. Mar­tin was pre­vi­ous­ly CEO at Realm Ther­a­peu­tics, which was snatched up by ES­SA last year. He was al­so COO at In­ter­cept Phar­ma­ceu­ti­cals, and CFO at BioX­ell, which was bought by Cos­mo Phar­ma­ceu­ti­cals for $41 mil­lion in 2009.

In his­toric Covid-19 ad­comm, vac­cine ex­perts de­bate a sea of ques­tions — but of­fer no clear an­swers

The most widely anticipated and perhaps most widely watched meeting in the FDA’s 113-year history ended late Thursday night with a score of questions and very few answers.

For nearly 9 hours, 18 different outside experts listened to public health agencies and foundations present how the United States’ Covid-19 vaccine program developed through October, and they debated where it should go from there: Were companies testing the right metrics in their massive trials? How long should they track patients before declaring a vaccine safe or effective? Should a vaccine, once authorized, be given to the volunteers in the placebo arm of a trial?

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Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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A top drug pro­gram at Bay­er clears a high bar for CKD — open­ing the door to an FDA pitch

Over the past 4 years, Bayer has been steering a major trial through a pivotal program to see if their drug finerenone could slow down the pace of chronic kidney disease in patients suffering from both CKD as well as Type 2 diabetes.

Today, their team jumped on a virtual meeting hosted by the American Society of Nephrology to offer a solid set of pivotal data to demonstrate that the drug can delay dialysis or a kidney replacement as well as cardio disease, while also adding some worrying signs of hyperkalemia among the patients taking the drug. And they’re hustling it straight to regulators in search of an approval for kidney disease and cardio patients — one of the toughest challenges in the book, as demonstrated by repeated past failures.

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Biond­Vax stock im­plodes af­ter a big PhI­II gam­ble for its uni­ver­sal flu vac­cine fails

After flying high on Wall Street for the last few months of a pandemic, BiondVax’s stock and dreams of getting approval for its universal flu vaccine hit the windshield.

The Jerusalem-based biotech announced on Friday that its only clinical candidate, M-001, failed both primary and secondary endpoints in a Phase III study. There was no statistically significant difference in reduction of flu illness and severity between the vaccine and placebo groups, according to the company. The vaccine did prove safe, if ineffective, BiondVax said.

Pascal Soriot, AstraZeneca CEO (Zach Gibson/Bloomberg via Getty Images)

UP­DAT­ED: FDA gives As­traZeneca the thumbs-up to restart PhI­II Covid-19 vac­cine tri­als, and J&J is prepar­ing to re­sume its study

Several countries had restarted their portions of AstraZeneca’s global Phase III Covid-19 vaccine trial after the study was paused worldwide in early September, but the US notably stayed on the sidelines — until now. Friday afternoon the pharma giant announced the all clear from US regulators. And on top of that, J&J announced Friday evening that it’s preparing to resume its own Phase III vaccine trial.

Ul­tragenyx in­jects $40M to grab Solid's mi­crody­s­trophin trans­gene — while side­step­ping the AAV9 vec­tor that stirred up safe­ty fears

Since before Ilan Ganot started Solid Bio to develop a gene therapy for kids like his son, who has Duchenne muscular dystrophy, Ultragenyx CEO Emil Kakkis has been watching and advising the former investment banker as he navigated the deep waters of drug development.

Just as Solid is getting back up on its feet after a yearlong clinical hold, Kakkis has decided to jump in for a formal alliance.

With a $40 million upfront, Ultragenyx is grabbing 14.45% of Solid’s shares $SLDB and the rights to its microdystrophin construct for use in combination with AAV8 vectors. Solid’s lead program, which utilizes AAV9, remains unaffected. The company also retains rights to other applications of its transgene.

Adam Koppel and Jeffrey Schwartz, Bain

Bain ex­ecs Adam Kop­pel and Jef­frey Schwartz line up $125M for their first blank check deal as Wall Street con­tin­ues to em­brace biotech

Adam Koppel and Jeffrey Schwartz have jumped into the blank check game, raising $125 million for a stock listing in search of a company.

Their SPAC, BCLS Acquisition Corp, raised $125 million this week, with a line on $25 million more as it scouts for a biotech in search of money and a place on Wall Street.

The two principals at Bain Life Sciences have been on a romp since they set up the Bain operation 4 years ago. Their S-1 spells out a track record of 22 deals totaling $650 million for the life sciences group, which led to 9 IPOs.

Covid-19 roundup: An mR­NA play­er gets a boost out of the lat­est round of an­i­mal da­ta; Phase­Bio pulls the plug on treat­ment tri­al

The big tell for CureVac $CVAC is coming up with a looming early-stage readout on their mRNA Covid-19 vaccine in the clinic. But for now they’ll make do with an upbeat assessment on the preclinical animal data they used to get into the clinic.

Researchers for the German biotech say they got the high antibody titers and T cell activation they were looking for, lining up a hamster challenge to demonstrate — in a simple model — that the vaccine could protect the furry creatures. Like the other mRNA vaccines, the drug sends instructions to spur cells to decorate themselves with the distinctive spike on the virus to elicit an immune response.

Chi­nese in­vestors wa­ger $105M on an IPO-bound biotech look­ing to push RNAi as main­stream can­cer ther­a­py

Shortly after Sirnaomics brought in a $47 million Series C for its small interfering RNA pipeline last year, Patrick Lu — the founder, president and CEO — was asked to outline the scientific advances that will be necessary to make better drugs out of RNA tech.

“The next step in the evolution of RNAi as a leading therapeutic will be the ability to safely target organs outside the liver such as lung, brain, etc,” he had offered. “This will revolutionize disease treatments if the industry can demonstrate similar data sets for non-liver targets as we have seen in liver-based diseases.”