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Skin in the Game: Oruka Takes on Blockbuster Drugs for Psoriasis, Dermatological Disorders

Lawrence Klein, PhD, CEO, Oruka Therapeutics

Oruka Therapeutics wanted to go public as it prepares to advance its co-lead pipeline programs into the clinic next year. ARCA Biopharma, which first went public in 1997, sought to conclude the strategic review it launched nearly two years ago, after its candidate for hospitalized COVID-19 patients failed a mid-stage clinical trial.

Both companies have found answers in each other. Oruka and ARCA are pursuing a reverse merger intended to create a $300 million-plus combined company focused on treating plaque psoriasis and other chronic skin diseases with therapies designed to inhibit two interleukins, IL-17A/F and IL-23p19.

The combined company, which will carry on the name Oruka Therapeutics, aims to develop best-in-class, long-acting antibodies against validated targets known to play key roles in dermatologic and inflammatory diseases.

If the merger goes through as planned, the new Oruka will launch with a $275 million private investment in public equity (PIPE) transaction and a public listing on Nasdaq under the ticker symbol “ORKA.” That financing—plus $37.4 million in ARCA’s existing cash and cash equivalents as of December 31, 2023—is expected to provide Oruka more than three years of capital, allowing it to fund its operations through the end of 2027.

During that period, the combined company plans on advancing to clinical trials its two lead candidates: ORKA-001, an antibody targeting IL-23p19 with potential indications in psoriasis; and ORKA-002, an antibody targeting IL-17A/F that has numerous potential dermatological applications, including psoriasis and psoriatic arthritis.

Oruka expects to launch a first in human trial of ORKA-001 during the first half of 2025 and report initial pharmacokinetic data from healthy volunteers in the second half of next year, the same timeframe the company has set for a first in human study of ORKA-002. The first data for ORKA-002 is expected in early 2026.

“We wanted to access the public markets as we bring these programs into the clinic,” Lawrence Klein, PhD, Oruka’s CEO, told GEN Edge. “We think that we’ll have potential for early inflection points like showing our extended half-life in Phase I trials, and that having access to the public markets through those events, could be beneficial to the company for extending our cash runway.”

The combined company says it will be able to fund its operations through the end of 2027 as a result of the merger, and especially through the PIPE financing—Two and a half years longer than the cash runway of ARCA, which will run through mid-2025.

$50B+ Market by 2028

In announcing its planned reverse merger with ARCA, Oruka identified an addressable market for ORKA-001 and -002 that stood at $38 billion in 2022, but the company expects will exceed $50 billion by 2028, based on internal analysis and data from EvaluatePharma, GlobalData, Barclays, and TD Cowen.

More than half of that market is psoriasis, expected to climb by 2028 from $25 billion to $32 billion. Next highest is psoriatic arthritis (from $7 billion to $10 billion), followed by ankylosing spondylitis ($4 billion to $6 billion), then hidradenitis suppurativa ($2 billion to $4 billion).

Andrew Blauvelt, MD, chair of Oruka Therapeutics’ Scientific Advisory Board

Oruka—whose name combines the Hebrew words for skin (“or”) and restoration (“arukah”)—is based on the dermatological expertise of Andrew Blauvelt, MD, who chairs the company’s scientific advisory board. Blauvelt was President and owner of the Oregon Medical Research Center from 2013–22, a clinical research venue where he also served as investigator from 2011 until March.

Blauvelt told GEN that ORKA-001 is designed to compete with several dominant drugs. Four of those are IL-23 inhibitors—including AbbVie’s Skyrizi® (risankizumab), Janssen Biotech (Johnson & Johnson)’s Tremfya® (guselkumab) and Stelara® (ustekinumab), and Sun Pharmaceutical Industries’ Ilumya® (tildrakizumab-asmn). Another three potential competitor therapies are IL-17 inhibitors that include Novartis’ Cosentyx® (secukinumab), Eli Lilly’s Taltz® (ixekizumab), and UCB’s Bimzelx® (bimekizumab-bkzx).

Skyrizi is the best seller among IL-23 inhibitors, finishing 2023 with $7.763 billion in net revenues, up 50% from 2022. Next highest is Stelara with $10.858 billion (up 12%), followed by Tremfya with $3.147 billion (up 18%). Sun does not disclose Ilumya sales, which Oruka pegged at about $1 billion for psoriasis alone.

Among IL-17 inhibitors, Cosentyx led the field with $4.98 billion (up 4% from 2022), followed by Taltz with $2.76 billion (up 11%), then Bimzelx with €148 million ($157.5 million) in its first year on the market.

Extended and higher dosing

Oruka plans to compete with established drugs in part by extending the half-life of its IL-23 inhibitor to get less frequent dosing—as little as once or twice a year, Blauvelt said, compared with dosing frequencies ranging from every two months to quarterly (after an initial four-week interval) for the IL-23 inhibitors, and once or twice monthly for IL-17 inhibitors.

Blauvelt and Oruka also reason that they can compete with established dermatological drugs through higher dosages. Blauvelt has studied that in recent years as Oregon Medical Research Center has conducted the Phase II KNOCKOUT trial (NCT05283135), assessing whether higher initial doses of Skyrizi (300 mg and 600 mg, twice and four times the standard initial doses for plaque psoriasis) can more effectively target resident memory T cells. KNOCKOUT is also examining whether the higher doses would lead to higher levels of completely clear skin for longer periods of time following withdrawal of Skyrizi.

“It’s a marriage of extended dosing and my idea of dosing higher,” Blauvelt said. “Putting those together, our aspirations are that we think we will be able to get complete clearance rates with the Oruka compound that are several degrees higher than any of the best drugs on the market. Perhaps in the 80% range of complete clearance with higher than usual dosing. And then, we think we can possibly get to once-a-year dosing.”

In the early 2000s, Blauvelt began to study psoriasis in depth as a professor of dermatology at Oregon Health & Science University (OHSU) and chief of dermatology at the VA Medical Center in Portland, OR. Blauvelt’s lab studied how IL-23 and T helper 17 (Th17) cells played key roles in the pathogenesis of psoriasis.

IL-23 was found to be the master cytokine regulator or orchestrator of the inflammation that occurs in lesions of psoriasis (“I call it the head of the snake,” Blauvelt quips), and regulates production of another cytokine, IL-17, which acts on keratinocytes, the most prominent cells within the epidermis, to make them proliferate.

Why not target both IL-23 and IL-17 in a single drug? Because IL-23 inhibition only knocks out 90% of IL-17 production, and IL-17 inhibitors work better in psoriatic arthritis. Also, IL-23 inhibition allows for the longer dosing sought by Blauvelt and Oruka.

“What has emerged now in the field as a best of care or gold standard of care is to use an IL-23 inhibitor for two-thirds of the patients that don’t have joint disease. An IL-17 inhibitor would be best in class or gold standard for someone with concomitant psoriatic arthritis,” Blauvelt said.

