RF Innovations’ Apex 6 Generator aligns with specifications required for Autonomix’s ablation system and facilitates ongoing development
Transaction further reinforces Autonomix’s FDA regulatory pathway
Monday, July 15, 2024
License Agreement with Humacyte to Develop BioVascular Pancreas
Pluristyx, a leading provider of tools, technologies, and services for the development of cellular therapies, is pleased to announce a license agreement with Humacyte, Inc., a clinical-stage biotechnology platform company developing universally implantable, bioengineered human tissue at commercial scale. Humacyte has licensed Pluristyx’s clinical-grade PluriBank™ induced Pluripotent Stem Cell (iPSC) line as starting materials for manufacturing insulin-producing cells for their BioVascular Pancreas (BVP™) product candidate. This partnership includes access to Pluristyx’s revolutionary panCELLa™ platform that enables the generation of “hypoimmune” cells for clinical implantation. PluriBank™ iPSCs are derived from regulatory-compliant donors, extensively characterized, and expanded and banked to provide purity, identity, and genetic integrity for patient safety, available with custom edits and Pluristyx’s proprietary FailSafe® and iACT™ edits with a goal of providing improved safety and efficacy.
Lexeo links gene therapy to improvements in rare heart disease but disappoints investors
Lexeo Therapeutics has guided its Friedreich ataxia (FA) gene therapy through an early test, generating evidence of improvements in cardiac status in early-phase trials. But the biotech ran into problems when testing the effect of the candidate on fitness and was left with a gap in evidence.
The analysis pooled data from Lexeo’s phase 1/2 study and an investigator-initiated phase 1a trial run at Weill Cornell Medicine. Lexeo struck a deal with Weill Cornell for the data in April. The studies are testing whether LX2006 can treat cardiac dysfunction in FA by increasing the expression of FXN, a protein that is involved in the function of heart muscle. Lexeo has at least six months of data on eight participants.
Four people had elevated left ventricular mass index (LVMI), a predictor of cardiac morbidity and mortality, at the start of the study. Three of those subjects experienced a more than 10% reduction in LVMI at 12 months. Lexeo also saw declines in lateral wall thickening, an early indicator of an inefficient heart, and drops in a biomarker of myocardial injury. FXN expression increased in evaluable patients.
Lexeo tried to assess LX2006’s effect on patients’ lives using V02 max, a measure of cardiorespiratory fitness. However, the researchers saw baseline peak VO2 levels were extremely low, a finding that Lexeo said likely reflects a combination of neurological impairment and reduced cardiac functional capacity.
Three of the eight participants were unable to reach the level of effort needed to reliably interpret peak VO2. Across the other five subjects, Lexeo tracked average improvements of 1% after six months and 4% after 12 months. The biotech will continue evaluating peak V02 in its studies and is looking into other cardiopulmonary exercise test measures that may be more useful in the patient population.
While the evidence supporting LX2006 comes from cardiac assessments, for now, Lexeo said there are precedents for drugs winning approval on the strength of LVMI or transgene expression. Eric Adler, chief medical officer and head of research at Lexeo, made the case for LVMI on a call with investors to discuss the data.
“It has regulatory precedent behind it, obviously we’ve seen recently, and we know specifically in FA increases in LVMI are associated with bad outcomes. A 10% increase in LVMI is associated with a 20% increased risk of death,” Adler said. “So, we have a high degree of confidence that that should be an excellent potential outcome moving forward that we should look at in our trials.”
Lexeo has moved into the third dose cohort. Nolan Townsend, CEO at Lexeo, told investors “we believe a higher dose cohort could achieve higher protein levels” and quoted preclinical data showing benefits at higher doses to make his case. The move into the higher dose is supported by the safety profile seen in the two trials, neither of which has reported any treatment-related serious adverse events.
The biotech declined to discuss the regulatory timeline on the call with investors but sees potential for accelerated approval. The belief LX2006 may benefit from accelerated approval reflects a lack of existing treatments. Reata Pharmaceuticals, which Biogen bought for $7.3 billion, won FDA approval for Skyclarys in 2023 but it only showed efficacy on neurological measures.
