Sean McCarthy, CytomX CEO

Cy­tomX halts lead pro­gram and will seek a part­ner as breast can­cer drug dis­ap­points

Mixed Phase II re­sults are forc­ing Cy­tomX to slam the brakes on one of its lead can­cer drugs — un­less it can con­vince a part­ner to help take it fur­ther.

The da­ta come from a study of praluzatam­ab rav­tan­sine, Cy­tomX’s take on a CD166-tar­get­ing an­ti­body-drug con­ju­gate, in breast can­cer that com­prised three sep­a­rate arms: Arm A fo­cused on hor­mone re­cep­tor-pos­i­tive, HER2-non-am­pli­fied pa­tients; Arm B and C both re­cruit­ed pa­tients with triple-neg­a­tive breast can­cer, but the for­mer test­ed the drug as a monother­a­py and Arm C gave it in com­bi­na­tion with an in-house an­ti-PD-L1 drug dubbed pacmil­imab.

In­ves­ti­ga­tors tracked pos­i­tive re­sults in Arm A, where the ther­a­py met the pri­ma­ry end­point with an over­all re­sponse rate of more than 10%. Among 47 pa­tients, the ORR was 15%, and on the sec­ondary end­points, clin­i­cal ben­e­fit rate at 24 weeks was 40% and me­di­an pro­gres­sion-free sur­vival was 2.6 months.

Arm B, how­ev­er, failed to pass the fu­til­i­ty bound­ary that Cy­tomX set as ORR was less than 10%. As a re­sult, the biotech says it will stop en­rolling new pa­tients in­to both Arms B and C.

“It seems to us that con­di­tion­al ac­ti­va­tion Pro­body tech­nol­o­gy has demon­strat­ed tech­ni­cal util­i­ty but the re­sults in HR+ breast can­cer make it chal­leng­ing to see ad­vance­ment giv­en the com­pet­i­tive dy­nam­ics in the HR+ breast can­cer mar­ket, which has been a con­cern for us,” Mizuho an­a­lyst Mara Gold­stein wrote in a note. “We don’t dis­agree with the de­ci­sion to halt de­vel­op­ment, but we al­so do not have high ex­pec­ta­tions for a part­ner­ship.”

In the wake of the set­back, shares $CT­MX fell 22% to $1.51 af­ter the bell Wednes­day.

To make things more com­pli­cat­ed, Cy­tomX ac­tu­al­ly test­ed two dif­fer­ent dos­es in the study: While Arm A ex­clu­sive­ly gave 7 mg/kg, Arm B as­sessed both 6 mg/kg and 7mg/kg, and Arm C stud­ied on­ly the low­er-dose reg­i­men.

In Arm A, 30% of pa­tients dis­con­tin­ued treat­ment for an ad­verse event, and the com­pa­ny re­port­ed Grade 3+ oc­u­lar and neu­ro­path­ic tox­i­c­i­ties of 15% and 10%, re­spec­tive­ly. In con­trast, the 6 mg/kg dose was tied to much low­er tox­i­c­i­ty.

“These re­sults from our Phase II eval­u­a­tion of praluzatam­ab rav­tan­sine sup­port sin­gle-agent ac­tiv­i­ty of this nov­el drug can­di­date in hor­mone re­cep­tor-pos­i­tive breast can­cer where sig­nif­i­cant un­met need re­mains,” CEO Sean Mc­Carthy said in a state­ment. “How­ev­er, we do not be­lieve the me­di­an pro­gres­sion-free sur­vival at 7 mg/kg sup­ports fur­ther eval­u­a­tion at this dose. While we are en­cour­aged by the emerg­ing safe­ty pro­file of 6 mg/kg, we do not plan to fur­ther ad­vance this pro­gram alone giv­en cur­rent fi­nan­cial mar­ket con­di­tions and will be seek­ing a part­ner­ship.”

Cy­tomX has inked mul­ti­ple al­liances with Big Phar­ma part­ners over the years on the al­lure of its Pro­body tech­nol­o­gy, which cen­ters around a mask­ing pep­tide on drugs al­low­ing for ac­ti­va­tion un­der the right con­di­tions, the­o­ret­i­cal­ly al­le­vi­at­ing safe­ty con­cerns. Praluzatam­ab rav­tan­sine, al­so known as CX-2009, is of­ten re­ferred to as a Pro­body-drug con­ju­gate be­cause it us­es one such con­di­tion­al­ly ac­ti­vat­ed an­ti­body to home in on can­cer. The an­ti­body is con­ju­gat­ed to the may­tansi­noid DM4, a tubu­lin in­hibitor.

But the Pro­body tech has yet to lead to any mar­ket­ed drug and Pfiz­er chose to drop out of its deal in 2018. Oth­ers like Ab­b­Vie, Bris­tol My­ers Squibb, Am­gen and Astel­las, though, are mov­ing for­ward with var­i­ous can­di­dates.

Cy­tomX says it will con­tin­ue to an­a­lyze bio­mark­er da­ta and plans to present more find­ings lat­er. The com­pa­ny’s next da­ta read­out will come from the Ab­b­Vie-part­nered CX-2029, a Pro­body-drug con­ju­gate that tar­gets CD71, in squa­mous non-small cell lung can­cer.

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; 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.

With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

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Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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Sanofi scraps PhI­II tri­al for Prin­cip­ia drug af­ter re­view­ing com­pe­ti­tion

Months after the FDA placed Phase III trials of Sanofi’s BTK inhibitor on hold, the company is winding down one of the studies.

Sanofi reported in its Q4 earnings that the URSA study “was discontinued after careful evaluation of the emerging competitive treatment landscape in” myasthenia gravis, a rare disease that causes muscle weakness.

The Phase III, placebo-controlled trial was testing tolebrutinib in patients with the moderate-to-severe form of the disease. It started in late 2021, according to records on clinicaltrials.gov, and was originally designed to recruit 154 participants who were receiving the standard of care.

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Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

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How to use ex­ter­nal con­trols: FDA spells out think­ing in new draft guid­ance

The use of real-world evidence to inform the FDA’s decision-making continues apace, with the agency releasing new draft guidance yesterday on how sponsors can compare outcomes of trial participants receiving a test treatment with outcomes in a group of people external to the trial.

The practice of externally controlled trials is common, particularly in oncology or other difficult areas where it’s not ethical or feasible to use internal controls.

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The Big Phar­ma axe: Mer­ck cuts chikun­gun­ya vax, Bris­tol My­ers drops Cy­tomX-part­nered pro­gram, and more

As fourth quarter earnings come in, Big Pharmas are disclosing changes to their pipelines during their investor calls, and sometimes more quietly in presentation appendices.

Merck dropped its chikungunya vaccine candidate, which completed a Phase II study. Merck acquired the vaccine through its purchase of Themis Bioscience in 2020. In developing a vaccine for chikungunya, a mosquito-borne virus, Valneva is the frontrunner, as it submitted its vaccine to the FDA at the end of December.

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