At OHSU, Blauvelt organized a multidisciplinary center for care of complicated psoriasis patients and began participating in pivotal psoriasis clinical trials. Before focusing on dermatology, Blauvelt was a senior investigator at the NIH, where he pioneered research into HIV and some of its initial targets, Langerhans cells, and also studied how human herpes viruses cause Kaposi’s sarcoma and pityriasis rosea.

Struggling Since 2018

Headquartered in Westminster, CO, ARCA has struggled since 2018, when investors sent the company’s shares tumbling after the company released mixed results from the Phase IIb GENETIC-AF trial (NCT01970501  assessing the genetically targeted beta blocker GencaroTM (bucindolol hydrochloride) as a treatment for atrial fibrillation in patients with heart failure and reduced left ventricular ejection fraction.

In all 267 patients studied, Gencaro showed a treatment benefit similar to the trial’s control, metoprolol succinate, though the 127 U.S. patients showed what ARCA called potential superior benefit in favor of Gencaro—which ARCA inherited through a merger wiith Nuvelo in 2008. ARCA and the FDA later agreed on a protocol for a Phase III trial of Gencaro, which the cash-strapped never launched.

Instead, when the COVID-19 pandemic emerged in 2020, ARCA pivoted to development of the tissue factor inhibitor rNAPc2 (AB201) as a treatment for COVID-19 associated coagulopathy and related inflammatory response.

That effort failed in March 2022 when ARCA reported results from the 160-patient Phase IIb ASPEN-COVID-19 trial (NCT04655586) showing that neither of two doses of rNAPc2 achieved statistical significance for the primary efficacy endpoint of change in D-dimer level from baseline to day eight compared to the standard of care, heparin.

In May of that year, ARCA hired Ladenburg Thalmann as financial advisor and began reviewing strategic options to maximize shareholder value that it said would include “the potential for an acquisition, merger, business combination, or other strategic transaction involving the company.”

Klein said Oruka was attracted to ARCA because of its willingness to help Oruka access public markets.

“There are different ways of doing that. A reverse merger is one way that can actually be very expeditious, and that’s helpful in an election year, where the second half of this year is a bit uncertain on a number of levels,” Klein said. “We like this path, we were able to find a great partner in ARCA to allow that to move forward, and we’re excited to announce the transaction.”

From CRISPR to “compelling”

Klein became Oruka’s CEO at launch in February, following a year as a partner at venture capital firm Versant Ventures, then previously chief operating officer and chief business officer at CRISPR Therapeutics. At CRISPR, he oversaw expansion of the staff from 25 to 550 people as the company built a pipeline led by Casgevy™, which made history in December when it won the FDA’s first-ever approval for a CRISPR-edited therapy in sickle cell disease (followed in January by approval in beta thalassemia).

When he came across Oruka, Klein recalled, “I started talking to the investors behind the company. It was an idea at that stage, and their candidates were in the research phase. But just as I learned more about it, I actually spent time with Andy [Blauvelt]. It was very compelling for me to hear that part of the story, and the work he’d done. I just became more and more convinced that this is just a fantastic opportunity to offer something different to patients in a very important indication.”

“Everyone knows someone that’s affected by these diseases. And the possibility that we could offer something truly different without embarking on unproven biology, the idea that we could use Andy’s foundation plus these technology innovations around half-life extension to potentially offer patients more freedom from these diseases, I just was very, very compelled and had to have in.”

Klein will join Oruka’s board along with his former boss at CRISPR Therapeutics, its CEO and chairman Samarth Kulkarni, PhD. Joining them on Oruka’s board will be Peter Harwin, Managing Member of Fairmount; Cameron Turtle, DPhil, CEO of Spyre Therapeutics; and Carl Dambkowski, MD, CMO of Apogee Therapeutics.

Oruka acquired its rights to develop ORKA-001 and -002 from Paragon Therapeutics, a joint venture founded in 2021 by Fairmount with FairJourney Biologics, from which Oruka was spun out earlier this year.

Oruka is the third company founded to develop Paragon-generated therapies. The other two are Spyre, a developer of treatments for inflammatory bowel disease, and Apogee a developer of biologics to treat atopic dermatitis, chronic obstructive pulmonary disease, and other inflammatory and immune diseases with high unmet need.

“Growing rapidly”

The Oruka-ARCA combined company will draw upon Paragon’s 34 staffers, who will support development of ORKA-001 and -002 up to Phase I; and Oruka’s six staffers—a number Klein said expected to quadruple in 2024.

“We have plans to be 25 by the end of the year. We’re growing rapidly,” Klein said.

In addition to ORKA-001 and -002, Oruka’s pipeline includes a preclinical program with an undisclosed target that will apply a tissue-resident memory mechanism of action; as well as undisclosed combination treatment programs.

Immediately before the merger closes, ARCA said, it expects to contribute $5 million to the combined company, and expects to pay a dividend to its pre-merger stockholders of approximately $20 million.

Holders of ARCA shares before the merger are expected to own approximately 2.38% of the combined company—a percentage subject to adjustment based on the amount of ARCA’s net cash at the closing date. Pre-merger Oruka stockholders (including investors participating in the pre-closing financing) are expected to own nearly all of the combined company, approximately 97.62%.

The boards of both Oruka and ARCA have approved the merger, which is expected to close in the third quarter subject to conditions that include approvals by the stockholders of each company; the effectiveness of a statement registering the securities to be issued in connection with the merger, to be filed with the U.S. Securities and Exchange Commission (SEC); and satisfaction of customary closing conditions.

Oruka says it has commitments from a syndicate of healthcare investors for a $275 million private investment in its common stock, and pre-funded warrants to purchase its common stock. The financing is expected to close immediately before completion of the merger.

The investor syndicate is led by Fairmount and Venrock Healthcare Capital Partners, with participation from RTW Investments, Access Biotechnology, Commodore Capital, Deep Track Capital, Perceptive Advisors, Blackstone Multi-Asset Investing, Avidity Partners, Great Point Partners, Paradigm BioCapital, Braidwell, and Redmile Group, as well as other unnamed investors that include “multiple” large investment management firms.

“Launching Oruka with such strong investor support is a testament to the company’s differentiated portfolio, experienced leadership team, and focused strategy to transform the treatment paradigm across multiple chronic skin diseases,” stated Evan Thompson, PhD, Paragon’s chief operating officer.

Muscle Cell Atlas to Strengthen Research into Age-Related Deterioration

Researchers at the Wellcome Sanger Institute and at Sun Yat-sen University have generated what they claim is the first comprehensive atlas of aging muscles in humans. The team applied single-cell technologies and advanced imaging to analyze human skeletal muscle samples from 17 individuals across the adult lifespan. Their resulting map provides new insights into the many complex processes underlying age-related muscle changes, and revealed new cell populations that may explain why some muscle fibers age faster than others. The study also identified compensatory mechanisms the muscles employ to combat aging and could point to strategies for therapies and interventions that improve muscle health and quality of life as we age.