Lexeo’s focus on cardiac measures differentiates LX2006 from Skyclarys but the market could become more competitive in the coming years. Voyager Therapeutics and Neurocrine Biosciences are working on an FXN gene therapy. Solid Biosciences and Lacerta Therapeutics have gene therapies in the works, too, while Prime Medicine and Tune Therapeutics have early stage gene-editing programs.
Artelo OKd on Application for ART26.12, a Selective Fatty Acid Binding Protein 5 Inhibitor
ART26.12 seeks to address a critical need in painful neuropathies, including chemotherapy-induced peripheral neuropathy for which there is no FDA-approved treatment
Phase 1 trial results expected in the first half of 2025
Metagenomi CSO Steps Down Shortly After IPO, Moderna Exit
Following a disappointing IPO and the loss of Moderna’s gene editing contract, Metagenomi’s Chief Scientific Officer Luis Borges is departing the biotech.
Metagenomi Chief Scientific Officer Luis Borges has left the California-based biotech, according to a message posted on LinkedIn last week.
Borges wrote that he has “parted ways with Metagenomi by mutual agreement,” noting that his time with the company “has been incredibly valuable.” Borges spent eight months with the biotech after being appointed in November 2023. He had previously been at Cell Medica and Century Therapeutics, serving as CSO for both companies.
Metagenomi launched its bid to start trading on the Nasdaq Global Select Market during Borges’ tenure, initially aiming for an $86.9 million raise. Ultimately, the biotech put 6.25 million of its shares up for sale at $15 apiece for an initial public offering (IPO) of nearly $94 million.
The market was not impressed, however, and Metagenomi’s stocks crashed nearly 31% on the day of its debut. The biotech has recently been trading at around $5.
Metagenomi currently has no clinical-stage candidates, and its IPO highlights the difficulties preclinical biotechs may face should they seek to go public. The biotech is banking its business on what it calls “the most diverse genome editing toolbox,” which it envisions will be “capable of correcting any type of genetic mutation found anywhere in the genome.”
Despite its relatively young pipeline, Metagenomi is backed by several high-profile supporters, including Bayer, which led its $275 million Series B fundraising round in January 2023. A few months earlier, in November 2022, Metagenomi entered into a gene editing partnership with Ionis, which could potentially lead to a $3 billion haul for the biotech.
Borges’ departure comes months after Moderna backed out of its own gene editing contract with Metagenomi. In May 2024, the mRNA specialist announced that it would return full global rights to the primary hyperoxaluria type 1 program to Metagenomi, along with other base editors and RNA-mediated integration systems.
The termination was “mutually agreed” upon by the two companies, Metagenomi announced at the time, although it noted that the change was prompted by a strategic prioritization by Moderna, which will stay on as a shareholder of the biotech.
In the first quarter of 2024, Metagenomi announced that it had $327.4 million in cash, cash equivalents and marketable securities, including its IPO raise. The biotech is also preparing to nominate a development candidate for its hemophilia A program by mid-2024.
https://www.biospace.com/business/metagenomi-cso-steps-down-shortly-after-ipo-moderna-exit
Sunday, July 14, 2024
Project 2025 & The Continued Democrat Meltdown
by Richard Truesdell and Keith Lehmann via American Greatness,
Tying Donald Trump to Project 2025 is the latest desperation tactic from Democrats. But it’s likely to backfire. It might actually create a new generation of Conservatives in the process.
Last year, the Heritage Foundation published the Mandate for Leadership as assembled by a consortium of people and think tanks called Project 2025. It is a compilation of long-standing recommended Conservative policies for the next Republican administration. The Project 2025 group claims the document is “the Conservative movement’s unified effort to be ready for the next Conservative administration to govern at noon, January 20, 2025.”
It absolutely petrifies progressive Democrats.
Looking at a portion of the 900+ page compendium, we note that it contains policy suggestions that have been embedded within the Conservative platform for over sixty years. We also note that proclamations from right-leaning think tanks such as the Heritage Foundation are routinely attacked from the left as being “radical” in nature and “out of touch” with ordinary Americans. This is nothing new. The left and progressives, especially, see this as the latest bogeyman to motivate the base as the Biden candidacy spins out of control.
What is new here is the odd tactical decision of the Biden-Harris campaign to demonize the Heritage Foundation and tie the organization’s work to Donald Trump, who has nothing to do with Heritage and had no participation with Project 2025. It’s quite doubtful Trump even knew about Project 2025 until the Biden-Harris campaign decided it would characterize it as “Donald Trump’s Project 2025 Agenda” as “something every American should be scared of.”
