BridgeBio spinout launches with $200M for KRAS cancer drugs

 

• A group of well-known biotechnology investors is putting $200 million into a newly launched spinout of BridgeBio Pharma developing drugs that target two common cancer genes.

• BridgeBio Oncology Therapeutics, which was previously organized as a BridgeBio subsidiary called TheRas, will advance three drug candidates. Two aim at cancers driven to growth by mutations in a gene called KRAS, while the other blocks signaling between two proteins often involved in tumor development.

• Comorant Asset Management led the financing, along with Omega Funds. Nine other venture firms participated, including Deerfield Management and GV.

Up until not that long ago, BridgeBio Oncology Therapeutics would have had a more difficult pitch to investors.

Cancer drug researchers for decades had sought to pin down the oncogene KRAS, errors in which were identified as common catalysts for tumors of the lungs, colon and pancreas. Their efforts were universally unsuccessful, earning KRAS a reputation as “undruggable.”

A 2013 paper by scientists at the University of California, San Francisco, helped crack the code, suggesting how to target with drugs a “pocket” on a certain kind of mutated KRAS protein. Their work led to a new wave of drug development, one which eventually produced Amgen’s Lumakras, approved in the U.S. in 2021, and Mirati Therapeutics’ Krazati, cleared the following year.

With those drugs available, BridgeBio Oncology Therapeutics doesn’t need to convince anyone that drugging KRAS is possible. Instead, its pitch centers on how to build a better KRAS drug.

Its most advanced candidate is designed, like Lumakras and Krazati, to bind to a type of mutated KRAS protein to shut down the growth signals that swell tumors. Unlike Lumakras and Krazati, the candidate, dubbed BB-8520, can bind to the protein in its active state, as well as when its inactive. (Lumakras and Krazati binding to inactive KRAS prevents the protein from cycling back on.)

“We actually inhibit the protein that signals, the active protein,” said Eli Wallace, BridgeBio Oncology Therapeutics’ CEO. “Really what’s driving the tumor is that on stage.”

Wallace noted, too, how the most common resistance mechanisms to the current KRAS inhibitors involve increased time in the active stage.

BB-8520 is already in clinical testing, with a Phase 1 study of people with lung cancer underway this month.

It has company, however. Frontier Medicines recently raised $80 million to fund, in part, development of a drug that also targets the on and off states of the KRAS protein.

https://finance.yahoo.com/m/96563773-04c8-3a5b-93ae-2b0076a45785/bridgebio-spinout-launches.html

Arbutus results, update

 End-of-treatment data from two Phase 2a combination clinical trials with imdusiran to be presented at the EASL Congress in June 2024

Preliminary data from the single-dose portion of the AB-101-001 clinical trial show that AB-101 was generally well-tolerated and bound to the receptor target in healthy subjects

Court provides claim construction ruling in ongoing patent infringement lawsuit against Moderna; Court date scheduled for April 21, 2025

Strong financial position – expected cash runway extended through the second quarter of 2026

Conference Call and Webcast Today at 8:45 AM ET

Arbutus will hold a conference call and webcast today, Thursday, May 2, 2024, at 8:45 AM Eastern Time to provide a corporate update. To dial-in for the conference call by phone, please register using the following link: Registration Link. A live webcast of the conference call can be accessed through the Investors section of Arbutus' website at www.arbutusbio.com.  

An archived webcast will be available on the Arbutus website after the event.

https://www.biospace.com/article/releases/arbutus-reports-first-quarter-2024-financial-results-and-provides-corporate-update/

Astellas In 2nd CAR-T Agreement with Poseida to Develop ‘Convertible’ Cancer Therapies

 Astellas Pharma on Wednesday entered into a collaboration and license agreement with Poseida Therapeutics to develop novel CAR-T therapies for solid tumors.

Under the deal, Astellas will pay an upfront fee of $50 million and has pledged up to $550 million in potential development, sales and other contingent payments. Poseida will also be eligible for up to low-double digit tiered royalties on net sales. Astellas will conduct the transaction through its subsidiary Xyphos Biosciences.

The collaboration is designed to combine “the innovative cell therapy platforms from each of the companies,” according to Wednesday’s announcement.

Poseida will contribute its proprietary allogeneic CAR-T platform, while Xyphos will lend both its ACCEL and convertibleCAR technologies. The partnership’s goal is to produce one CAR-T construct, which in turn will yield two convertibleCAR product candidates for solid tumors.

Xyphos will reimburse Poseida for costs under the agreement and will take charge of R&D activities and future commercialization of products that may arise from the partnership, according to the companies.