This study was carried out as part of the international Human Cell Atlas initiative that aims to map every cell type in the human body.  Sarah Teichmann, PhD, at the Wellcome Sanger Institute, is co-founder of the Human Cell Atlas, and senior author of the team’s reported study. Commenting on the findings, Teichmann said, “Through the Human Cell Atlas, we are learning about the body in unprecedented detail, from the earliest stages of human development through to old age. With these new insights into healthy skeletal muscle aging, researchers all over the world can now explore ways to combat inflammation, boost muscle regeneration, preserve nerve connectivity, and more. Discoveries from research like this have huge potential for developing therapeutic strategies that promote healthier aging for future generations.”

Teichmann and colleagues described the study in a paper in Nature Aging titled “Human skeletal muscle aging atlas.”

Skeletal muscle makes up 40% of our body mass, is essential for movement and has pivotal roles in metabolism and immune regulation, the authors wrote. “The major components of skeletal muscle, the multinucleated myofibers (MFs), are classified into ‘slow-twitch’ (type I) and ‘fast-twitch’ (type IIA, type IIX and intermediate hybrid fibers) according to their contraction speed, structural protein composition and metabolic characteristics (oxidative versus glycolytic).” Slow-twitch fibers are designed more to enable endurance activities, while fast-twitch fibers enable more powerful, explosive movements. The myofibers are also surrounded by mononuclear muscle stem cells (MuSCs), which can generate new muscle after damage.

As we age, our muscles progressively weaken. This can affect our ability to perform everyday activities such as standing up and walking. For some people, muscle loss worsens, leading to falls, immobility, a loss of autonomy and a condition called sarcopenia. “Skeletal muscle aging is characterized by the loss of both muscle mass and strength, often leading to sarcopenia,” the team continued.

During aging, there is a selective decrease in both the number and size of fast-twitch MFs, they noted. “Furthermore, the number of MuSCs and their activation and proliferation in response to stimuli decrease with age.” However, the reasons why our muscles weaken over time have remained poorly understood, and most previous studies focused on one particular mechanism or cell type, “leaving a gap in our understanding of muscle aging as a whole.”

To generate their aging muscle atlas the researchers used both single-cell and single-nucleus sequencing techniques along with advanced imaging to analyse human muscle samples from 17 individuals aged 20 to 75 years. “… In the present study, we combined scRNA-seq and snRNA-seq to build a human skeletal muscle aging atlas that includes both MuSCs and MF nuclei as well as cells from the microenvironment,” they explained. Because a muscle fiber consists of just one cell, but many nuclei, it brings unique challenges for study. Both single-cell RNA sequencing and single-nucleus RNA sequencing methods were used to address these challenges. While single-cell RNA sequencing looks at individual cells, including less common types of muscle stem cells and other supporting cells, profiling muscle fibers is difficult. Single-nucleus RNA sequencing, on the other hand, can focus on the multiple cell nuclei scattered throughout the muscle cell, to better explore its genetics.

In total, the team carried out transcription profiling of 90,902 cells and 92,259 nuclei from from the samples. “This allowed us to investigate transcriptional changes of MuSCs, MFs and microenvironment cells during aging,” they stated.

The results showed that genes controlling ribosomes, responsible for producing proteins, were less active in muscle stem cells from aged samples. This impairs the cells’ ability to repair and regenerate muscle fibers as we age. Further, non-muscle cell populations within these skeletal muscle samples produced more of a pro-inflammatory molecule called CCL2, attracting immune cells to the muscle and exacerbating age-related muscle deterioration. “In the MuSC compartment, we found downregulation of ribosome assembly resulting in decreased MuSC activation as well as upregulation of pro-inflammatory pathways, such as NF-κB, and increased expression of cytokines, such as CCL2,” they stated. In the MF microenvironment, we found several cell types that expressed pro-inflammatory chemokines, such as CCL2, CCL3 and CCL4. These cytokines may mediate the recruitment of lymphoid cells into muscle and the pro-inflammatory environment of aged muscle.”

Age-related loss of a specific fast-twitch muscle fiber subtype, key for explosive muscle performance, was also observed. However, they discovered for the first time several compensatory mechanisms from the muscles appearing to make up for the loss. These included a shift in slow-twitch muscle fibers to express genes characteristic of the lost fast-twitch subtype, and increased regeneration of remaining fast-twitch fibre subtypes.

The team also identified specialized nuclei populations within the muscle fibers that help rebuild the connections between nerves and muscles that decline with age. Knockout experiments in lab-grown human muscle cells by the team confirmed the importance of these nuclei in maintaining muscle function. “Our atlas also highlights an expansion of nuclei associated with the neuromuscular junction, which may reflect re-innervation, and outlines how the loss of fast-twitch myofibers is mitigated through regeneration and upregulation of fast-type markers in slow-twitch myofibers with age,” the team stated.

Study co-senior author Hongbo Zhang, PhD, from Sun Yat-sen University, said, “In China, the U.K. and other countries, we have aging populations, but our understanding of the aging process itself is limited. We now have a detailed view into how muscles strive to maintain function for as long as possible, despite the effects of aging.” Study first author Veronika Kedlian, PhD, at the Wellcome Sanger Institute, added, “Our unbiased, multifaceted approach to studying muscle aging, combining different types of sequencing, imaging and investigation reveals previously unknown cellular mechanisms of aging and highlights areas for further study.”

Asahi Kasei and Axolabs Partner on Oligonucleotide Therapeutics

Asahi Kasei Bioprocess (AKB), which specializes in oligosynthesis equipment, and Axolabs formed a strategic partnership in the field of oligonucleotide therapeutics. The companies will collaborate to build an oligonucleotide cGMP manufacturing facility spanning an area of 59,000 ft2 (approximately 5,481m2) in Berlin. The partners aim to accelerate the development and commercialization of oligo-based therapies.

Axolabs, a CRDMO providing drug substances for oligo-based therapeutics, is establishing a new GMP manufacturing hub in Berlin. The facility is designed to accommodate a range of production scales (small to large/commercial) and will benefit from AKB’s suite of oligo manufacturing equipment—covering all upstream and downstream manufacturing unit operations from synthesis to concentration—all of which is purpose-built to maximize productivity and provide years of reliable operation, according to Chris Rombach, SVP of sales and marketing at AKB.

“We are thrilled to join forces with Axolabs in this transformative endeavor. Our combined technical expertise and strategic alignment will bolster our commitment to meet and exceed the growing needs of the oligonucleotide therapeutics field,” said Rombach. “Moreover, our involvement from the early stages of the project allows us to support and facilitate our respective strengths.”

“We are confident that this collaboration will foster innovation and drive the production of high-quality oligonucleotide therapeutics,” added Thomas Rupp managing director of technology and production at Axolabs.

Operations at the newly built facility are planned to commence in late 2024.