When we first saw references to Project 2025 appear, we knew that it was not organic. When all the usual suspects—MSDNC, CNN, the New York Times, the Washington Post, Axios, Politico, NPR, Media Matters for America, and dozens of those image memes flooding your timeline on Facebook—we knew it was no accident. As we like to say, there are no coincidences in partisan politics.
Calling this “Donald Trump’s Project 2025 agenda” is yet another droplet in the endless ocean of lies from the Biden administration and its leftwing enablers. Here is another example of the obvious disinformation coming from the left (hit the link to see how remarkably unhinged these people are).
While some of the points are true (i.e., ending the Department of Education, using public funding for private religious schools, increasing Arctic oil drilling), over 90 percent of these claims are outright lies, many of which are not even mentioned in the document. Project 2025 responded to this with an enumerated list of 30 “myths vs. facts.”
This attack on Project 2025 and the attempt to connect their agenda to Trump seem to have a very strange appeal to ignorant Biden-Harris voters. Previously, hardly anyone, even among Republican and Conservative political junkies, had even heard of the Heritage Foundation, a relatively low-key, center-right institution that has never been considered a radical fringe organization. A vast majority of Americans are now hearing about Heritage for the first time.
What might actually emerge is a broader awareness of the Heritage Foundation and its Conservative work among citizens who would not have otherwise found out if the Biden-Harris campaign had not made such a huge stink. The curiosity of voters will drive them to check out Project 2025, in which they will find five primary policy pillars intended to restore the Constitution as the country’s primary governing guide. We have distilled the five massively detailed policy proposals as follows:
First, and arguably most important, “The president must enforce the Constitution and laws as written, rather than proclaiming new ‘law’ unilaterally. Legislatures make the laws in a republic, not executives.” (With the SCOTUS controlled by its current Conservative majority, this is downright scary to far-left progressives.)
Second, “We must rediscover and adhere to the Founder’s wise division of war powers, whereby Congress, the most representative and deliberative branch, decides whether to go to war; and the executive…decides how to carry it out once begun.” Our multi-generational experimentation in presidentially initiated wars demonstrates that “we depart from our Constitutional design at our peril.” Over the vast majority of our history, especially in the 20th century, it was a Congressional Declaration of War that had the United States enter World War Two, not a Presidential Declaration of War.
Third, the president and the State Department must “stop skirting the Constitution’s treaty-making requirements and stop enforcing ‘agreements’ which haven’t been ratified by the Senate as the Constitution requires, as if they were proper treaties.” Republicans as well as Democrats are guilty of this. Is it any wonder that no new wars were started during the four years of the first Trump administration?
Fourth, “The Senate has been extraordinarily lax in fulfilling its constitutional obligation to confirm presidential appointees.” This results in unconfirmed, “acting” officials carrying out executive-branch responsibilities for months or years without Senate approval. Not to hold Democrats totally to blame here, the Senate ceded its war-making powers to the Executive Branch, starting with George W. Bush and continuing through the Obama and Biden administrations. Our growing involvement in the Ukraine conflict serves no real United States policy agenda other than to keep deep state warmongers like Victoria Nuland happy under Republican as well as Democrat administrations.
Fifth, the Justice Department must “respect the constitutional guarantee of freedom of speech rather than try to police speech.” Oh my God, where do we start here? The encroachment on the First Amendment started under Bush with the Patriot Act in the aftermath of 9/11 and has accelerated since then, especially under Obama and Biden. Biden’s Department of Justice especially has used deep state violations of its police powers against ordinary citizens, like many of the J6 demonstrators as well as journalists who neglect to toe the administration’s line.
Each of these five points is a cap, not an expansion, of presidential power. The Biden-Harris campaign making such an effort to characterize Project 2025 as enabling a presidential power grab is a classic case of projection.
Tying Trump to Heritage is a losing proposition, indicative of a campaign in desperation to change the subject from their complete and total meltdown in the wake of Biden’s catastrophic performance in the first debate and his subsequent interview with former Bill Clinton operative, George Stephanopoulos. It will backfire as expected and could lead to a broadening of acceptance toward Conservative principles among the American population.
