Insmed Additional Positive Data from Phase 3 Bronchiectasis Study

  Insmed Incorporated (Nasdaq: INSM), a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases, today announced that additional positive results from the ASPEN study, a global, randomized, double-blind, placebo-controlled Phase 3 study to assess the efficacy, safety, and tolerability of brensocatib in patients with non-cystic fibrosis bronchiectasis, will be presented tomorrow, July 4, 2024, at the 7th World Bronchiectasis Conference (WBC) in Dundee, Scotland. Slides from this presentation can be found here.

As previously announced, the ASPEN study met its primary endpoint, with both dosage strengths of brensocatib achieving statistical and clinical significance for the reduction in the annualized rate of pulmonary exacerbations (PEs) versus placebo over the 52-week treatment period. The annualized rate of exacerbations was 1.015 for the brensocatib 10 mg group, 1.036 for the brensocatib 25 mg group, and 1.286 for placebo, representing a 21.1% risk reduction from placebo for the brensocatib 10 mg group (p=0.0019) and a 19.4% risk reduction for the 25 mg group (p=0.0046). Both dosage strengths of brensocatib also met several secondary endpoints, including significantly prolonging the time to first exacerbation and significantly increasing the odds of remaining exacerbation-free over the treatment period.

https://www.prnewswire.com/news-releases/additional-positive-data-from-pivotal-aspen-study-of-brensocatib-in-patients-with-bronchiectasis-to-be-presented-at-the-7th-world-bronchiectasis-conference-302188927.html

Ukraine not ready to compromise with Russia, says Zelenskiy aide

 Ukraine is not ready to compromise with Russia and give up any territory to end the war, a senior Ukrainian official said on Tuesday when asked about U.S. presidential candidate Donald Trump's declaration that he could quickly end the conflict.

Ukrainian President Volodymyr Zelenskiy's chief of staff, Andriy Yermak, told reporters during a visit to Washington that Kyiv would listen to any advice on how to achieve a "just peace" in the war. Russia invaded Ukraine in February 2022.

"But we (are) not ready to go to the compromise for the very important things and values ... independence, freedom, democracy, territorial integrity, sovereignty," he said.

Yermak's visit came ahead of next week's NATO summit in the U.S. capital, where Ukraine is expected to be the main topic of discussion.

Trump, the Republican nominee challenging President Joe Biden, said during a debate between the pair last week that if he is re-elected in November he would quickly solve the war in Ukraine before taking office in January.

He has not offered details of how he would do that, but Reuters reported last week that two key advisers to Trump had presented him with a plan that would involve threatening to cut U.S. assistance if Kyiv did not enter negotiations with Moscow.

Trump said during the debate, however, that he does not accept Russian President Vladimir Putin's terms. Putin has said Russia would end the war if Kyiv agreed to hand over the four regions in the east and south of the country claimed by Moscow.

Asked how Ukraine assesses that Trump would handle the war, Yermak said: "Honest answer: I don't know. Let's see."

Ukraine would lobby a new U.S. administration to continue providing it support, he said, adding that Ukraine had received bipartisan support in Washington and polling showed most Americans still support Ukraine after two years of war.

"It will be ... a decision of the American people. We will respect this choice," Yermak said of the Nov. 5 presidential election.

The United States has provided Ukraine with more than $50 billion worth of military aid since 2022. Defense Secretary Lloyd Austin said on Tuesday the U.S. will soon announce more than $2.3 billion in new security assistance for Ukraine.

https://www.yahoo.com/news/ukraine-not-ready-compromise-russia-020335508.html

AN2 upped to Outperform from Market Perform by Leerink

 Target $5

https://finviz.com/quote.ashx?t=ANTX&p=d

BIOSECURE Act Erodes Industry Confidence in Chinese Contractors: Report

While it remains to be seen if or when the BIOSECURE Act will become law, the proposed legislation has already impacted the biopharma industry’s confidence in Chinese firms, according to a recent survey by consultancy LEK.

According to Tuesday’s report, the confidence of U.S.-based life science companies in working with Chinese firms tanked by 30% to 50% in the months after the bill was introduced in Congress. LEK conducted its survey from May 24 to June 7, 2024, after the House Oversight Committee approved a draft of the BIOSECURE Act but before it was excluded from proposed amendments to the National Defense Authorization Act spending bill for fiscal year 2025.

Introduced in January 2024 by Reps. Mike Gallaghher (R-Wis.) and Raja Krishnamoorthi (D-Ill.), the BIOSECURE Act is meant to keep taxpayer dollars away from “foreign adversary biotech companies” which pose national security threats to the U.S. In May 2024, lawmakers introduced an amended bill with a grandfather clause that would allow existing contracts with Chinese firms until Jan. 1, 2032.

