Victoria Richon (Ribon Therapeutics)

Ri­bon Ther­a­peu­tics is look­ing to break the mold for PARP in­hibitors and has a slate of Big Phar­ma back­ers on board

Ri­bon Ther­a­peu­tics broke three years of ra­dio si­lence back in ear­ly 2019 to spread the word of its $65 mil­lion Se­ries B round. Now, two and a half years lat­er, the com­pa­ny’s lead PARP in­hibitor has in­vestors reach­ing a lit­tle deep­er in­to their pock­ets.

CEO Vic­to­ria Ri­chon un­veiled a $65 mil­lion Se­ries B1 round on Wednes­day, which she de­scribed as an ex­ten­sion of the B round closed at the end of 2018. The lat­est round, led by Deer­field Man­age­ment and US Ven­ture Part­ners, brings the Cam­bridge, MA-based biotech’s to­tal raise up to about $175 mil­lion. A slate of Big Phar­ma play­ers al­so chipped in, in­clud­ing Ab­b­Vie Ven­tures, Bris­tol My­ers Squibb, John­son & John­son In­no­va­tion, Take­da Ven­tures and the No­var­tis Ven­ture Fund.

When asked if a pub­lic de­but is in Ri­bon’s fu­ture, Ri­chon, a Sanofi vet, re­spond­ed: “This fi­nanc­ing en­ables us to move our cur­rent pro­grams for­ward, and we’re al­ways go­ing to be eval­u­at­ing all op­por­tu­ni­ties avail­able to us to con­tin­ue to ad­vance Ri­bon on as a com­pa­ny, and to bring our pro­grams to as many pa­tients as we can, and as quick­ly as pos­si­ble.”

For now, the ex­tra cash will sup­port the com­pa­ny’s two lead pro­grams: a Phase I PARP7 in­hibitor dubbed RBN-2397 in can­cer, and a pre­clin­i­cal PARP14 in­hibitor called RBN-3143 in in­flam­ma­tion.

The grow­ing class of PARP in­hibitors on the mar­ket in­cludes As­traZeneca and Mer­ck’s Lyn­parza, Pfiz­er’s Talzen­na, Clo­vis’ Rubra­ca and Glax­o­SmithK­line’s Ze­ju­la. They all pri­mar­i­ly tar­get PARP1 (with some al­so in­hibit­ing PARP2 and PARP3), which is a pro­tein used by dam­aged cells to ini­ti­ate re­pair. Un­like those drugs, RBN-2397 tar­gets PARP7, a dif­fer­ent pro­tein sim­i­lar­ly ac­ti­vat­ed by stress and cel­lu­lar re­sponse mech­a­nisms. By block­ing PARP7, the can­di­date is de­signed to en­able tu­mor cells to se­crete in­ter­fer­on, restor­ing Type I in­ter­fer­on sig­nal­ing.

“We look at our­selves as pi­o­neers,” Ri­chon told End­points News up­on an­nounc­ing the Se­ries B in ear­ly 2019.

At #AS­CO21, Ri­bon pre­sent­ed in­ter­im Phase I da­ta that showed RBN-2397 was well-tol­er­at­ed and showed pre­lim­i­nary an­ti­tu­mor ac­tiv­i­ty in pa­tients with sol­id tu­mors. In the heav­i­ly pre­treat­ed pop­u­la­tion, one par­tial re­sponse was ob­served in a pa­tient with HR+ breast can­cer, and nine oth­ers achieved sta­ble dis­ease af­ter four months, ac­cord­ing to Ri­bon.

Ri­chon says the team has com­plet­ed the dose-es­ca­la­tion por­tion of that tri­al and is just now get­ting in­to ex­pan­sion co­horts. RBN-3143, on the oth­er hand, is an­tic­i­pat­ed to en­ter clin­i­cal test­ing next year.

“We know that cel­lu­lar stress plays a ma­jor role in many dis­eases,” Ri­chon said. “And so we’re pi­o­neer­ing the de­vel­op­ment of first-in-class small mol­e­cule in­hibitors against this ex­tend­ed PARP fam­i­ly of en­zymes, and re­al­ly have found very im­por­tant new bi­ol­o­gy as now shown with RBN-2397 and RBN-3143.”

Avego Bio­Science Cap­i­tal, GV (for­mer­ly Google Ven­tures), Monashee In­vest­ment Man­age­ment, Pere­grine Ven­tures, Eu­clid­ean Cap­i­tal, Os­age Uni­ver­si­ty Part­ners and The Col­umn Group al­so chipped in­to the Se­ries B1 round.

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

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Next week is shaping up to be a busy one, as our editor-in-chief John Carroll and managing editor Kyle Blankenship lead back-to-back discussions with a great group of experts to discuss the weekend news and trends. John will be spending 30 minutes with Jake Van Naarden, the CEO of Lilly Oncology, and Kyle has a brilliant panel lined up: Harvard’s Cigall Kadoch, Susan Galbraith, the new head of cancer R&D at AstraZeneca, Roy Baynes at Merck, and James Christensen at Mirati. Don’t miss out on the action — sign up here.

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Mi­rati's KRAS drug looks like the 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 response rates grater than sotorasib solo  and as part of 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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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.

The best of the rest: High­lights from the be­low-the-fold pre­sen­ta­tions at #ES­MO21

This year’s ESMO Congress has had a major focus on Big Pharma drugs — most notably candidates from Merck and AstraZeneca — but there have also been updates from smaller biotechs with data looking to challenge the big-name drugmakers.

Today, we’re highlighting some of the data releases that flew under the radar at #ESMO21 — whether from early-stage drugs looking to make a mark or older stalwarts with interesting follow-up data.

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.

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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.