Designed to be a flexible cell therapy, Xyphos’ convertibleCAR technology makes use of a modified NKG2D protein, a natural human receptor that is commonly found on natural killer cells and some T-cells, and functions to facilitate immune surveillance.

According to the biotech’s website, the modifications to NKG2D allow the convertibleCAR construct to be controlled and activated with engineered molecules, such as bispecific antibodies, that can recognize binding sites on tumor cells. This approach brings tumor cells close to immune cells that have been activated to attack and destroy them.

In addition, attaching different functional moieties to the convertibleCAR construct allows them to target different antigens, which could help therapies target tumor cells that have changed to avoid detection by the immune system.

Adam Pearson, chief strategy officer at Astellas, in a statement said that the Poseida partnership “will bring synergies between the two companies’ breakthrough research and will ultimately lead to the expansion of Astellas’ portfolio and to the delivery of innovative CAR-T cell therapies to cancer patients.”

Wednesday’s announcement follows a previous agreement between the two companies, inked in August 2023, to support Poseida’s work in cancer cell therapeutics. Astellas at the time invested $50 million in Poseida, half of which was used to acquire 8.8% of Poseida’s shares, while the other half bought the right of exclusive negotiation and first refusal to license the clinical-stage CAR-T program P-MUC1C-ALLO1 for solid tumors.

https://www.biospace.com/article/astellas-inks-second-car-t-agreement-with-poseida-to-develop-convertible-cancer-therapies/

Moderna Walks Away from Potential $3B Gene Editing Deal with Metagenomi

 Moderna has backed out of its gene editing deal with Metagenomi, handing back full global rights to the primary hyperoxaluria type 1 program and other related technologies, including base editors and RNA-mediated integration systems.

Metagenomi in Wednesday’s announcement said that the partners have “mutually agreed” to terminate the agreement, but that the decision came after a “strategic prioritization” by Moderna. However, the mRNA-focused biopharma company will remain a shareholder of Metagenomi.

Despite losing a powerhouse partner, Metagenomi CEO Brian Thomas said in a statement that the biotech is “pleased to regain full control of the development of base editing technology” and its RNA-mediated integration systems (RIGS), which will allow the company to harness these platforms to develop treatments in “areas of significant need, such as Alpha-1 antitrypsin deficiency and Wilson’s disease.”

Metagenomi is capable of advancing programs on its own, Thomas said, adding that the biotech has over the years built up its footprint and talent base, as well as “leveraged significant private and public funding to greatly expand our gene editing toolbox, and established in-house manufacturing.”

Moderna and Metagenomi inked the gene editing partnership in 2021, combining the former’s mRNA platform with the latter’s gene editing expertise to develop in vivo human therapies.

At the time, the partners did not disclose the specific financial details of the deal, though subsequent SEC filings showed that Metagenomi could have potentially generated more than $3 billion from the agreement, plus an upfront payment and royalties. As of December 31, 2023, the biotech had secured $49.6 million from the partnership.

In February 2024, Metagenomi debuted on the Nasdaq Global Select Market with a nearly $94 million initial public offering (IPO). The biotech’s shares cratered 31% the following day, highlighting the problems faced by earlier-stage companies that go public.

Some of the market’s apprehension over Metagenomi’s IPO could be attributed to the fact that it has no candidates in the clinic. Instead, the biotech has focused on creating what it brands as “the most diverse genome editing toolbox” to target various genetic conditions.

For Moderna, the discontinuation of the Metagenomi partnership comes after it suffered more than $1 billion in losses and write-downs linked to low demand for its vaccine and cancelled orders for Africa. The company has in turn suspended the construction of an mRNA manufacturing facility in Kenya while it assesses the demand for its vaccines.

https://www.biospace.com/article/moderna-walks-away-from-potential-3b-gene-editing-deal-with-metagenomi/

FDA Approval Fuels Boehringer’s Biosimilar Challenge to AbbVie’s Humira

 The FDA on Wednesday approved a high-concentration and citrate-free version of Boehringer Ingelheim’s Cyltezo (adalimumab-adbm), its interchangeable biosimilar to AbbVie’s blockbuster antirheumatic treatment Humira (adalimumab).

The high-concentration version of Cyltezo, which carries a 100-mg/mL dose of the biosimilar, comes in a pre-filled syringe or autoinjector and is sold at a 5% discount to the branded reference product. An unbranded version of Cyltezo is also available at an 81% discount to Humira. A low-concentration, 50-mg/mL version of the biosimilar has been on the market since July 2023, according to Boehringer Ingelheim.

Stephen Pagnotta, biosimilar commercial lead at Boehringer Ingelheim, in a statement said that this latest Cyltezo approval will further expand “treatment access for patients living with certain chronic inflammatory diseases.”

