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Next-generation sequencing (NGS) is continuously evolving. Traditional short-read DNA sequencing has encouraged break-throughs at ever-lower costs across the field of genomics. However, tumors, brains, the immune system, and other complex systems require the greater resolution and flexibility only recently introduced with single-cell sequencing. Compared to the more established bulk RNA sequencing (RNA-Seq), single-cell sequencing magnifies cellular differences to glean intel about how an individual cell functions in its environment. By sequencing individual cells to determine the base sequences, researchers can obtain genomic, transcriptomic, or multiomic data on a cell-by-cell basis, revealing details that are otherwise overlooked.

Single-cell sequencing applies to any study that requires detailed understanding of a cell population, marking tremendous potential for multiple research areas spanning a diversity of applications. This eBook highlights single-cell innovations and approaches, demonstrating how NGS identifies a neuroblastoma target and provides insights for brain rejuvenation and the development of combination therapies. We also invite researchers to explore how the Element AVITI System synthesizes quality, flexibility, and compatibility to deliver affordable single-cell sequencing at any scale so that you can own the next breakthrough.

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The post Explore at the Single-Cell Level: Reveal Insights Hidden in Complex Cell Populations appeared first on GEN - Genetic Engineering and Biotechnology News.

Broadcast Date: November 7, 2023
Time: 8:00 am PT, 11:00 am ET, 17:00 CET

Automated analysis of medical imaging data is just one of the ways that artificial intelligence (AI) technologies are transforming the standard of care in medicine. Across industry and academia, scientists are using AI to extract useful patterns from data, improve studies of conditions such as neurological disorders, oncology, and ophthalmology, and increasingly in the context of drug development. There are ample opportunities to leverage AI in the drug development process from discovery and development to the design, conduct, and interpretation of clinical trials. One critical area is the analysis and management of complex clinical information such as medical imaging data, which contains important insights for assessing the effectiveness of treatments. 

In this GEN webinar, Dr. Shelby Wyatt will discuss how AI-based medical imaging helps imaging/data scientists, innovators, and healthcare professionals accelerate drug development initiatives and projects and move the needle towards personalized healthcare. She will discuss how Flywheel builds reliable, scalable medical imaging solutions that seamlessly integrate advanced AI technology from NVIDIA and other technology partners to enable robust imaging data management and analysis. 

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:

The post Accelerating Drug Development Using Medical Imaging AI appeared first on GEN - Genetic Engineering and Biotechnology News.

The findings were published in the Proceedings of the National Academy of Sciences in an article titled, “Viral nanoparticle vaccines against S100A9 reduce lung tumor seeding and metastasis.”

“Metastatic cancer accounts for 90% of all cancer-related deaths and continues to be one of the toughest challenges in cancer treatment,” wrote the researchers. “A growing body of data indicates that S100A9, a major regulator of inflammation, plays a central role in cancer progression and metastasis, particularly in the lungs, where S100A9 forms a premetastatic niche. Thus, we developed a vaccine against S100A9 derived from plant viruses and virus-like particles. Using multiple tumor mouse models, we demonstrate the effectiveness of the S100A9 vaccine candidates in preventing tumor seeding within the lungs and outgrowth of metastatic disease.”

A team led by Nicole Steinmetz, PhD, a professor of nanoengineering at the UC San Diego Jacobs School of Engineering, developed a vaccine candidate that can modulate the levels of S100A9 when it goes haywire. When injected subcutaneously, the vaccine stimulated the immune system in mice to produce antibodies against S100A9. The vaccine also increased the expression of immune-stimulating proteins with anti-tumor properties, while decreasing the levels of immune-suppressing proteins.

“S100A9 is known to form what is called a premetastatic niche within the lungs, creating an immunosuppressive environment that allows for tumor seeding and growth,” said study first author Young Hun (Eric) Chung, a UC San Diego bioengineering PhD alumnus from Steinmetz’s lab. “By reducing S100A9 levels, we can effectively counteract the formation of this premetastatic niche, leading to a reduced attraction and increased clearance of cancer cells to the lungs.”

“This is a clever, new approach to vaccination in that we are not targeting tumor cells, but rather the tumor microenvironment so that it prevents the primary tumor from making new tumors,” said Steinmetz, who is also the founding director of the UC San Diego Center for Nano-ImmunoEngineering and co-lead of the university’s Materials Research Science and Engineering Center (MRSEC). “We are essentially changing the whole immune system to be more anti-tumor.”

The vaccine consists of nanoparticles made from a bacterial virus called Q beta. The nanoparticles were grown from E. coli bacteria and isolated. Afterward, a piece of the S100A9 protein was attached to the surface.

“With this form of immunotherapy, we are not necessarily knocking out all of the protein, but we are reducing the levels everywhere,” said Steinmetz.

The vaccine was tested in metastatic mouse models of melanoma and triple-negative breast cancer. Healthy mice were first administered the vaccine, then challenged with either melanoma or triple-negative breast cancer cells through intravenous injection. Vaccinated mice exhibited a significant reduction in lung tumor growth compared to unvaccinated mice. In unvaccinated mice, the injected cancer cells circulated throughout the body and eventually homed in on the lungs to form metastatic tumors.

The researchers noted that this vaccine strategy combats tumor spread, not the primary tumor itself.

“While S100A9 does get overexpressed in certain primary tumors, it is mainly indicated in metastatic disease and progression,” said Chung. “The protein is involved in the formation of immunosuppressive tumor microenvironments. Therefore, we found that our vaccine is much more effective at reducing metastasis, and not in reducing the growth of the primary tumors.”

