Ocugen Positive Data and Safety Review Enrollment in Phase 1/2 ArMaDa Study for Geographic Atrophy

 

• Established Low Dose as Safe and Tolerable Dose in Current OCU410 Clinical Trial
• DSMB Approval to Proceed with Medium Dose Cohort Dosing

Ocugen, Inc. (Ocugen or the Company) (NASDAQ: OCGN), a biotechnology company focused on discovering, developing, and commercializing novel gene and cell therapies and vaccines, today announced that the Data and Safety Monitoring Board (DSMB) for the Phase 1/2 ArMaDa clinical trial for OCU410 recently convened and approved to proceed dosing with the medium dose of OCU410 in the dose-escalation phase of the study.

https://www.biospace.com/article/releases/ocugen-announces-positive-data-and-safety-monitoring-board-review-and-initiation-of-enrollment-in-medium-dose-for-ocu410-a-modifier-gene-therapy-in-phase-1-2-armada-study-for-geographic-atrophy/

Novartis to File for Pluvicto Label Expansion After Promising Phase III Data

Novartis on Thursday announced that it plans to file for a label expansion for its radioligand therapy Pluvicto (lutetium-177 vipivotide tetraxetan) later this year, proposing to use the prostate cancer treatment in patients who have not yet undergone chemotherapy.

The announcement follows additional data from the Phase III PSMAfore study, demonstrating overall survival (OS) data that leaned in favor of Pluvicto.

Novartis did not provide specific data in its brief announcement, only revealing that “a pre-planned analysis at approximately 75% information fraction demonstrates an OS hazard ratio less than 1.0” in PSMAfore’s intent-to-treat population, without adjusting for cross-over.

Pluvicto’s safety profile in the interim analysis remains consistent with what had been previously disclosed in prior readouts, according to the announcement. Novartis will present full findings from PSMAfore at an upcoming medical meeting.

Designed to be intravenously administered, Pluvicto is a targeted radioligand therapeutic that works by seeking out the PSMA protein, which is typically found on prostate cancer cells. According to its label, Pluvicto’s active moiety is the radionucleotide lutetium-177, the beta-emissions from which damage the PSMA-positive cancer cells, induce DNA damage and trigger cell death.

The FDA signed off on Pluvicto in March 2022, allowing its use in adult patients with metastatic castration-resistant prostate cancer who are positive for the PSMA protein. Currently, Pluvicto can only be administered to those who have been exposed to an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy.

Using data from the PSMAfore study, Novartis is seeking to push Pluvicto up into an earlier line of treatment, before taxane therapies.

However, in October 2023, the pharma reported that the trial’s OS data were “confounded” by a strong cross-over effect—84% of patients who discontinued ARPI treatment due to radiographic progression transitioned to the Pluvicto arm. Adjusting for cross-overs pointed to a non-significant advantage for Pluvicto, though placebo was better in the unadjusted analysis.

Still, PSMAfore met its primary endpoint. The risk of radiographic progression-free survival was 59% lower in the Pluvicto group, compared with simply switching to another ARPI therapy. The radioligand therapy also improved patients’ quality of life, delayed the worsening of their pain and lowered prostate-specific antigen levels.

If its label expansion is approved, earlier Pluvicto treatment may help patients avoid the toxic side effects of chemotherapy—and may open a larger market for the targeted treatment.

https://www.biospace.com/article/novartis-to-file-for-pluvicto-label-expansion-after-promising-phase-iii-data/

US National Security, China and Biotechnology in 2024

 If it hasn’t become painfully obvious yet with the BIOSECURE Act in the news, China is aggressively pursuing a strategy to become the world’s leader in biotechnology, which poses a significant threat to U.S. national security. In recent months, members of Congress and U.S. intelligence officials have warned that Chinese biotech companies may be collaborating with Beijing, with the latest example being Wuxi AppTec, a China-based biotech reported to have allegedly transferred a U.S. client’s intellectual property (IP) to the Chinese government without consent.

In its annual threat assessment in February 2024, the Office of the Director of National Intelligence (ODNI) warned that Beijing is prioritizing biotech and is trying to fast track its science and technology development through intellectual property (IP) theft and other means for economic, political and military advantage.

“China now rivals the United States in DNA-sequencing equipment and some foundational research. Beijing’s large volume of genetic data potentially positions it to lead in precision medicine and agricultural biotechnology applications,” according to the ODNI.