Keep up the good work, Democrats!
***
Richard Truesdell is a former consumer electronics retail executive and automotive travel photojournalist. In the last 25 years, he has visited more than 35 countries on six continents. A former high school history teacher with a BA in Political Science from Waynesburg University, he is a lifelong Conservative moderate who has turned his thoughts and keyboard to political commentary and popular culture. A cross-section of his writings can be found here.
Keith Lehmann is a retired consumer electronics industry executive who has written extensively on technology, transportation, and international travel. Living in Southern California for over fifty years, he has first-hand exposure to societal and cultural happenings of the left and submits decidedly realism-based, Conservative viewpoints, much of which can be found on his Substack.
https://www.zerohedge.com/political/project-2025-and-continued-democrat-meltdown
5 Neuro Data Readouts to Watch in the Second Half of 2024
The first half of 2024 was filled with ups and downs for patients and researchers in the neurological disease space. The amyotrophic lateral sclerosis community took a hit when Amylyx’s Relyvrio failed its confirmatory Phase III trial and was subsequently withdrawn from the market. Huntington’s disease patients saw new hope in the form of positive mid-stage data from Wave Life Sciences.
The second half of the year kicked off with the approval of a novel disease-modifying treatment for Alzheimer’s disease, only the second such option now available to patients. The next six months are shaping up to be just as eventful in clinical research, with key data readouts expected in Alzheimer’s, schizophrenia, depression and a couple of rare diseases.
Graig Suvannevejh, senior biopharmaceuticals and biotechnology equity research analyst at Mizuho Americas, noted several key upcoming data readouts in both the neuropsychiatric and neurodegenerative spaces. Here are five BioSpace is keeping a close eye on.
Athira Pharma’s Fosgonimeton
Alzheimer’s disease
Recently approved medicines Leqembi and Kisunla command the most attention in the Alzheimer’s disease treatment space as the first anti-amyloid antibodies on the market, but the experimental Alzheimer’s pipeline is still robust. One candidate with a different mechanism of action is fosgonimeton, currently in a Phase II/III trial. Topline data from the trial, which includes around 550 patients, are expected in the second half of this year.
Developed by Athira Pharma, fosgonimeton is designed to modulate the HGF/MET system to activate neuroprotective and anti-inflammatory pathways in the central nervous system.
Athira presented data from the Phase II SHAPE trial in Parkinson’s disease dementia and dementia with Lewy bodies at the AD/PD 2024 International Conference in March, showing “encouraging safety and pro-cognitive measures.” These results “underscore confidence” in the Phase II/III LIFT-AD trial in Alzheimer’s disease, according to the company’s press release.
In 2022, fosgonimeton combined with standard-of-care acetylcholinesterase inhibitors missed the primary endpoint in Athira’s Phase II ACT-AD study, failing to best placebo in ERP P300 latency, a measure of working memory processing speed. However, a planned analysis of subgroup data showed cognitive and functional improvements through the drug’s modulation of the HGF/MET system, and Athira moved forward investigating fosgonimeton as a monotherapy for Alzheimer’s.
AbbVie/Cerevel’s Emraclidine
Schizophrenia
In December 2023, AbbVie invested nearly $9 billion in the schizophrenia space with the acquisition of Cerevel Therapeutics and its late-stage asset emraclidine. (This deal has not yet closed.) Later this year, the company will learn whether its investment has paid off.
Two Phase II trials, EMPOWER-1 and EMPOWER-2, comprise approximately 750 individuals in total and are projected to read out by the end of 2024. In these trials, AbbVie is seeking the rapid improvement of schizophrenia symptoms. The trials’ primary endpoint is change from baseline after six weeks on the Positive and Negative Syndrome Scale (PANSS) scale. The studies are also evaluating the safety and tolerability of emraclidine, a positive allosteric modulator of the muscarinic M4 receptor.
AbbVie will need strong data from the EMPOWER trials to keep pace with Bristol Myers Squibb, which is expecting an FDA decision in September on its own novel schizophrenia treatment, KarXT, which also targets the M4 as well as M1 muscarinic receptors. BMS obtained KarXT in its December acquisition of Karuna Therapeutics.