Approved in October 2021, Cyltezo is an interchangeable biosimilar to Humira and is indicated for all the same conditions, including moderate-to-severe rheumatoid arthritis, Crohn’s disease and ulcerative colitis. With the FDA’s interchangeability designation, Cyltezo can be used in place of Humira without needing to change the patient’s prescription.

Cyltezo is backed by data from the Phase III VOLTAIRE-X comparative clinical trial, which looked at the effects of switching between Humira and the biosimilar. The study found that Cyltezo was equivalent to Humira, leading to no meaningful clinically differences in safety, efficacy and pharmacokinetic profile.

Wednesday’s FDA approval is supported by findings from the Phase I VOLTAIRE-HCLF study, which compared the bioavailability of the high- and low-concentration formulation of Cyltezo in 200 healthy volunteers.

The approval of Cyltezo’s high-concentration, citrate-free formulation comes as biosimilars claim more market ground against AbbVie’s Humira. Earlier this month, biosimilars saw a 36% surge in prescriptions after leading pharmacy benefit manager CVS Caremark took Humira off of its major national commercial formularies.

Sandoz’s biosimilar Hyrimoz (adalimumab-adaz)—which is being co-developed and commercialized by the CVS Health subsidiary Cordavis—accounted for more than 93% of the biosimilar growth. In the week ending April 5, 2024, there were nearly 8,300 new prescriptions for Hyrimoz, compared to only 640 in the week ending March 29.

In addition to Hyrimoz and Cyltezo, there are several other Humira biosimilars competing in the market, including Amgen’s Amjevita, Celltrion’s Yufly,a Alvotech and Teva’s Simlandi and Organon and Samsung Bioepis’ Hadlima.

https://www.biospace.com/article/fda-approval-fuels-boehringer-ingelheim-s-biosimilar-challenge-to-abbvie-s-humira/

'Biden Says There Are Very Fine People On Both Sides Of The Oct. 7 Debate'

  by David Harsanyi via The Epoch Times (emphasis ours),

“I condemn the anti-Semitic protests ...” President Joe Biden told reporters after days of anti-Jewish demonstrations at Columbia University and other Ivy League schools. “I also condemn those who don’t understand what’s going on with the Palestinians ...”

Any morally clearheaded American already has a very good idea of what’s going on. Biden is bothsidesing the actions of keffiyeh-wearing terror cheerleaders on Columbia’s Gaza Quad—who target American Jews who have absolutely no bearing on Israel’s actions—with those who refuse to accept the blood libel of “genocide” in Gaza. It is the kind of odious moral relativism one expects to hear from a “Squad” member or clout-chasing far-right “influencer,” not the president.

Hamas, the governing authority in an autonomous Gaza—still supported widely by the Palestinian people—flooded over the border on Oct. 7, 2023, raping, murdering, and kidnapping more than a thousand men, women, and children in Israel, including American citizens. Afterward, Hamas retreated and hid among civilians to generate as many Palestinian martyrs as possible. The Israelis retaliated against this nihilistic death cult, keeping the civilian-to-combatant casualty ratio lower than perhaps any other instance of modern urban warfare.

That’s what’s going on. But because a not-insignificant contingent on the contemporary left is now both anti-Semitic and anti-“colonialist,” the president demanded Israel stop before the job was done. And he is willing to sell out a longtime ally and forsake the lives of American hostages to try to entice the votes in Jew-hating enclaves like Dearborn, Michigan, Yale University, and The Washington Post newsroom.

A number of people have pointed out the similarities between Biden’s condemnations and former President Donald Trump’s post-Charlottesville, Virginia, march “very fine people” comment. It’s a good gotcha. After all, Biden has risibly claimed that Trump’s comments impelled him to run for president (for the third time).

There is, however, a key difference. Trump’s garbled line was almost surely not aimed at tiki-torch neo-Nazis. Believe what you like about Trump’s motivations, but he also later unequivocally condemned the white supremacists on more than one occasion. Biden, on the other hand, can’t even get himself to call out brownshirts without throwing them a bone.

Also, incidentally, unlike the nuts in Virginia, these people will be working at our top law firms, in media organizations and in the State Department. Oh, the president also wants you to pay their loans.

Earlier, The Washington Post, like most outlets, claimed that “Biden denounces antisemitism on college campuses amid Yale, Columbia protests.” While technically true, the framing ignores the president’s equivocation. The denouncement was a pro forma White House Passover press release that spent as much space prattling on about a two-state solution as it did the “protests.” For comparison, Biden’s Ramadan press release noted the “terrible suffering on the Palestinian people,” repeated fake Hamas causality numbers and condemned “Islamophobia,” but said nothing about the widespread outbreak of anti-Semitism.

