Nek­tar, stung by new in­vestor law­suit over IL-2 drug, se­cures $150M for Keytru­da com­bo piv­otal tri­al

Nek­tar Ther­a­peu­tics’ IL-2 drug hasn’t al­ways lived up to ex­pec­ta­tions in the four and a half years since it scored a promi­nent al­ly in Bris­tol My­ers Squibb — a pact that even­tu­al­ly bal­looned to $3.6 bil­lion.

The ear­ly da­ta snap­shots for a com­bo of be­m­pe­galdesleukin, or NK­TR-214, with Op­di­vo, in par­tic­u­lar, rat­tled in­vestors, and the biotech’s ex­pla­na­tion, pin­ning the blame on man­u­fac­tur­ing, did lit­tle to sal­vage their stock price. In fact, just yes­ter­day, two share­hold­ers sued the board of di­rec­tors for hyp­ing tri­al re­sults and then sell­ing $171 mil­lion worth of stock at an in­flat­ed price.

But it hasn’t stopped new part­ners from see­ing the po­ten­tial in this par­tic­u­lar I/O add-on to the main­stay check­point in­hibitors.

Mer­ck has jumped in for an ex­pand­ed col­lab­o­ra­tion to test Keytru­da with be­m­peg in a reg­is­tra­tional tri­al for squa­mous cell car­ci­no­ma of the head and neck, adding to a slate of on­go­ing Phase III pro­grams Nek­tar has with Bris­tol My­ers. And they won’t be run­ning the tri­al on their own dime; Abing­worth and Black­stone have promised, through their SFJ Phar­ma­ceu­ti­cals sub­sidiary, to bankroll the study with a com­mit­ment of up to $150 mil­lion.

In re­turn, Nek­tar would pay suc­cess-based an­nu­al mile­stone pay­ments over sev­en to eight years — but on­ly if be­m­peg is ap­proved for the spec­i­fied in­di­ca­tions.

The head and neck can­cer study — which fol­lows a dose op­ti­miza­tion study ex­plor­ing Keytru­da plus be­m­peg across a suite of can­cers in­clud­ing melanoma, non-small cell lung can­cer and urothe­lial car­ci­no­ma — is ex­pect­ed to wrap up in 2024.

Jonathan Za­levsky

“Ear­li­er stud­ies of BE­M­PEG in com­bi­na­tion with im­mune check­point in­hibitors, al­so known as ICIs, eval­u­at­ed in pa­tients with im­mune-sen­si­tive can­cers have shown the po­ten­tial to in­crease and deep­en treat­ment re­spons­es as com­pared to his­tor­i­cal rates for ICIs alone,” Jonathan Za­levsky, chief R&D of­fi­cer at Nek­tar, said in a state­ment.

Mer­ck’s PD-1, he added, is the lead­ing check­point in­hibitor in the set­ting of ad­vanced head and neck can­cer.

Bri­an Kotzin

The Nek­tar team led by Za­levsky and Bri­an Kotzin, who re­cent­ly re­placed Wei Lin as head of de­vel­op­ment, is tasked with plan­ning and car­ry­ing out the tri­al start­ing lat­er this year, which will tar­get 500 pa­tients with metasta­t­ic or un­re­sectable re­cur­rent SC­CHN whose tu­mors ex­press PD-L1.

With piv­otal Op­di­vo/be­m­peg da­ta loom­ing for can­cers of the skin, kid­ney and blad­der, they are bank­ing on a pipeline re­bound af­ter Nek­tar chopped an opi­oid pro­gram and sold off roy­al­ties to their two mar­ket­ed drugs to fo­cus on the I/O branch.

Back in 2019 CEO Howard Robin as­sured in­vestors that the “soft­en­ing up” of re­spons­es ob­served in the ear­ly tri­als had to do with a sub­op­ti­mal batch of drug ma­te­r­i­al. And he promised it won’t hap­pen again.

An­a­lysts aren’t ready to buy in just yet, es­pe­cial­ly giv­en the fierce com­pe­ti­tion from all the new play­ers that have shown up on the IL-2 scene.

As SVB Leerink an­a­lyst Daina Gray­bosch wrote in a re­cent note:

Pre­sen­ta­tions at re­cent sci­en­tif­ic con­fer­ences high­light the promise of Nek­tar’s ear­ly pipeline, but in­vestors have made up their mind on the promise of be­m­pe­galdesleukin and we ex­pect the stock to re­main stub­born­ly flat un­til ran­dom­ized da­ta — slip­ping an­oth­er quar­ter to 2022.

Billed as a CD122-pref­er­en­tial IL-2 path­way ag­o­nist, be­m­peg is de­signed to un­leash the can­cer-killing sig­nal while keep­ing tox­i­c­i­ty low enough for out­pa­tient ad­min­is­tra­tion.

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; and more

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President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

Mer­ck flesh­es out Keytru­da win in first-line cer­vi­cal can­cer, adding more fire­pow­er to its ear­ly can­cer push

Merck has worked hard to bring its I/O blockbuster Keytruda into earlier and earlier lines of therapy, and now the wonder drug appears poised to make a quick entry into early advanced cervical cancer.

A combination of Keytruda and chemotherapy with or without Roche’s Avastin cut the risk of death by 33% over chemo with or without Avastin (p=<0.001) in first-line patients with persistent, recurrent or metastatic cervical cancer, according to full data from the Phase III KEYNOTE-826 study presented Saturday at #ESMO21.

Chi­nese biotech Ever­est signs $550M+ li­cens­ing deal for BTK in­hibitors on heels of Covid-19 pact

Everest Medicines is on a roll with two licensing deals in one week.

The Shanghai-based biotech has paid Sinovent and SinoMab $12 million upfront for the rights to a BTK inhibitor for renal diseases, the company announced Thursday. The deal comes just days after Everest came away with rights to a Covid-19 vaccine in China, Taiwan, Singapore, Thailand and Indonesia.

Everest will pay Sinovent and SinoMab up to $549 million in milestone payments and royalties. The agreement includes tech transfer of Sinovent and SinoMab’s manufacturing process for the candidate, named XNW1011.

Gri­fols drops $1B on Ger­man hold­ing com­pa­ny in con­tin­ued plas­ma push

One Spanish biotech is beefing up its plasma therapy operations, and on Friday, it announced that it’s doing so in a billion-dollar deal.

Grifols is now the largest shareholder of Biotest, a company valued at more than $1.8 billion. By teaming up, the two will try to increase the number of plasma therapies available and increase patient access around the world, Grifols said in a press release.

The company did so by acquiring holding company Tiancheng Pharmaceutical, the Germany-based owner of nearly 90% of Biotest shares, for nearly $1.27 billion. Grifols now owns nearly 90% of Biotest voting rights and almost 45% of the total share capital of Biotest.