Rheumatoid Arthritis: Pain without Inflammation Due to Nerve-Rewiring Genes

Treatment for rheumatoid arthritis (RA) has come a long way in recent years, and a battery of antirheumatic medications can in many cases successfully stymy the inflammatory cells that cause swelling and pain when they infiltrate tissues around the joints. Yet for some reason, about 20% of patients with painful, visibly swollen joints consistently get no relief from multiple rounds of even the strongest of these anti-inflammatory drugs.

Surgical interventions intended to remove inflamed tissue have revealed why: “In some cases, their joints aren’t actually inflamed,” noted co-senior author Dana Orange, MD, an associate professor of clinical investigation in Rockefeller’s Laboratory of Molecular Neuro-oncology. “With these patients, if you press on the joint, it feels mushy and thick to the touch, but it’s not caused by the infiltrating immune cells. They have excessive tissue growth, but without inflammation. So why are they experiencing pain?”

Newly reported research by Orange and colleagues now suggests an explanation. Using a machine-learning approach they developed called graph-based gene expression module identification (GbGMI), the team identified a suite of 815 genes that activate abnormal growth of sensory neurons in tissues that cushion the affected joints. “These 815 genes are rewiring the sensory nerves, which explains why anti-inflammatory drugs don’t work to alleviate pain for these patients,” said Orange. The findings, they suggest, may lead to new treatments for these outliers.

Reporting on their results in Science Translational MedicineSynovial fibroblast gene expression is associated with sensory nerve growth and pain in rheumatoid arthritis,” co-senior author Orange, et al., concluded, “Together, this work identifies a group of genes associated with patient report of pain in low inflammatory synovium in both early untreated and established RA … These findings have the potential to be leveraged to develop next-generation therapeutic approaches to alleviating pain in RA, particularly in the low inflammatory pathotype that may be less responsive to current therapeutics that target adaptive immune inflammation.”

Rheumatoid arthritis is a tricky chronic disease characterized by inflammation in the synovium, the tissue that lines the joint cavity. Its symptoms—stiffness, tenderness, swelling, limited motion, and pain—slowly emerge in the hands, wrists, feet, and other joints. It occurs symmetrically (not just in one hand but in both, for instance) and sporadically, with irregular flare-ups. Extreme fatigue and depression are also common.

Most cases of RA are caused by products of immune cells such as cytokines, bradykinins, or prostanoids invading the synovium—a soft tissue lining the joints—where they bind to damage-sensing pain receptors. Drugs that target immune mediators have made RA a far more tolerable condition for most, the team wrote. “Remarkable progress has been made in developing an array of conventional synthetic, targeted synthetic, and biologic disease-modifying antirheumatic drugs (csDMARDs, tsDMARDs, and bDMARDs, respectively), which target relevant immune mediators.”  However, RA patients suffering from the disconnection between inflammation and aches haven’t benefitted. “… up to 20% of patients with RA are ‘difficult to treat;’ that is, they do not improve despite treatment with at least two bDMARDs or tsDMARDs, with different mechanisms of action, after failing a csDMARD,” the investigators pointed out.

It has been assumed that synovial inflammation is the cause of RA joint pain. However, recent studies have shown that pain can be dissociated from inflammation in RA. “Patients with RA and limited synovial inflammation, also known as ‘fibroid,’ ‘low inflammatory,’ ‘pauci-immune,’ or ‘fibroblast cell type abundance phenotype’ synovium, have as much pain as those with extreme inflammation,” the scientists noted. Doctors often prescribe these patients drug after anti-inflammatory drug in an ultimately fruitless attempt to give relief. However, the scientist stated, “Patients with low synovial inflammation tend to receive less benefit from treatment with anti-inflammatory drugs…”.

Orange added, “We are subjecting some patients to a lot of medications that cause immunosuppression and yet have little chance of making their symptoms better.” For their newly reported research, Orange and colleagues sought answers in the genes expressed in the joint tissue samples of these patients. The authors commented, “… we hypothesized that a focused analysis of low inflammatory synovium might identify factors beyond inflammation that relate to joint pain.”

The team looked at tissue samples and self-reported pain reports from 39 patients with RA who had pain but little inflammation. They also developed the graph-based gene expression module identification (GbGMI) machine-learning tool, which tests every possible combination of genes in a dataset to determine the optimal set of genes that together associate with a targeted clinical feature—in this case, pain.

Using RNA sequencing, the researchers found that of the 15,000 genes expressed in the tissue samples, about 2,200 had increased expression in the 39 patients. “To uncover genes associated with pain but not inflammation, we focused our analysis on 2,227 genes that exhibited increased expression in low inflammatory synovium relative to high inflammatory synovium and on pain scores that document the extent of pain in the joint that was sampled [Hip Osteoarthritis Outcome Score/Knee Osteoarthritis Outcome Score (HOOS/KOOS)],” they stated.

In this image, abnormal synovial tissue is shot through with excessive tissue growth, including blood vessels (in magenta). Synovium should be thin and smooth.
In this image, abnormal synovial tissue is shot through with excessive tissue growth, including blood vessels (in magenta). Synovium should be thin and smooth. [Bai et al]

Using GbGMI, the team identified 815 genes that together were associated with patient reports of pain. “We then tested which number of top-ranked genes collectively best correlated with pain among patients with RA with low synovial inflammation and identified an 815-gene module, which we refer to as the GbGMI-identified pain-associated genes.”

Co-senior author Fei Wang, PhD, professor of population health sciences and founding director of the Institute of Artificial Intelligence for Digital Health at Weill Cornell Medicine, added, “This is a challenging problem because we have a large number of genes but a limited number of patients. The graph-based approach we used effectively explored the collective associations between a gene set and patient-reported pain.” The team validated the findings in a second, independent dataset of synovial biopsy samples from patients with early untreated RA.“

Single-cell sequencing analysis found that of the four types of fibroblasts in synovial tissue, CD55+ fibroblasts exhibited the highest expression of pain-associated genes. “Gene expression analysis among fibroblast subsets indicated that compared with the other fibroblast subsets, lining CD55+ fibroblasts (SC-F4) exhibited the highest expression of GbGMI-identified pain-associated genes,” the authors wrote. Located in the outer synovial lining, CD55+ cells secrete synovial fluid, allowing for frictionless joint movement.

They also expressed the NTN4 gene, which codes for a protein called Netrin-4. Proteins in the netrin family guide axon growth paths and promote new vascular growth. These genes, it turned out, were enriched in pathways that are important for neuron axon growth, the researchers discovered. The keys to sensation, sensory neurons receive and transmit information to the central nervous system. Axons are the tendrils that branch out from them into tissues.

“That led us to hypothesize that perhaps the fibroblasts are producing things that alter the growth of sensory nerves,” Orange stated. But what role was the protein playing in the sensation of pain? To find out, the researchers grew neurons in vitro and then doused them with Netrin-4. This sparked the sprouting and branching of CGRP+ (gene-related peptide) pain receptors. The results represent the first time that Netrin-4 has been shown to alter the growth of pain-sensitive neurons, Orange noted.

