Robert Doebele and Avanish Vellanki (Rain)

New tar­get­ed ther­a­py ap­proach­es win Rain Ther­a­peu­tics $63M — de­signed to beat a quick path to ap­proval

Rain Ther­a­peu­tics is on a tear.

When the biotech got start­ed in the San Fran­cis­co Bay Area, it was sin­gu­lar­ly fo­cused on tar­lox­o­tinib, a small mol­e­cule in­hibitor named for its de­sign to tar­get low oxy­gen lev­els in the tu­mor and there­by spar­ing healthy tis­sues. More than two years lat­er, Rain has tripled its pipeline with­in days, first li­cens­ing a re­search pro­gram from Drex­el Uni­ver­si­ty, then more re­cent­ly nab­bing a Phase II-ready drug from Dai­ichi Sankyo.

It al­so has $63 mil­lion in fresh fund­ing to push all three pro­grams, with Box­er Cap­i­tal, Cor­morant As­set Man­age­ment, Sam­sara Bio­Cap­i­tal, Janus Hen­der­son In­vestors and Lo­gos Cap­i­tal now in its cor­ner along­side ex­ist­ing in­vestors BVF Part­ners and Per­cep­tive Ad­vi­sors.

Through it all, Rain is re­tain­ing its tar­get­ed fo­cus, not­ed CEO Avan­ish Vel­lan­ki.

Start­ing out with tar­lox­o­tinib, for in­stance, al­lowed them to tap in­to the Ex­on 20 niche with­in the broad­er EGFR-pos­i­tive non-small cell lung can­cer as well as NRG1, EGFR, HER2, and HER4 fu­sions.

Mean­while RAIN-32, the ther­a­py from Dai­ichi Sankyo that has su­per­seded tar­lox­o­tinib as Rain’s lead pro­gram, tar­gets MDM2 (which in­hibits p53, block­ing its tu­mor sup­press­ing ef­fect). The oth­er pre­clin­i­cal pro­gram fo­cus­es on RAD52, which CSO Robert Doe­bele calls a crit­i­cal back­up path­way for can­cer cells that al­ready have oth­er de­fects in the DNA dam­age re­sponse path­way.

A vet­er­an tri­al in­ves­ti­ga­tor well-versed in onco­gene tar­gets who’s con­tin­ued to prac­tice and re­search at the Uni­ver­si­ty of Col­orado af­ter co-found­ing Rain, Doe­bele said new ap­proach­es are need­ed to open up new waves of can­cer treat­ment to fol­low up on the sev­en onco­genes now cov­ered by FDA-ap­proved treat­ments.

“The num­ber of tar­gets that we can di­rect­ly in­hib­it like that — like ALK, EGFR, ROS — are some­what thin­ning a bit,” he said. “But I think these new strate­gies where we’re tar­get­ing the p53 path­way and re­ac­ti­vat­ing or us­ing syn­thet­ic lethal­i­ty strate­gies in a very sim­i­lar way, ba­si­cal­ly tak­ing ad­van­tage of can­cer-spe­cif­ic vul­ner­a­bil­i­ties, is ab­solute­ly of in­ter­est.”

A gen­er­al uptick in next-gen­er­a­tion se­quenc­ing is al­so speed­ing up the iden­ti­fi­ca­tion of pa­tients, as Rain has wit­nessed first­hand with the on­go­ing Phase II for tar­lox­o­tinib.

As with en­trec­tinib and larotrec­tinib for pa­tients with NTRK fu­sions, both of which Doe­bele has helped de­vel­op, Rain be­lieves RAIN-32 lends it­self to tu­mor-ag­nos­tic — or bi­ol­o­gy-dri­ven as he prefers to call it — de­vel­op­ment.

“That’s still a very very young field,” he said.

The Se­ries B gives Rain about 2.5 years of run­way, fu­el­ing its lean team of 8 all the way to the com­ple­tion of a piv­otal tri­al for RAIN-32 in li­posar­co­ma. With­in the sub­pop­u­la­tion the com­pa­ny is fo­cus­ing on, Vel­lan­ki said, near­ly 100% has an MDM2 gene am­pli­fi­ca­tion.

While oth­er com­pa­nies like Roche and As­cen­t­age have de­vel­oped MDM2 in­hibitors, tox­i­c­i­ties re­main a big prob­lem for the field, ac­cord­ing to Vel­lan­ki. Dai­ichi sci­en­tists tried to solve for that with a dif­fer­ent dos­ing sched­ule that gives pa­tients time to re­cov­er from the side ef­fects.

“Broad­ly speak­ing when­ev­er you have ver­sion 2.0 or ver­sion 3.0 of any tech­nol­o­gy, you’re able to com­pen­sate for the prob­lems of the ver­sion 1.0,” he said. “Ad­vance­ments of tech­nol­o­gy al­ways al­low you to fine-tune tech­nolo­gies to solve the prob­lems that you didn’t know were there in the first place with the ini­tial set of tar­get­ed ther­a­pies.”

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA have vowed not to let politics get in the way of science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped health agencies under his purview — including the FDA — of their rulemaking ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Dan Skovronsky, Eli Lilly CSO

UP­DAT­ED: An­a­lysts are quick to pan Eli Lil­ly's puz­zling first cut of pos­i­tive clin­i­cal da­ta for its Covid-19 an­ti­body

Eli Lilly spotlighted a success for one of 3 doses of their closely-watched Covid-19 antibody drug Wednesday morning. But analysts quickly highlighted some obvious anomalies that could come back to haunt the pharma giant as it looks for an emergency use authorization to launch marketing efforts.