Last month, the National Security Commission on Emerging Biotechnology (NSCEB) issued a white paper laying out policy options for the federal government, including requiring the president to conduct a competitive analysis of the state of biotech infrastructure and technological advancement in the U.S. compared to its strategic adversaries.

“If the United States does not lead, others will, and we risk a future in which biotechnology undermines, rather than supports, U.S. national security. The People’s Republic of China intends to win the age of biology and is making significant investments and shrewd policy decisions with the intent to outpace the United States,” warned the NSCEB.

John Crowley, the new CEO of the industry lobby Biotechnology Innovation Organization (BIO), in an opinion piece in STAT News on Thursday made a similar case that the U.S. must maintain its biotech dominance in the interest of national security.

“The country must never be at risk of losing access to safe and effective medicines. That’s why BIO, the organization I lead, supports the BIOSECURE Act, which is aimed at securing America’s domestic biomanufacturing supply chain,” Crowley wrote. “We also announced [March 13] that WuXi AppTec, one of the Chinese companies regulated by the bill, would be ending its relationship with us.”

What a difference a week makes! Just last month, BIO said it didn’t support the BIOSECURE Act. Then in a March 5 letter to Attorney General Merrick Garland, Rep. Mike Gallagher (R-Wisc.), chair of the House Select Committee on the Chinese Communist Party, requested that the Department of Justice investigate lobbying by BIO on behalf of WuXi and against the BIOSECURE Act—actions that would raise “concerns that [BIO] is operating as an unregistered agent of a foreign principal while advancing the interests of the People’s Republic of China government.”

BIO’s about-face on WuXi and the BIOSECURE Act is mind-boggling. It certainly begs the question why it took a showdown with a member of Congress for BIO to support the BIOSECURE Act and for the lobbying group to part ways with WuXi.

Other Companies in Crosshairs

The BIOSECURE Act specifically names the BGI Group, MGI, Complete Genomics and WuXi, and it isn’t the only congressional bill targeting these companies. In the Senate, the Prohibiting Foreign Access to American Genetic Information Act of 2024 also seeks to implement a fast-track ban applied to the same four firms, as well as their subsidiaries, from receiving U.S. taxpayer dollars through federal contracts, grants and loans.

“The U.S. intelligence community has cited the Chinese Communist Party’s concerted efforts to acquire human genetic and related data through biotechnology companies, such as the BGI Group, as a serious threat to U.S. national security,” according to Senators Gary Peters (D-Mich.) and Bill Hagerty (R-Tenn.), who authored the legislation.

And the list of targeted Chinese biotech companies continues to grow. In the House of Representatives, Gallagher and Rep. Raja Krishnamoorthi (D-Ill.) wrote a March 29 letter to Defense Secretary Lloyd Austin urging the Department of Defense to add seven Chinese biotechs to DoD’s 1260H list of “problematic People’s Republic of China” companies, including Innomics, STOmics, Origincell, Vazyme Biotech and Axbio.

How will a crackdown on WuXi and other Chinese biotechs affect U.S.-based biopharma companies? Merck, Iovance Biotherapeutics and Kyverna Therapeutics have detailed interactions with the SEC about potential impacts on their future programs. A Kyverna spokesperson in an email statement to BioSpace said it is aware of the “ongoing concerns related to the BIOSECURE Act” and is “closely monitoring the developments.”

If that weren’t enough, another area of collaboration that could suffer from these high-profile tensions between the U.S. and China is in the hot area of antibody-drug conjugate (ADC) technology. However, Jake Van Naarden, president of Eli Lilly’s Loxo Oncology division, told BioSpace that nearly all major pharma companies have contract relationships in China and cautioned against “[throwing] the baby out with the bathwater” by shutting down cooperation on ADC and other drug development. Hopefully, cooler heads will prevail.   

https://www.biospace.com/article/year-of-the-dragon-us-national-security-china-and-biotechnology-in-2024-/

FTC Will Have More Time to Review Novo’s $16.5B Catalent Buy

 The Federal Trade Commission and the U.S. Department of Justice antitrust division have an additional 30 days to review the Novo Nordisk Foundation’s $16.5 billion acquisition of contract manufacturer Catalent, according to an SEC filing on Wednesday.  

Catalent’s filing detailed that the Novo Nordisk Foundation, the parent company of Novo Holdings, had filed their corresponding forms with the FTC and the DOJ’s antitrust division. However, after “informal discussions” with the FTC, the Novo Nordisk Foundation decided to withdraw and refile their submission.

According to Catalent, this new filing will give the FTC and the antitrust division more time to review the transactions. If a second request is issued, the agencies could extend the review period by 30 additional days.