Imaging of RA synovial tissue also revealed an overabundance of blood vessels, which feed and nurture new cells. These vessels were encased by CGRP+ sensory nerve fibers and were growing towards the lining fibroblasts in areas of excessive tissue growth, or hyperplasia. This process likely leads to the squishy swelling that many rheumatologists and surgeons have mistaken for inflammation. Reporting on the cell-based studies, the team stated, “We conclude that neoangiogenesis into abnormal papillary processes toward lining fibroblasts in the low inflammatory RA synovium was accompanied by neoneurogenesis of CGRP+ nociceptive axons.”

In the future, the researchers aim to hone in on other products that fibroblasts may be producing that can affect the growth of pain-sensitive neurons. “… these findings support a model whereby synovial lining fibroblasts express genes associated with pain that enhance the growth of pain-sensing neurons into regions of synovial hypertrophy in RA,” they wrote. “Future studies are needed to further unravel how genes identified here relate to neuron growth and patient experience of pain either independently or in conjunction with other genes.” Additional work will also be needed to explore the effects of fibroblast products on human neurons, they added. “There are also many other genes associated with patient report of pain in this dataset that warrant additional study.”

The investigators, in addition, aim to look at the other types of sensory nerves that might be affected. “We studied one type, but there are about a dozen,” Orange pointed out. “We don’t know if all nerves are affected equally. And we don’t want to block all sensation. Sensory nerves are important for knowing that you should avoid certain movements and the position of your joint in space, for instance … We want to drill down on those details so that hopefully we can come up with other treatments for patients who don’t have a lot of inflammation. Right now, they’re taking medications that can cost $70,000 a year but have no chance of working. We must do a better job of getting the right drug to the right patient.”

StockWatch: Regeneron Shares Dip as DOJ Alleges Fraudulent Price Reporting

Regeneron Pharmaceuticals (REGN) found itself in the glare of unwelcome publicity when the U.S. Department of Justice (DOJ) announced it had filed a complaint accusing the biotech giant of fraudulently reporting the price of Eylea® (aflibercept), the blockbuster eye drug it co-markets with Bayer.

The DOJ alleges that Regeneron violated the False Claims Act by fraudulently inflating the Medicare reimbursement rates it received for Eylea. According to the DOJ, Regeneron knowingly submitted false reports to the Centers for Medicare and Medicaid Services that were based on average sales price (ASP), without accounting for price concessions—namely credit card processing fees that Regeneron paid to specialty drug distributors to benefit its customers.

Regeneron paid the credit card fees so that distributors would accept credit cards for Eylea purchases while still charging a lower, cash price for the drug, the DOJ alleges. As a result, Regeneron’s customers—typically retina and ophthalmic practices—could receive credit card benefits for their purchases, such as “cash back” and other credit card rewards.

“By purporting not to offer price concessions on Eylea, Regeneron could market Eylea’s stable ASP (and stable reimbursement) as a competitive advantage for retina practices when compared to Lucentis® (ranibizumab),” the DOJ stated in its court complaint, referring to the rival eye drug marketed by Roche (ROG:SIX) and its Genentech subsidiary.

What competitive advantage?

“Regeneron knew that offering and reporting discounts would likely trigger a Genentech ‘response’ that would lead to a downward pricing spiral and risk a price war,” the DOJ argued. “Regeneron knew that Eylea’s stable ASP gave it an advantage with customers, particularly customers with smaller volumes who were not eligible for large volume-based rebates that Genentech offered for Lucentis.”

According to the DOJ’s complaint, Medicare Part B paid more than $25 billion for Eylea between 2012 and 2023.

Regeneron countered in a statement that the DOJ allegations “are without merit.”

“The complaint, which follows a Civil Investigative Demand from the U.S. Department of Justice in June 2021, and which the company previously disclosed, relates to the company’s lawful reimbursement of costs incurred by our specialty distributors,” Regeneron added. “The Government’s complaint demonstrates a fundamental misunderstanding of drug price reporting standards. Regeneron has fully cooperated with the Government’s investigation and will vigorously defend itself in court.”

Somewhat concerned

Judging by Regeneron’s stock performance since the DOJ complaint surfaced, investors seem somewhat concerned, but not terribly so. Regeneron shares have slid 4% since Wednesday, from $936.20 at that day’s close to $904.70 on Friday.

Regeneron has a market capitalization (the product of the share price and the number of outstanding shares) of $99.302 billion, above its $91.51 market cap when it ranked fifth on GEN’s A-List of Top 25 Biotech Companies of 2024.

Jefferies equity analyst Akash Tewari offered a likely reason for the apparent mild response among investors: The financial damage to Regeneron from the DOJ is unlikely to be severe.

We’re skeptical on the DOJ’s case, given these discounts could be considered as ‘bona fide services reimbursements,’ which are not included in calculating ASP,” Tewari wrote in a research note Thursday. [emphasis in original]

He based that argument on dialogue with Regeneron executives, who offered a potential preview of their response to the DOJ’s complaint by arguing that nothing in the definition of an ASP alludes to credit card fees being included in the ASP calculation: “Rather than providing an incentive or rebate, REGN believes that by reimbursing the distributor for the credit card fee, they are reimbursing for the services rendered by the distributor, and not as a discount for doctors to promote Eylea for these reasons.”

“Given that REGN is 1) reimbursing the credit card fees otherwise incurred, 2) paying under the circumstance of distributor services, and 3) not passing through the reimbursements to the retinal practices or controlling the credit card benefits doctors could receive, these reimbursements could be classified as bona fide services fees,” the company added.

“Minimal impact”

Even if Regeneron opts to settle the allegations, Tewari continued, “Our analysis suggests minimal impact to REGN.”

Regeneron also told Tewari that some of its peer companies among biopharmas similarly did not include credit card reimbursements in their ASPs, yet were not seen to be falsely inflating their prices for Medicare: “Thus given these considerations and historical precedence for similar cases, we think the overall case falls fairly weak, and if needed, payments of <$100M could be granted to settle the allegations.”

Tewari projects that based on the precedent of earlier DOJ complaints against biopharmas, “all-in-all, REGN’s actual settlement fines could be <$50M.”

$50 million to $100 million would be 1.25% to 2.5% of Regeneron’s 2023 net income. The company finished last year earning $3.954 billion (down 9% from 2022) on revenue of $13.117 billion (up nearly 8%).

“In the most bearish scenario,” Tewari cautioned, “REGN’s treble damages would add up to less than $1B”—about 25% of 2023 net income.

“We cannot predict”

Taking a more uncertain view of Regeneron’s situation is David Risinger of Leerink Partners. “This is a negative development, and we cannot predict the potential financial risk to the company.”

Risinger cited the DOJ’s policy of pursuing treble damages, plus applicable penalties, against companies found liable for violating the Fraudulent Claims Act.

“Considering those figures, we are hoping that the risk to the company is a small percentage of its 12/31/23 cash & marketable securities position,” Risinger added. Regeneron finished 2023 with cash and marketable securities of $16.241 billion, up 13% from $14.334 billion.