The pharma giant reported that LY-CoV555, developed in collaboration with AbCellera, significantly reduced the rate of hospitalization among patients who were treated with the antibody. The drug arm of the study had a 1.7% hospitalization rate, compared to 6% in the control group, marking a 72% drop in risk.

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Eli Lilly CSO Dan Skovronsky (file photo)

#ES­MO20: Eli Lil­ly shows off the da­ta for its Verzenio suc­cess. Was it worth $18 bil­lion?

The press release alone, devoid of any number except for the size of the trial, added nearly $20 billion to Eli Lilly’s market cap back in June. Now investors and oncologists will get to see if the data live up to the hype.

On Sunday at ESMO, Eli Lilly announced the full results for its Phase III MonarchE trial of Verzenio, showing that across over 5,000 women who had had HR+, HER2- breast cancer, the drug reduced the odds of recurrence by 25%. That meant 7.8% of the patients on the drug arm saw their cancers return within 2 years, compared with 11.3% on the placebo arm.

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Greg Friberg (File photo)

#ES­MO20: Am­gen team nails down sol­id ear­ly ev­i­dence of AMG 510’s po­ten­tial for NSCLC, un­lock­ing the door to a wave of KRAS pro­grams

The first time I sat down with Amgen’s Greg Friberg to talk about the pharma giant’s KRAS G12C program for sotorasib (AMG 510) at ASCO a little more than a year ago, there was high excitement about the first glimpse of efficacy from their Phase I study, with 5 of 10 evaluable non-small cell lung cancer patients demonstrating a response to the drug.

After decades of failure targeting KRAS, sotorasib offered the first positive look at a new approach that promised to open a door to a whole new approach by targeting a particular mutation to a big target that had remained “undruggable” for decades.

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#ES­MO20: Out to beat Tagris­so, J&J touts 100% ORR for EGFR bis­pe­cif­ic/TKI com­bo — fu­el­ing a quick leap to PhI­II

J&J’s one-two punch on EGFR-mutant non-small cell lung cancer has turned up some promising — although decidedly early — results, fueling the idea that there’s yet room to one up on third-generation tyrosine kinase inhibitors.

Twenty out of 20 advanced NSCLC patients had a response after taking a combination of an in-house TKI dubbed lazertinib and amivantamab, a bispecific antibody targeting both EGFR and cMET engineered on partner Genmab’s platform, J&J reported at ESMO. All were treatment-naïve, and none has seen their cancer progress at a median follow-up of seven months.

#ES­MO20: As­traZeneca aims to spur PRO­found shift in prostate can­cer treat­ment with Lyn­parza OS da­ta

AstraZeneca has unveiled the final, mature overall survival data that cemented Lynparza’s first approval in prostate cancer approval — touting its lead against rivals with the only PARP inhibitor to have demonstrated such benefit.

But getting the Merck-partnered drug to the right patients remains a challenge, something the companies are hoping to change with the new data cut.

The OS numbers on the subgroup with BRCA1/2 or ATM-mutated metastatic castration-resistant prostate cancer are similar to the first look on offer when the FDA expanded the label in May: Lynparza reduced the risk of death by 31% versus Xtandi and Zytiga. Patients on Lynparza lived a median of 19.1 months, compared to 14.7 months for the anti-androgen therapies (p = 0.0175).

#ES­MO20: It’s not just Keytru­da any­more — Mer­ck spot­lights 3 top ear­ly-stage can­cer drugs

Any $12 billion megablockbuster in the portfolio tends to overshadow everything else in the pipeline. Which is something Merck can tell you a little bit about.

Keytruda not only dominates the PD-(L)1 field, it looms over everything Merck does, to the point some analysts wonder if Merck is a one-trick pony.

There’s no shortage of Keytruda data on display at ESMO this weekend, but now the focus is shifting to the future role of new drugs and combos in maintaining that lead position for years to come. And the pharma giant has a special focus for 3 early-stage efforts where Roger Perlmutter’s oncology team is placing some big bets.

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Exelixis CEO Michael Morrissey (file photo)

#ES­MO20: Look out Mer­ck. Bris­tol My­ers and Ex­elix­is stake out their com­bo’s claim to best-in-class sta­tus for front­line kid­ney can­cer

Now that the PD-(L)1 checkpoints are deeply entrenched in the oncology market, it’s time to welcome a wave of combination therapies — beyond chemo — looking to extend their benefit to larger numbers of patients. Bristol Myers Squibb ($BMY} and Exelixis {EXEL} are close to the front of that line.

Today at ESMO the collaborators pulled the curtain back on some stellar data for their combination of Opdivo (the PD-1) and Cabometyx (the TKI), marking a significant advance for the blockbuster Bristol Myers franchise while offering a big leg up for the team at Exelixis.

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Donald Trump and White House chief of staff Mark Meadows, before boarding Marine One (Getty Images)

Pric­ing deal col­laps­es over Big Phar­ma's re­fusal to is­sue $100 'cash card­s' be­fore the elec­tion — re­port

Late in August, as negotiations on a pricing deal with President Trump reached a boiling point, PhRMA president Stephen Ubl sent an email update to the 34 biopharma chiefs that sit on his board. He wrote that if the industry did not agree to pay for a $100 “cash card” sent to seniors before November, White House chief of staff Mark Meadows was going to tell the news media Big Pharma was refusing to “share the savings” with the elderly — and that all of the blame for failed drug pricing negotiations would lie squarely on the industry.