BioSpace reached out to the Novo Nordisk Foundation for comment but did not get a response. Catalent declined to comment.

The FTC and the DOJ have been changing their approach to mergers and acquisitions with the development of draft guidelines last year. The guidelines consider how companies would leverage negotiating power along with 13 other factors for reviewing M&A.

Novo Holdings, which also acts as the investment arm of the Novo Nordisk Foundation, announced the Catalent’s purchase in February, aiming to complete the deal sometime toward the end of 2024.

Novo Nordisk will purchase three of Catalent’s sterile fill finish sites, one in the U.S. and two in Europe, for $11 billion upfront. The move is designed to help increase the production capacity of its blockbuster semaglutide products, such as Ozempic and Wegovy.

However, Catalent’s existing contracts with pharma customers has been raised by Novo’s competitors as an area of concern for the acquisition. While experts expect that the contracts in place at the three Catalent facilities will not be affected, Eli Lilly CFO Anat Ashkenazi said on an earnings call in February that Catalent is an “integral part” of its commercial and pipeline products and vowed to hold the manufacturer accountable for its contract.

https://www.biospace.com/article/ftc-will-have-more-time-to-review-novo-s-16-5b-catalent-buy/

Contineum Dials Back Plans with $110M IPO to Fund Neuroinflammatory Trials

 Contineum Therapeutics went public on Friday, trading on the Nasdaq Global Select Market under the ticker symbol CTNM and dialing back its expectations to raise $110 million for clinical trials of a challenger to Boehringer Ingelheim and Roche.

The San Diego-based biotech filed to go public in March 2024 to fund development of two clinical-phase candidates. Johnson & Johnson paid $50 million upfront for one of the assets, PIPE-307, in April 2023 but Contineum still needs to fund a Phase II trial in relapsing-remitting multiple sclerosis (MS). The biotech also wants cash to trial its wholly owned idiopathic pulmonary fibrosis (IPF) and MS prospect, PIPE-791.

Earlier this week, Contineum set out plans to sell 8.8 million shares for $16 to $18 a piece. The biotech downgraded its target to secure its transition on to the Nasdaq, ultimately agreeing to sell almost 6.9 million shares for $16 each. Contineum expects gross proceeds of around $110 million, before deducting underwriting discounts and commissions and other offering expenses.

The company is planning to spend around $66 million on the development of PIPE-791. The candidate is an oral small molecule inhibitor of LPA1, a receptor implicated in scarring in the lung disease IPF and the promotion of neuroinflammation in MS. Studies also suggest LPA1 may limit remyelination, the holy grail of MS outcomes. Drug developers have tried for decades to promote remyelination, without success.

Contineum is planning Phase II trials of PIPE-791 in IPF and progressive MS. Boehringer Ingelheim’s Ofev and Roche’s Esbriet currently compete for the IPF market. Preclinical studies and a Phase I trial suggest PIPE-791 may have a convenience advantage. Contineum plans to study once-daily doses of PIPE-791, whereas Ofev and Esbriet are respectively taken two and three times a day.

The biotech is part of a clutch of drug developers that want to treat IPF by targeting LPA1. Bristol Myers Squibb shared Phase II data on a LPA1 antagonist in 2023, more than a decade after entering the space through the $325 million acquisition of Amira Pharmaceuticals. Contineum founder and chief scientific officer Daniel Lorrain used to work at Amira.

Other companies are racing BMS to market. Amgen’s acquisition of Horizon Therapeutics included a Phase II LPA1 drug candidate. AbbVie joined the fray by buying DJS Antibodies for $255 million in 2022.

Contineum’s exploration of LPA1 in progressive MS sets it apart from the competition. The biotech said PIPE-791 is the only brain-penetrant LPA1 receptor antagonist in clinical development progressive MS, an indication that has thwarted other companies.

The IPO will also support the Phase II trial of PIPE-307 that got underway last year. Contineum agreed to complete the study of the M1R inhibitor in relapsing-remitting MS when J&J struck a deal for the asset. The biotech has earmarked $16.2 million from the IPO haul for the study. Contineum contends inhibition of M1R may directly promote remyelination.