At deadline, only a few other analysts besides Risinger and Tewari had weighed in on Regeneron. Geoff Meachem of B of A Securities barely raised his firm’s 12-month price target on Regeneron shares 1%, from $710 to $720, though he retained B of A’s “Underperform” rating on the company’s stock.

Brian Abrahams of RBC Capital maintained its “Outperform” rating on Regeneron and kept his firm’s price target at $1,189.

Nearly half (45%) of Regeneron’s 2023 revenues reflects the $5.886 billion in U.S. net product sales racked up by its two dosages of Eylea.

The 2 mg dose of Eylea generated most of those sales at $5.72 billion, down 9% from $6.265 billion in 2022, due to growing competition. The remaining $166 million came from patients using Eylea HD, an 8 mg dosage approved by the FDA last August—and which Regeneron is counting on to gain back at least some of the lost sales.

Both versions of Eylea are indicated for neovascular (wet) age-related macular degeneration (nAMD), diabetic macular edema (DME), and diabetic retinopathy (DR). The 2 mg Eylea, which won its first FDA approval in 2011, is also indicated for macular edema following retinal vein occlusion (RVO), and retinopathy of prematurity (ROP).

Outside the United States, Bayer’s sales of Eylea were all but flat last year, inching up 0.6% to €3.231 billion ($3.437 billion) from €3.213 billion ($3.418 billion). All of those sales were for 2 mg Eylea, since Eylea HD had not received marketing authorization from the European Commission until January.

Lucentis, by contrast, saw its sales plunge 52% in 2023, from CHF 1.012 billion ($1.108 billion) to CHF 460 million ($503.5 million). Lucentis is a vascular endothelial growth factor (VEGF) inhibitor indicated for nAMD, RVO, DME, DR, and myopic choroidal neovascularization (mCNV).

Roche has blamed growing competition plus its effort to switch Lucentis patients to its next-generation eye drug Vabysmo (faricimab-svoa). That effort paid off for Roche, as Vabysmo sales last year more than quadrupled, zooming 324% from CHF 591 million ($647 million) to CHF 2.357 billion ($2.58 billion). Vabysmo is a combination VEGF and angiopoietin-2 (Ang-2) inhibitor indicated for nAMD, DME, and RVO.

In contrast to the mild response to the DOJ complaint, investors have sent Regeneron shares skidding 10% since February 28, when they reached their 2024 high of $998.33.

A key driver of that decline was the FDA: On March 25, Regeneron acknowledged that the agency issued Complete Response Letters rejecting its BLA seeking accelerated approval for its CD20xCD3 bispecific antibody odronextamab to treat relapsed/refractory (R/R) follicular lymphoma (FL) and R/R diffuse large B-cell lymphoma (DLBCL), each after two or more lines of systemic therapy.

“The only approvability issue is related to the enrollment status of the confirmatory trials,” Regeneron stated at the time. “Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion be agreed prior to resubmission.”

Leaders and laggards

  • Eliem Therapeutics (ELYM) shares soared 71.5% from $2.67 to $4.58 on Thursday, after the company said it agreed to acquire privately held Tenet Medicines. Eliem plans to fund the deal through a $120 million private placement in which it will sell 31,238,282 shares at $3.84 a share to a syndicate of new and existing institutional life science investors, including RA Capital Management, Deep Track Capital, Boxer Capital, Janus Henderson Investors, Pontifax, and Samsara Biocapital. The private placement, plus cash and cash equivalents of the combined company, are expected to total approximately $210 million. Eliem said the combined company plans to focus on advancing the anti-CD19 antibody TNT119 for a variety of autoimmune diseases, including systemic lupus erythematosus, immune thrombocytopenia, and membranous nephropathy.
  • Enlivex Therapeutics (ENLV) shares plummeted 54% from $3.98 to $1.83 on Thursday, then skidded another 14% to $1.58 on Friday, after the company announced mixed results from its 120-patient Phase II trial (NCT04612413) assessing Allocetera™ in patients with sepsis. By day 28, an analysis showed 90% reductions in sequential organ failure assessment (SOFA) scores for sepsis patients whose infection source was urinary tract, 68% for community-acquired pneumonia sepsis patients, and 36% for internal abdominal infection sepsis patients. Due to randomization, Allocetra™-treated cohorts had 20% higher frequency of septic shock and 35% higher frequency of invasive ventilation before treatment, compared with the control group. Both “are associated with a significantly higher degree of difficulty of treatment and higher mortality rates. These imbalances made it challenging to deduce the relative effect in other patient subgroups,” Enlivex stated.
  • Rallybio (RLYB) shares zoomed 83% from $1.63 to $2.98 on Thursday after the company announced a collaboration of undisclosed value with Johnson & Johnson (JNJ) subsidiary Momenta Pharmaceuticals to support developing complementary therapeutic approaches aimed at reducing the risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT). Rallybio also received a $6.6 million equity investment from J&J’s strategic venture capital arm Johnson & Johnson Innovation–JJDC, and will receive funding from J&J to promote J&J’s FNAIT clinical program in connection with Rallybio’s ongoing FNAIT natural history study (NCT05345561). Rallybio is developing RLYB212, a human monoclonal anti-HPA-1a antibody designed to prevent pregnant women from alloimmunizing. Rallybio said it is on track to launch a Phase II dose confirmation study for RLYB212 in the second half of 2024. J&J is conducting a Phase III study of nipocalimab, a monoclonal antibody targeting the neonatal Fc receptor in alloimmunized pregnant women.

Is Gene Therapy Nearing a Tipping Point?

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Gene therapy has undergone a renaissance in recent years, with several drugs offering beneficial, even life-saving treatments, now approved by the FDA. One example was reported earlier this year, with the progress made by two separate research teams working on gene therapy programs targeting hearing loss. And the FDA has stated that they expect an increase in the number of authorizations of gene therapy treatments over the next few years. But getting gene therapies into patients is a challenging road.

On this episode of GEN Live, we will discuss the state of gene therapy today, the promises and pitfalls of delivery vectors, the challenge posed by the immune response, and the safety issues that need to be addressed going forward. Dr. Federico Mingozzi, who has been working in the gene therapy field for over two decades, joins Dr. Allison May Keeler-Klunk, assistant professor at UMass Chan Medical School, to share their perspectives on the field’s current progress and future challenges.

A live Q&A session will follow the presentation, offering you a chance to pose questions to our expert panelists.

Federico Mingozzi, PhD,
Federico Mingozzi, PhD
Former CSO and CTO
Formerly Spark Therapeutics
Allison May Keeler-Klunk, PhD
Allison May Keeler-Klunk, PhD
Assistant Professor
UMass Chan Medical School

 

Launch of Nvelop Therapeutics for Delivery of Genetic Cargo, AACR Recap

Episode 17 (April 12, 2024): This week, the GEN editors discuss the launch of Nvelop Therapeutics, a new start-up leveraging approaches developed by gene editing pioneers David Liu, PhD, and J. Keith Joung, MD, PhD, to advance delivery of genetic cargo. The GEN editors also recap highlights from the American Association for Cancer Research (AACR) annual meeting held in San Diego, California.