LEK expects contract development and manufacturing organizations—those involved primarily in manufacturing drug substances, as well as the innovation and development activities that typically take place before production—to be the hardest hit.

Biopharma companies are already starting to adjust their activities, with 68% of survey respondents saying that they have implemented interventions such as boosting compliance and legal requirements, planning to diversify suppliers and adding layers of background checks for existing partners.

While the BIOSECURE Act has named only five companies so far—WuXi Apptec, WuXi Biologics, Beijing Genomics Institute, MGI and Complete Genomics—26% of life science respondents indicated plans to shift away from their current Chinese suppliers. Still, only 2% have so far taken concrete steps toward this end, according to LEK.

Nevertheless, despite the increasingly fraught relationship between China and the U.S., several companies find the Chinese market to be an attractive opportunity and are still keen to collaborate on commercialization. A substantial proportion of respondents—around 30%—also remain open to clinical development partnerships, particularly over the next three years.

Outside the U.S., the BIOSECURE Act has also eroded industry confidence in Chinese companies, though to a much lesser extent, according to LEK. Conversely, the bill could represent a promising opportunity to service providers from Japan and Korea who are rising to meet the new demand in third-party manufacturers from other countries.

https://www.biospace.com/article/biosecure-act-erodes-industry-confidence-in-chinese-contractors-report/

Taysha Shares Positive Rett Results in Bid to Move Past Roadblocks

 Taysha Gene Therapies touted positive early-stage data last month for its gene therapy to treat Rett syndrome, which has become the company’s main focus after cutting other programs and laying off 35% of its staff. If successful, the candidate for Rett syndrome has the capability to put Taysha in a billion-dollar market.

The early-stage data only show the results of four Rett patients from a Phase I/II trial on Taysha’s AAV9 gene transfer therapy TSHA-102, however. Taysha’s focus on Rett comes after a patient death was recorded in 2022 for its experimental gene therapy for Sandhoff and Tay-Sachs diseases. While the death was not attributed to the therapy itself, it still drove down the company’s stock price, and eventually, Taysha abandoned the program, throwing its resources into Rett.

If TSHA-102 does go the distance, the market could be a lucrative play for the Dallas-based biotech. With an estimated 16,600 to 25,800 patients in the U.S., the market totals an estimated $2.5 billion, according to an analyst report from Bank of Montreal Capital Markets. If everything goes according to plan, Taysha may have a solid opportunity to carve out a good slice of the Rett market—to the tune of around $1 billion at peak revenues in 2035, experts told BioSpace.

“There’s a clear need for something better that could give these patients a real chance at having a more normal life,” said Maury Raycroft, an equity analyst at Jefferies.

Taysha’s Push in Rett Syndrome

After the patient death in 2022, Taysha announced it would focus on targeting Rett and giant axonal neuropathy (GAN) but pause work on its other R&D efforts, and axed 35% of its workforce. In 2023, further setbacks hit Taysha as the FDA requested more patient dosing to support a Biological License Application for its GAN therapy, TSHA-120.

Finally, after a Type C meeting later that year, the company chose to halt all development of TSHA-120 and focus entirely on TSHA-102.

The trial data reported in June was split into two cohorts. The pediatric patients showed improvements in motor skills, communication, and a reduction in the rates of seizure, among other observations. The adults in the trial had similar results, with one patient having normal sleep for the first time in 20 years. No serious adverse events occurred during the trial, according to Taysha.

However, the results are not only early stage but involve a very small number of patients, Raycroft reminded BioSpace. In addition, investors’ feedback noted that the scales Taysha used did not show “clear trends” or clear consistency. Raycroft said that these scales are based on caregiver and clinician assessments, however, and he puts more weight on the clinicians’ findings. He sees this as a positive start for Taysha and believes that higher dose data should be available in the year’s second half. “I think the adult data is potentially even more meaningful, based on this update, because we’re seeing data after one year for one patient, and then half the year for the other patient, and both of those patients seem durable, at a minimum.”

The Future for Taysha

For smaller biotechs like Taysha, culling programs and eliminating employees may be necessary to preserve capital to get a product on the market, Raycroft said. He noted that the Rett candidate is Taysha’s best opportunity to get a product across the finish line, and it ultimately makes sense to prioritize and focus on it.

He noted that Reata Therapeutics made a similar play with Friedreich’s ataxia drug Skyclarys, which was approved by the FDA last year and eventually acquired by Biogen. The company previously discontinued other programs in its pipeline, including its candidate for chronic kidney disease, choosing to focus solely on getting Skyclarys across the finish line.

With its recent results, Taysha is looking to net more funds, recently announcing a public offering of over 14 million shares, which the company expects to bring around $75 million. In SEC documents, Taysha highlighted that the funds from the public offering would go toward the clinical, regulatory and manufacturing development of TSHA-102.  