Contineum’s listing on the Nasdaq makes it part of the resurgence of IPOs seen in the first few months of this year. Like many other members of the class of 2024, the biotech has advanced deeper into the clinic before going public than the early-stage biotechs that listed during the IPO peak of 2021.

https://www.biospace.com/article/contineum-dials-back-plans-with-110m-ipo-to-fund-neuroinflammatory-trials/

AstraZeneca’s Imfinzi Clinches Late-Stage Victory in Aggressive Lung Cancer

 AstraZeneca on Friday announced that its PD-L1 blocker Imfinzi (durvalumab) met its primary efficacy endpoints in the Phase III ADRIATIC study, showing that it can significantly improve survival in patients with limited-stage small cell lung cancer.

The pharma did not disclose specific figures in its announcement, only revealing that Imfinzi elicited a “statistically significant and clinically meaningful improvement” in the ADRIATIC’s dual primary endpoints of overall survival and progression-free survival (PFS).

In terms of safety, Imfinzi’s adverse event profile in ADRIATIC was consistent with what had been established in prior studies. No new signals of concern were detected.

Susan Galbraith, executive vice president of oncology R&D at AstraZeneca, in a statement called ADRIATIC’s results “exciting,” adding that they further establish the “transformative efficacy” of Imfinzi as a treatment for patients with extensive-stage small cell lung cancer (SCLC).

The data also point to the potential of providing a “curative-intent immunotherapy treatment to this earlier-stage setting of small cell lung cancer for the first time,” Galbraith added. AstraZeneca will present full data and findings from ADRIATIC at an upcoming medical congress and will submit them to regulatory authorities worldwide.

Afflicting around 15% of all lung cancer patients, SCLC is a relatively uncommon form of lung cancer but is generally aggressive and often recurs after treatment. According to the Cleveland Clinic, if left untreated, most patients die within months of SCLC diagnosis and less than 10% of patients survive beyond five years.

Imfinzi, a human monoclonal antibody, addresses SCLC by preventing the interaction of PD-L1 with the PD-1 and CD80 proteins. This mechanism of action allows Imfinzi to block a tumor’s ability to evade and dampen the immune system, while also boosting the body’s anti-cancer immune response.

The FDA first approved Imfinzi in 2017 for the treatment of advanced bladder cancer and the antibody has picked up several indications since. Imfinzi entered the lung cancer space in 2018, when it won the regulator’s nod for unresectable stage III non-small cell lung cancer. In March 2020, the FDA approved Imfinzi for extensive-stage SCLC.

Friday’s readout follows disappointing data from the Phase III PACIFIC-2 study, posted in November 2023. Unlike ADRIATIC, PACIFIC-2 focused on the more common but less aggressive non-small cell lung cancer and administered Imfinzi alongside chemoradiotherapy. The combination regimen did not significantly improve PFS in patients with unresectable stage III NSCLC and triggered a higher risk of infections, compared with chemoradiotherapy alone.

AstraZeneca is running several other studies under the PACIFIC clinical development program, seeking to push Imfinzi into earlier lines of lung cancer treatment.

https://www.biospace.com/article/astrazeneca-s-imfinzi-clinches-late-stage-victory-in-aggressive-lung-cancer/

Diddy Former Bodyguard Claims Music Mogul Had Tapes Of "Politicians" And "Princes"

 by Paul Joseph Watson via Modernity.news,

The former bodyguard of Sean ‘Diddy’ Combs’ claims the music mogul had blackmail tapes of politicians, princes and other prominent individuals who were involved in his sex parties.

Combs, who has been hit with a barrage of physical abuse, rape and sexual trafficking allegations, had his homes in Miami and Los Angeles raided by the Department of Homeland Security last month, during which federal agents seized computers and other electronic devices.

Gene Deal, who was present the night when Notorious B.I.G. was fatally shot in 1997, made the sensational comments during an interview with ‘The Art of Dialogue’ YouTube channel.

“I don’t think it’s only celebrities gonna be shook. He had politicians in there, he had princes in there. He also had a couple of preachers in there,” said Deal.

“Can you imagine, he had every room bugged,” he added.

When asked why Combs’ media department had stayed silent on the allegations against him, Deal responded, “Either they took part in some of the stuff that happened, or they’re scared that it may mess up their brand.”

Fox News host Jesse Watters speculated that the tapes, if they exist, are now in the hands of the feds and “that’s a lot of blackmail.”

Deal’s comments echo those of rapper Rodney ‘Lil Rod’ Jones, who claimed Combs had hidden cameras throughout his home to record sex tapes involving celebrities during his “freak off” parties.

Combs has denied all the allegations against him and hasn’t been hit with any criminal charges as of yet.

https://www.zerohedge.com/political/sean-diddy-combs-former-bodyguard-claims-music-mogul-had-tapes-politicians-and-princes