Sung Joo Lee, Orum Therapeutics CEO

In­vestors give Orum Ther­a­peu­tic­s' unique take on pro­tein de­graders an­oth­er nudge to­ward the clin­ic

While pro­tein de­graders have seen an in­flux of cash in re­cent years, small mol­e­cule drugs can run in­to tox­i­c­i­ty prob­lems, due to their dif­fi­cul­ty dif­fer­en­ti­at­ing healthy cells from can­cer­ous ones, Sung Joo Lee said. His com­pa­ny Orum Ther­a­peu­tics thinks it has a so­lu­tion — and the idea has in­vestors reach­ing a lit­tle deep­er in­to their pock­ets.

Orum closed its Se­ries B round for the sec­ond time on Wednes­day morn­ing, rak­ing in an ex­tra $54 mil­lion. The team had ini­tial­ly raised $30 mil­lion back in 2019, and the suc­ces­sive round came as the re­sult of on­go­ing “or­gan­ic dis­cus­sion” with ex­ist­ing in­vestors, ac­cord­ing to CFO Jae Won Kim.

Jae Won Kim

The com­pa­ny is look­ing to con­ju­gate pro­tein de­graders to an an­ti­body, cre­at­ing first-in-class AD­Cs, or as Orum calls them, AnD­Cs: an­ti­body neode­grad­er con­ju­gates. The con­cept is sim­i­lar to tra­di­tion­al AD­Cs, which con­sist of a can­cer-killing tox­in at­tached to a spe­cif­ic an­ti­body us­ing a biodegrad­able link­er. Ex­cept in this case, the pay­load is a pro­tein de­grad­er.

With pro­tein de­graders, the idea is to make en­tire pro­teins dis­ap­pear us­ing the body’s nat­ur­al garbage dis­pos­al sys­tem. Orum’s pro­tein de­graders de­ploy ubiq­ui­tin tags, which sig­nal the pro­tea­some to pick up the tar­get pro­tein, un­fold it and de­grade it in­to small frag­ments. What’s dif­fer­ent here is that the an­ti­body com­po­nent of the AnDC di­rects the pro­tein de­grad­er right to the cy­tosol — the aque­ous com­po­nent of the cy­to­plasm — of tar­get cells, which Lee thinks could make the drugs safer and more ef­fec­tive than oth­er can­di­dates.

“We are bring­ing a very unique pay­load,” the CEO said. “What we’re do­ing is we’re con­ju­gat­ing to an an­ti­body that is in­ter­nal­ized specif­i­cal­ly to a tu­mor cell so ide­al­ly … with a low­er dose of the drug, we could achieve a high­er ef­fi­ca­cy and low­er risk of tox­i­c­i­ty.”

The com­pa­ny has two lead can­di­dates in the works — ORM-5029 for sol­id tu­mors and ORM-6151 for hema­to­log­i­cal can­cers — which are ex­pect­ed to hit the clin­ic in 2022 and 2023, re­spec­tive­ly. Orum will use the new round — led by IMM In­vest­ment with KDB In­vest­ment, At­inum, In­ter­vest, KB In­vest­ment, and oth­ers chim­ing in — to ad­vance those two can­di­dates to­ward the clin­ic.

A steady stream of fund­ing flowed in­to pro­tein degra­da­tion last year. Back in March, Nurix and Kymera scooped up a to­tal of $222 mil­lion in con­sec­u­tive days. And a month lat­er, Am­phista launched with a $7.5 mil­lion Se­ries A and help from field ex­pert Alessio Ciul­li. C4 Ther­a­peu­tics made the jump to Nas­daq in Oc­to­ber.

Be­fore launch­ing Orum with an $8 mil­lion Se­ries A back in 2017, Lee worked at Sanofi, where he was head of re­search in the Asia Pa­cif­ic R&D unit.

“I felt that some in­no­v­a­tive nov­el plat­forms, they have a more vivid or vi­brant life in a small biotech, so I de­cid­ed to leave Sanofi and start a new com­pa­ny,” he said. “So far it’s been very fo­cused, very quick, and we’ve made a lot of progress so I’m quite hap­py I made that move.”

The lede has been up­dat­ed to clar­i­fy that Lee was re­fer­ring to tox­i­c­i­ty re­lat­ed to small mol­e­cule drugs in gen­er­al.

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.

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.