With Taysha, Raycroft said, “they’re focused on reducing their expenses. And making sure that every dollar they spend will be more relevant to advancing this Rett syndrome program because this is their best option at reaching that pinnacle.”

https://www.biospace.com/article/taysha-shares-positive-rett-results-in-bid-to-move-past-roadblocks/

J&J, Legend’s Phase III Win Cements Carvykti as Earlier-Line Multiple Myeloma Treatment

 Johnson & Johnson and Legend Biotech on Tuesday released interim results from the Phase III CARTITUDE-4 study, touting significant survival improvement in multiple myeloma patients after treatment with their CAR-T therapy Carvykti (ciltacabtagene autoleucel).

The partners did not provide specific data from the second prespecified interim analysis of CARTITUDE-4, only announcing that Carvykti treatment led to a “statistically significant and clinically meaningful improvement” in overall survival, compared with standard therapies. The Phase III study also found that Carvykti’s safety profile in this setting was consistent with its approved label.

Jordan Schecter, disease area leader of multiple myeloma at J&J Innovative Medicine, said in a statement that with these findings Carvykti has become “the first cell therapy to significantly improve overall versus standard of care for patients with multiple myeloma as early as second line.”

J&J and Legend will present findings from CARTITUDE-4 at an upcoming medical congress and will share them with global regulatory authorities.

Carvykti is a genetically modified autologous T-cell immunotherapy that targets the BCMA protein, which is typically expressed by multiple myeloma cells. This mechanism of action allows Carvykti to direct T-cells to BCMA-positive cells and activate their anti-cancer activity. The CAR-T therapy won its first FDA approval in February 2022 for the treatment of patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy.

In April 2024, the regulator expanded its label for use in patients who had undergone at least one prior treatment. The supplemental approval was backed by progression-free survival data from CARTITUDE-4, which showed that Carvykti reduced the risk of disease progression or death by 74% versus standard of care. These findings were published in June 2023 in The New England Journal of Medicine.

Carvykti, along with other CAR-T therapies, has in recent months been at the center of an FDA safety probe. The regulator announced in November 2023 that it was looking into reports of secondary malignancies in patients treated with CAR-T treatments. In April 2024, the FDA required manufacturers of these therapies to reflect the risk of secondary cancers in their products’ boxed warnings.

Last month, findings from a Stanford study published in The New England Journal of Medicine showed that such risk of secondary malignancies was very low.

Of 724 patients who had undergone CAR-T treatment at Stanford Health Care between 2016 and 2024, only 6.5% developed secondary cancers over a median follow-up of three years. One patient died from a secondary malignancy, though this was more likely due to the immunosuppression associated with CAR-T treatments rather than a wrong insertion of the gene in the CAR construct, according to Stanford researchers.

https://www.biospace.com/article/j-and-j-legend-s-phase-iii-win-cements-carvykti-as-earlier-line-multiple-myeloma-treatment/

'Michelle Obama only Democrat to beat Trump in new poll'

 Former first lady Michelle Obama is the only Democrat to beat former President Trump in a new poll Tuesday.

The survey, conducted by Reuters/Ipsos, found Obama was the only Democrat with a lead on Trump in a hypothetical match-up, garnering 50 percent support to his 39 percent. Only 4 percent of respondents said they would not vote at all.

Meanwhile, the poll found, President Biden and Trump are neck and neck in a head-to-head match-up. They each received 40 percent of the vote, while 8 percent said they would vote for someone else, and another 8 percent said they would not vote.

Obama was the top choice among Democrats to replace Biden on the 2024 ticket, according to a Rasmussen Reports poll released in February. Despite her popularity, the former first lady has repeatedly said she will not be pursuing a bid for the White House.

The poll comes after a rocky debate performance from Biden last week, where he appeared to stumble over his words and lacked energy. The poor showing has prompted some Democrats to call for him to step down from the ballot and make room for someone else take the reins.

Other Democrats floated as potential replacements to Biden in the poll included Vice President Harris, who received 42 percent in a head-to-head match-up with Trump, who received 43 percent. California Gov. Gavin Newsom (D) trailed Trump by 3 percentage points, and Michigan Gov. Gretchen Whitmer (D) trailed by 5 points in a hypothetical contest with the presumptive GOP nominee.

While the Reuters/Ipsos poll does not show Biden losing ground to Trump, other postdebate polls have showed that he is. The survey did find, however, that about 1 in 3 Democrats believe Biden should drop out of the race.

The White House and the Biden campaign have tried to quell concerns about the debate performance in recent days and have dismissed the calls for the president to suspend his campaign.

The poll was conducted online July 1-2 among 1,070 U.S. adults and has a margin of error of plus or minus 3.2 percentage points.

https://thehill.com/homenews/campaign/4753294-michelle-obama-donald-trump-joe-biden-democrat-2024-hypothetical-matchup-survey/