Then again, Democrats are increasingly incapable of even talking about anti-Semitism without diluting any condemnation with mention of “Islamophobia.”

You might recall a few years back a certain Democratic congresswoman was going on about “Benjamin”-grubbing rootless cosmopolitans hypnotizing the world for their evil. After a handful of Jewish Democrats complained about her rhetoric, then-House Speaker Nancy Pelosi finally agreed to pass a resolution condemning Rep. Ilhan Omar. By the end of debate, of course, the resolution was teeming with platitudes and condemnations of a rainbow of thought crimes, with references to Alfred Dreyfus, Leo Frank, Henry Ford, and “anti-Muslim bigotry,” but not Omar.

“We all have a responsibility to speak out against anti-Semitism, Islamophobia, homophobia, transphobia, racism, and all forms of hatred and bigotry, especially as we see a spike in hate crimes in America,” is how Sen. Kamala Harris whitewashed the rising anti-Jewish pronouncements of her party. Which is to say, for years now, Democrats have been downplaying anti-Semitism as it creeped into college campuses, Congress, the Women’s March, Black Lives Matter, and now the mainstream.

And now, here we are. We have a president who can’t make a moral distinction between bigots and their targets.

https://www.zerohedge.com/political/joe-biden-says-there-are-very-fine-people-both-sides-oct-7-debate

UnitedHealth says hackers potentially stole a third of Americans' data

Hackers who breached UnitedHealth's tech unit in February potentially stole a third of Americans' data, the largest U.S. health insurer's CEO told a Congressional committee on Wednesday.

Two Congressional panels grilled CEO Andrew Witty about the cyberattack on the company's Change Healthcare unit, which processes around 50% of all medical claims in the U.S.

The breach has caused widespread disruptions in claims processing, impacting patients and providers across the country.

Witty fielded heated questions from Senators on the House Energy and Commerce Committee about the company's failure to prevent the breach and contain its fallout.

Pressed for details on the data compromised, Witty said "maybe a third" of Americans' protected health information and personally identifiable information was stolen.

"We continue to investigate the amount of data involved here," he added. "We do think it's going to be substantial."

The cybercriminal gang AlphV hacked into Change on Feb. 12 using stolen login credentials on an older server that did not have multi-factor authentication, Witty said.

"It was ... a platform which had only recently become part of the company was in the process of being upgraded," Witty said, referring to UnitedHealth's $13 billion acquisition of Change in 2022.

The platform also did not have the security measures prescribed in a joint alert issued by the FBI and U.S. cyber and health officials in December 2023 to specifically warn about AlphV, or BlackCat, targeting healthcare organisations.

UnitedHealth paid the gang around $22 million in bitcoin as ransom, Witty said, adding that however there was no guarantee that the breached data was secure and could not still be leaked. Another hacking group claiming to be an offshoot of AlphV said last month it had a copy of the data, though the company has not verified that claim.

The Senate Finance panel probed the outsized influence of UnitedHealth - which has a market capitalization of $445 billion and annual revenue of $372 billion - on American healthcare. But Witty said the company's problems were not a threat to the broader economy.

Senator Bill Cassidy said senators on the panel "would have to ask, is the dominant role of United too dominant because it is into everything and messing up United messes up everybody?"

"My point is, the size of United becomes a it's almost a too big to fail and sure, because if it fails, it's going to bring down far more than it ordinarily would," Cassidy said.

Witty said in response, "I don't believe it is because actually despite our size, for example, we have no hospitals in America, we do not own any drug manufacturers."

Yet, Change processes medical claims for around 900,000 physicians, 33,000 pharmacies, 5,500 hospitals and 600 laboratories in the U.S.

U.S. military members' data was also stolen in the hack, Witty revealed, without saying how many of them were impacted.

Senate Finance Committee Chairman Ron Wyden called the hack a national security threat.

"I believe the bigger the company, the bigger the responsibility to protect its systems from hackers. UHG was a big target long before it was hacked," he added.

"UnitedHealth Group has not revealed how many patients' private medical records were stolen, how many providers went without reimbursement, and how many seniors are unable to pick up their prescriptions as a result of the hack," said Wyden.

In letters to both congressional committees, the American Hospital Association said an internal survey of its members found that 94% of hospitals reported damage to cash flow, and more than half reported "significant or serious" financial damage due to Change's inability to process claims.

Similarly, 90% of respondents to an American Medical Association survey of doctors said they continue to lose revenue because of the hack, according to the group's written testimony to the Senate Finance Committee.

https://www.yahoo.com/news/unitedhealth-ceo-testifies-u-senate-132513974.html