Featuring Uduak Thomas (Senior Editor, GEN), Alex Philippidis (Senior Business Editor, GEN), Julianna LeMieux, PhD (Deputy Editor-in-Chief, GEN), and Jonathan Grinstein, PhD (Senior Editor, GEN), and moderated by Fay Lin, PhD (Senior Editor, GEN Biotechnology)

Listed below are key references to the GEN stories, media, and other items discussed in this episode of Touching Base:

The State of Omics 2024 Registration
GEN Summit

Cloaking Device: Liu, Joung Launch $100M Nvelop Therapeutics to Advance Delivery of Genetic Cargo
By Alex Philippidis, GEN Edge, April 9, 2024

Bertozzi, Regev, and More Inspire During the Opening Plenary Session of AACR
By Julianna LeMieux, PhD, GEN, April 8, 2024

AACR 2024: Aviv Regev Shows How Single-Cell Atlases Foster New Axis to Genentech’s Drug Discovery
By Jonathan Grinstein, PhD, GEN, April 8, 2024

AACR 2024: Aviv Regev Shows How Single-Cell Atlases Foster New Axis to Genentech’s Drug Discovery
By Jonathan Grinstein, PhD, GEN, April 8, 2024

AACR 2024: A Video Update from San Diego
By Julianna LeMieux, PhD, and Jonathan Grinstein, PhD, GEN, April 8, 2024

A Video Update from Day Two of the AACR Meeting
By Julianna LeMieux, PhD, and Jonathan Grinstein, PhD, GEN, April 9, 2024

AACR 2024: EpiBiologics Advances Degraders of Membrane-Bound Proteins
By Jonathan Grinstein, PhD, GEN, April 8, 2024

 

More coverage from AACR:

AACR: Colon Cancer Patients Respond to Antibody/KRAS Inhibitor Combo
GEN, April 8, 2024

AACR: Breast Cancers Have DNA Repair Crutch Kicked Away by Saruparib
GEN, April 9, 2024

AACR 2024: Geneos Therapeutics’ Vaccine Outperforms Liver Cancer Immunotherapies
By Jonathan Grinstein, PhD, GEN, April 9, 2024

Celebrating National Robotics Week
By Uduak Thomas, GEN, April 12, 2024

Celebrating National Robotics Week

National Robotics Week is intended to inspire students in robotics and STEM related fields. In honor of the week, we are highlighting some of the interesting and innovative applications of robotics and artificial intelligence in biomedical research and development from our archives.  

One recent article explored the emerging role of robots and AI in cell and gene therapy manufacturing as described in a joint paper by the European Committee of the International Society for Cell & Gene Therapy and the European Society for Blood and Marrow Transplantation. At this year’s Precision Med TRI-CON meeting, Eric Topol, MD, dubbed artificial intelligence as “the biggest transformation in the history of medicine.” Robots were also on full display at this year’s Society of Lab Automation and Screening conference including ones for liquid handling in the context of next-generation sequencing library preparation and nucleic acid extraction. There’s also increasing interest in deploying nano-sized robots to treat various cancers including bladder tumors and lung tumors 

We are also looking to the future and thinking about some of the areas that robots might move into next. Below, Opentrons CEO Jon Brennan-Badal shares his thoughts on where robots are currently at work in the life sciences and what the future might look like.  

GEN: What are some of the most exciting applications of robotics currently? 

Brennan-Badal: The robotics industry is rapidly advancing, revolutionizing sectors like healthcare and life sciences. In life sciences, robotics is crucial in high-throughput settings like core genomics facilities and labs working on discovering and screening new drugs. Automation in these settings ensures data reliability and allows for higher throughput of samples, supporting scalability. These advancements in robotics significantly enhance scientific advancement and medical breakthroughs. 

Automating routine tasks dramatically increases the number of experiments conducted and discoveries made. For instance, in sequencing, the cost of sample preparation now exceeds the use of the sequencers themselves due to manual labor. Automating these processes can significantly reduce costs and increase throughput, shifting the bottleneck away from manual labor and towards more efficient, automated solutions. This efficiency mirrors that seen in industries like manufacturing and logistics, highlighting the potential for robotics to enhance productivity in life sciences. 

GEN: What does the future of robotics in the field look like? 

Brennan-Badal: As in many industries, AI is likely to have a profound effect on lab automation and robotics. At Opentrons, we are already seeing the potential of generative AI to significantly improve automated workflows and protocol creation. By using an interface powered by generative AI and large language models, scientists can describe experimental protocols in plain language, and the model will interpret and generate corresponding automated protocol scripts intelligently. This approach suggests optimal parameters, troubleshoots potential issues, and adapts protocols based on specific experimental requirements. 

Another important consideration is preparing the next generation of scientists with crucial skills. We believe automation should be a core skill in laboratory sciences, bridging the widening skill gap in biotech. Embedding automation into educational curriculums and enabling early and effective learning of laboratory automation is setting students up for success in a dynamic biotech future. 

CRISPR Tool Shown Highly Effective at Neutralizing RNA Viruses in Cytoplasm

Researchers from Helmholtz Munich and the Technical University of Munich (TUM) report that they have developed a new tool (Cas13d-NCS) that allows CRISPR RNA molecules that are located within the cell to move to the cytoplasm to make it effective at neutralizing RNA viruses. The team says this technique, which was necessary because RNA-targeting tools like CRISPR/Cas13 are powerful but inefficient in the cytoplasm of cells where many RNA viruses replicate, opens doors for precision medicine and proactive viral defense strategies.

The scientists’ study “Engineered, nucleocytoplasmic shuttling Cas13d enables highly efficient cytosolic RNA targeting” appears in Cell Discovery.

Treatment with Cas13d-NCS prevents the spread of SARS-CoV-2 (green). [Wolfgang Wurst, PhD]
Treatment with Cas13d-NCS prevents the spread of SARS-CoV-2 (green). [Wolfgang Wurst, PhD]
“CRISPR/Cas13 systems are programmable tools for manipulating RNAs and are used in a variety of RNA-targeting applications. Within the Cas13 family, Cas13d is the most active subtype in mammalian cells. Recently, Cas13d was harnessed as an antiviral against diverse human RNA viruses,” write the investigators.

“However, Cas13d is barely active in the cytosol of mammalian cells, restricting its activity to the nucleus, which limits applications such as programmable antivirals. Most RNA viruses replicate exclusively in the cytosol, suggesting that current Cas13d-based antivirals rely on uncontrolled nuclear leakage and are therefore limited in their efficiency.

“Here, we show that the nuclear localization of Cas13d crRNAs is the fundamental cause of Cas13d’s nuclear preference. To address this limitation, we engineered nucleocytoplasmic shuttling Cas13d (Cas13d-NCS). Cas13d-NCS transfers nuclear crRNAs to the cytosol, where the protein/crRNA complex binds and degrades complementary target RNAs.

