Randall Schatzman, Bolt CEO

Bolt throws a wrench in the pipeline, look­ing to con­serve cash

A melt­down in the biotech mar­ket is mak­ing most ex­ecs cau­tious, in­clud­ing Bolt Bio­ther­a­peu­tics’ CEO, as the com­pa­ny hits the brakes on one pre­clin­i­cal as­set and paus­es oth­er ear­ly-stage work to ex­tend cash re­serves by two years.

The pipeline re-org will keep Bolt’s lights on through 2025 so the biotech can fo­cus on its clin­i­cal-stage HER2 sol­id tu­mor drug can­di­date, which the com­pa­ny should have ear­ly-stage da­ta on and a rec­om­mend­ed Phase II dose by year’s end. The biotech al­so wants to fo­cus on its pre­clin­i­cal as­set BDC-3042,  for KRAS and TP53 mu­tat­ed tu­mors.

That means Bolt has flashed the red light on BDC-2034, which tar­gets car­ci­noem­bry­on­ic anti­gen cell ad­he­sion mol­e­cule 5 (CEA). Bolt’s de­ci­sion to dis­con­tin­ue BDC-2034 was based on off-tar­get tox­i­c­i­ty re­lat­ed to the tar­get­ing an­ti­body. The com­pa­ny had pre­vi­ous­ly planned for BDC-2034 to en­ter the clin­ic in 2023.

SVB Se­cu­ri­ties an­a­lyst Daina Gray­bosch not­ed on Aug. 11 that “the dis­con­tin­u­a­tion is an­oth­er il­lus­tra­tion that im­munos­tim­u­la­to­ry an­ti­body-drug con­ju­ga­tion (ISAC) is a dif­fi­cult drug plat­form, and we ex­pect ex­ten­sive prod­uct it­er­a­tion and back-trans­la­tion will be re­quired in this nascent stage of ISAC de­vel­op­ment.”

The com­pa­ny will bring in a heavy fo­cus on BDC-1001 and BDC-3042 go­ing for­ward. BDC-1001, an an­ti­body con­ju­gate drug, is de­signed to ramp up the body’s in­nate im­mune sys­tem re­sponse to tu­mors. Last year, the com­pa­ny had post­ed a sin­gle par­tial re­sponse in a Phase I/II study in pa­tients with HER2-ex­press­ing sol­id tu­mors af­ter a year of dos­ing. Just 13 of 40 evalu­able pa­tients showed any signs of “clin­i­cal ac­tiv­i­ty,” the biotech had said. The drug is be­ing test­ed as a monother­a­py and in com­bi­na­tion with Op­di­vo, Bris­tol My­ers Squibb’s check­point in­hibitor, Bolt said.

BDC-3042, on the oth­er hand, is a myeloid mod­u­lat­ing ag­o­nist an­ti­body that “reawak­ens” myeloid cells to at­tack can­cer cells. The drug binds to Dectin-2, a nov­el cell sur­face pro­tein on macrophages, which caus­es the pro­duc­tion of pro-in­flam­ma­to­ry cy­tokines. The com­pa­ny hopes to en­ter hu­man tri­als with the drug next year.

“We have a lot to look for­ward to with strong in­ves­ti­ga­tor and col­lab­o­ra­tor in­ter­est in our pro­grams, da­ta read­outs from the BDC-1001 monother­a­py and com­bi­na­tion dose-es­ca­la­tion stud­ies on the hori­zon as well as the ad­vance­ment of BDC-3042 through IND-en­abling ac­tiv­i­ties,” Bolt CEO Ran­dall Schatz­man added.

The com­pa­ny re­port­ed $1.4 mil­lion in rev­enue for this quar­ter — a re­sult of col­lab­o­ra­tions with Gen­mab and In­novent Bi­o­log­ics — com­pared to $0 from the same pe­ri­od in 2021. Bolt had $223.6 mil­lion as of June 30.

*A cor­rec­tion has been made to clar­i­fy that BDC-3042 is a myeloid mod­u­lat­ing ag­o­nist an­ti­body in de­vel­op­ment for sol­id tu­mors, not an im­mune-stim­u­lat­ing an­ti­body con­ju­gate (ISAC)

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

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.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

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.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

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?’”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.