“[Emraclidine] is behind,” Suvannevejh said. “Cerevel knew that they needed to play catch-up versus Karuna,” so they tried to design the Phase II studies to be large enough and robust enough to be considered by the FDA as Phase III studies. “We don't know if FDA is going to agree to that, [but] that’s what their hope is going to be.”
Neumora Therapeutics’ Navacaprant
Major depressive disorder
Also in the neuropsychiatric space, Watertown, Mass.–based Neumora Therapeutics is expecting the first Phase III data for its lead asset navacaprant, a Kappa-opioid receptor (KOR) antagonist in development for major depressive disorder (MDD), in the fourth quarter of this year.
The KOR system is a “well-characterized pathway known to mediate depressive-like states, and modulating this system represents a novel approach to treating MDD and other major neuropsychiatric disorders,” according to Neumora’s website.
Mizuho is “bullish” on navacaprant’s prospects, due to “de-risking” Phase II data, validation from a competitor program, a positive reception from key opinion leaders on the KOR class and a large, addressable MDD market, Suvannevejh wrote in a July 8 investor note.
“This represents a brand-new class for depression,” Suvannevejh said, adding that there is a “fair amount of industry excitement” around KOR antagonists due to the less-than-ideal side effects associated with currently marketed antidepressants.
Neumora launched the Phase III trial in July 2023 after navacaprant monotherapy demonstrated “statistically significant and clinically meaningful reductions in symptoms of depression and anhedonia” in Phase II trial participants with moderate-to-severe MDD. If these studies are successful, Neumora intends to file a New Drug Application with the FDA for navacaprant in 2025.
Amylyx’s AMX003
Wolfram syndrome
A week after announcing the voluntary withdrawal of recently approved ALS treatment Relyvrio (AMX0035) from the U.S. and Canadian markets, Amylyx received a glimmer of hope for the drug—a combination of sodium phenylbutyrate and taurursodiol—in another neurodegenerative condition: Wolfram syndrome.
Wolfram syndrome is characterized by childhood-onset insulin-dependent diabetes mellitus and progressive optic atrophy, with many patients also developing diabetes insipidus, sensorineural hearing loss and autonomic nervous system degeneration. The multi-organ disease is caused by mutations in the WFS1 gene that lead to endoplasmic reticulum (ER) stress and mitochondrial dysfunction, which causes “lack of function across many different cell types, and ultimately, cell death across multiple cell types, starting with beta cells in the pancreas and then moving to parts of the nervous system,” explained Justin Klee, co-CEO of Amylyx. “AMX0035 targets ER stress and mitochondrial dysfunction.”
Interim results from the ongoing Phase II HELIOS trial showed AMX0035 improved pancreatic function and glycemic control in adult patients with the rare, inherited disease. Treatment with Amylyx’s drug led to an increase in total C-peptide response, an established marker of pancreatic beta cell function and glycemic control and the trial’s primary efficacy measure.
With these data, from eight patients who had completed 24 weeks of treatment, Amylyx co-CEO Josh Cohen told BioSpace that the company plans to engage with regulators on a possible development path for AMX0035 in Wolfram syndrome. Amylyx expects topline data from all 12 trial participants after 24 weeks of treatment during the second half of 2024.
Vigil Neuroscience’s Iluzanebart
ALSP
Another company anticipating mid-stage data for a rare disease candidate is Vigil Neuroscience. Vigil is developing iluzanebart for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), an inherited, autosomal dominant neurological disease affecting approximately 10,000 people in the U.S. Phase II data are expected in the third quarter of 2024.
ALSP is caused by loss-of-function mutations in the CSF1R gene, leading to microglial dysfunction. Iluzanebart is designed to increase signaling through DAP12/SYK to mitigate microglial dysfunction, according to Vigil. In preclinical studies, iluzanebart has “demonstrated sub-nanomolar potency and selective target engagement with TREM2,” which activates the cascade of downstream signals to mediate neuroprotective and homeostatic functions of the microglia.
“It's important for Vigil and it's important for patients with this disease because there are no FDA-approved treatments . . . and Vigil is the only game in town for this disease,” Suvannevejh said. “It’s a very novel agent targeting this TREM2 mechanism of action,” and for investors, the jury is still out on whether this is an effective approach, he said.
https://www.biospace.com/article/5-neuro-data-readouts-to-watch-in-the-second-half-of-2024-/
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