“We screened various designs of shuttling proteins and characterized multiple design parameters of the best-performing system. We show that Cas13d-NCS is superior for degrading mRNAs and a self-replicating RNA derived from the Venezuelan equine encephalitis (VEE) RNA virus.

“Ultimately, we harnessed Cas13d-NCS to completely block the replication of various SARS-CoV-2 strains. Cas13d-NCS, therefore, enables the rational manipulation of the subcellular localization of a CRISPR system.”

Screening and optimization

Through screening and optimization, the researchers developed what they label “a transformative solution: Cas13d-NCS,” a system capable of transferring nuclear CRISPR RNA (crRNAs) into the cytosol to guide the CRISPR-Cas complex to specific target sequences for precise modifications. In the cytosol, the protein/crRNA complex targets complementary RNAs and degrades them with unprecedented precision, according to the researchers.

Cas13d-NCS outperforms its predecessors in degrading mRNA targets and neutralizing self-replicating RNA, including replicating sequences of Venezuelan equine encephalitis (VEE) RNA virus and several variants of SARS-CoV-2, unlocking the full potential of Cas13d as a programmable antiviral-tool, add the scientists, who cite this achievement as representing a significant step towards combating pandemics and strengthening defenses against future outbreaks.

The impact of the study goes beyond traditional antiviral strategies and CRISPR systems and ushers in a new era of precision medicine by enabling the strategic manipulation of subcellular localization of CRISPR-based interventions, maintains Wolfgang Wurst, PhD, director of the Institute of Developmental Genetics at Helmholtz Munich.

“This breakthrough in antiviral development with Cas13d-NCS marks a pivotal moment in our ongoing battle against RNA viruses,” says Wurst, who is coordinator of the study and also chair of developmental genetics at TUM, partner of the German Center for Neurodegenerative Diseases (DZNE) and member of the Munich Cluster for Systems Neurology (SyNergy). “This achievement showcases the power of collaborative innovation and human ingenuity in our quest for a healthier and more resilient world.”

Detecting Growing Tumors through Changes in the Plasma Proteome

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For most malignancies, early tumor detection is crucial, as it expands treatment options, reduces metastases, and ultimately improves survival rates. Despite clear clinical appeal, early detection remains a considerable diagnostic challenge since small masses of tumors often remain asymptomatic and are difficult to discern from normal tissue by imaging methods.


In this GEN webinar, Nebojsa Janjic, PhD, will discuss the need for a reliable blood-based screening method capable of detecting cancers earlier. During the webinar, he will highlight results from a study involving researchers from SomaLogic and the University of Colorado School of Medicine that used a test capable of measuring 5000 proteins simultaneously. He’ll explain how scientists used the test to identify protein markers shared by multiple cancer types including lung, breast, colon, and ovarian tumors. Key learnings from the webinar include:

• How the innovative SomaScan® Platform was used to identify early protein biomarkers in plasma for four distinct tumor types.

• Findings that not only pinpoint biomarkers unique to each tumor type but also uncover 15 protein biomarkers shared across all cancer types, revolutionizing our understanding of cancer detection.

• The development of models to stratify tumor types and illuminate unique biological pathways of tumor cell lines.

A live Q&A session will follow the presentation, offering you a chance to pose questions to our expert panelist.

Webinar produced with support from:

Nebojsa Janjic, PhD
Nebojsa Janjic, PhD
Chief Scientific Officer
SomaLogic

Standard Biotools logo

 

Oruka Therapeutics and ARCA Biopharma are pursuing a reverse merger intended to create a $300 million-plus combined company focused on treating plaque psoriasis and other chronic skin diseases with therapies designed to inhibit two interleukins, IL-17A/F and IL-23p19.
Elderly exercise
Researchers used single-cell technologies and advanced imaging to analyze human skeletal muscle samples across the adult lifespan and generate a comprehensive atlas of aging muscles. The map provides insights into processes underlying age-related muscle changes, revealed cell populations that may explain why some muscle fibers age faster than others, and identified compensatory mechanisms the muscles employ to combat aging. The findings could point to strategies for therapies that improve muscle health as we age.
microscope
Axolabs, a CRDMO providing drug substances for oligo-based therapeutics, is establishing a new GMP manufacturing hub in Berlin. The facility is designed to accommodate a range of production scales (small to large/commercial) and will benefit from Asahi Kasei Bioprocess’s suite of oligo manufacturing equipment, all of which is purpose-built to maximize productivity and provide years of reliable operation, according to an official at Asahi Kasei.
Rheumatoid arthritis hands
Existing anti-inflammatory anti-rheumatic drugs may not work in about 20% of rheumatoid arthritis patients. Studies have shown that in some cases the painful, swollen joints aren’t actually inflamed. Researchers using a newly developed machine learning tool have now identified in synovial fluid samples from these patients a suite of 815 genes that activate abnormal growth of sensory neurons in tissues that cushion the affected joints. The findings could lead to new treatment approaches.
The DOJ alleges that Regeneron violated the False Claims Act by fraudulently inflating the Medicare reimbursement rates it received for Eylea. Specifically, according to the DOJ, Regeneron knowingly submitted false reports to the Centers for Medicare and Medicaid Services that were based on average sales price (ASP), without accounting for price concessions—namely credit card processing fees that Regeneron paid to specialty drug distributors to benefit its customers.
Genetic testing & genome sequencing
On this episode of GEN Live, Federico Mingozzi, PhD, and Allison May Keeler-Klunk, PhD, will discuss the state of gene therapy today, the promises and pitfalls of delivery vectors, the challenge posed by the immune response, and the safety issues that need to be addressed going forward.
Cancer cells
In this week's Touching Base podcast, the GEN editors discuss the launch of Nvelop Therapeutics, a new start-up leveraging approaches developed by gene editing pioneers David Liu, PhD, and J. Keith Joung, MD, PhD, to advance delivery of genetic cargo. The GEN editors also recap highlights from the American Association for Cancer Research (AACR) annual meeting held in San Diego, California.
Robotic equipment holding syringe in lab
In honor of National Robotics Week, we're putting a spotlight on some of the current uses of robotics and AI in the life sciences including applications in cancer and cell and gene therapy manufacturing, and how these technologies will reshape the field in future.
Flaviviridae viruses, illustration.
Scientists from Helmholtz Munich and the Technical University of Munich used screening and optimization techniques to develop what they label “a transformative solution: Cas13d-NCS,” a system capable of transferring nuclear CRISPR RNA (crRNAs) into the cytosol to guide the CRISPR-Cas complex to specific target sequences for precise modifications. The protein/crRNA complex targets complementary RNAs and degrades them with unprecedented precision, according to the researchers.
Fluorescent Imaging immunofluorescence of cancer cells growing in 2D
In this GEN webinar, SomaLogic CSO Nebojsa Janjic, PhD, will discuss the need for a reliable blood-based screening method capable of detecting cancers earlier.