“These findings are the most clinically relevant, as they closely model what could happen in real-life scenarios,” said Steinmetz. “For instance, a patient diagnosed with an aggressive cancer who undergoes surgery to remove their tumor may be at risk of recurrence and metastasis to the lungs. We envision that this vaccine could be administered post-surgery to prevent such recurrence and outgrowth of metastatic disease.”

Before the vaccine can progress to human trials, more comprehensive safety studies are needed.

“S100A9 is an endogenous protein within the lungs, and there isn’t a lot of data out there that demonstrate what happens when S100A9 is abolished,” said Chung. “We know that S100A9 is important in the clearance of pathogens, and future studies should better test whether reducing S100A9 levels decreases the patient’s ability to fight infections, especially in cancer patients who may have weakened immune systems.”

Future work will also explore the vaccine’s effectiveness when combined with other cancer therapies, with the aim of improving its efficacy against hard-to-treat cancers.

The post Curbing Lung Cancer Metastasis with Nanoparticle Vaccine appeared first on GEN - Genetic Engineering and Biotechnology News.

Broadcast Date: November 3, 2023
Time: 8:00 am PT, 11:00 am ET, 17:00 CET

Hydrogen/deuterium exchange coupled to mass spectrometry (HX-MS) is a valuable technique for analyzing the structural features and dynamic properties of individual proteins and large protein complexes. HX-MS can be used to study a wide range of structural properties including protein folding, ligand binding and allostery, and epitope mapping in the development of therapeutic antibodies. However, HX-MS is not routinely used in protein structure analysis because of data analysis challenges that limit its throughput and scope.  

In this GEN webinar, Dr. David Schriemer, University of Calgary, will present an innovative approach for applying HX-MS to protein analysis in biotherapeutics development. He will demonstrate a data independent acquisition-based HX-MS workflow that significantly reduces analysis times, enables the study of larger datasets, and paves the way for a standardized strategy for protein structure analysis. Dr. Schriemer will show how HX-MS can rapidly characterize drug-binding interactions using a 500-kDa mammalian kinase using affinity pulldowns.  

Key takeaways from the webinar include:

• Discovering the latest MS advances that benefit HX-MS technology.
• Learning about the implementation of data-independent acquisition for HX-MS.
• Learning how to use HX-MS to study drug binding interactions and higher-order protein structure dynamics.
• Understanding the data mining approach used to confirm peptide ID and authenticate, or even correct, MS1-based deuteration calculations.

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

Produced with support from:

David Schriemer, PhD
Professor
University of Calgary

The post Automated Protein Structure Analysis Using DIA Based Hydrogen Deuterium Exchange Mass Spectrometry appeared first on GEN - Genetic Engineering and Biotechnology News.

Carlsbad, CA—Durhane Wong-Rieger, PhD, president and CEO of the Canadian Organization for Rare Diseases and chair of a global alliance for patient organizations called Rare Diseases International, recalled a recent conference where he found himself speaking between panels with a patient advocate from Zimbabwe.

The woman, whom Wong-Rieger regards as one of the smartest and most involved patient advocates he knows, told him she would not go to any more sessions on cell and gene therapy because she didn’t want to hear about therapies that she or her patients would never get.

Wong-Rieger immediately realized the truth in her statement: many people who are in dire health conditions have no access to what may be a life-saving treatment.

“We really don’t have any rules for [cell and gene therapies] as we’re all saying this is the most amazing breakthrough in terms of therapies—truly lifesaving therapies,” said Wong-Rieger. “But the problem is we can’t give them to everybody. Unfortunately for us in this whole space, how do we get to doing what is the right thing?”

While Wong-Rieger doesn’t have the answer, he thinks that evolving ethics are at the heart of what will allow the field of cell and gene therapy get there.

A North Star

Ethics often gets a bad rap for being prohibitive, but for J. Benjamin Hurlbut, PhD, associate professor, School of Life Sciences, Arizona State University, that’s just plain wrong. Hurlbut believes that ethics is primarily about innovation and limits themselves can be sources of creativity and innovation.

“This is a domain where lives are at stake, and it makes this industry a different kind of industry than other industries because the stakes associated with the work, how the work is done, what the work means, and the name of the public goods the work has undertaken have a greater significance than in the automobile and smartphone industries,” said Hurlbut.

Tim Hunt, JD, CEO of the Alliance for Regenerative Medicine (ARM), has been mulling over the ethics of cell and gene therapy for months because, ultimately, this is the business of permanently altering people’s DNA or irreversibly transplanting cells.

“For too many of our patients—millions of people around the world—the status quo represents death or serious disability,” said Hunt. “No one runs out and takes gene therapy, a gene editing regimen, or cell therapy because they feel great and healthy. Patients are in difficult shape.”

Rob Perez, operating partner at the global growth equity firm General Atlantic, feels similarly about ethics, which he defines as a set of moral principles that helps one navigate challenging problems and situations.

“If we can have more conversations and come to more alignment on what an ethical code or ethical standards could be for the industry, it can help to be a north star on how we want to operate and how we want to make those very difficult decisions,” said Perez. “That’s always been a really important part of how I can deal with the most challenging questions, the most challenging decisions, and the most challenging complexities in operating a business.”

Value and accessibility

While the goal of many cell and gene therapies is to cure diseases and completely return a patient to full health, an incremental change in the patient’s health, which also can greatly affect a whole family, is understated. Somebody having to walk or sit for the rest of their time can be incredible in terms of that benefit.

Tay Salimullah, vice president, Global Head of Value and Access, Novartis Gene Therapies, was part of the team that led the first FDA-approved cell therapy, Kymriah, and is currently on a team working on a treatment for spinal muscular atrophy. He says defining patient success happens before one even begins to define value and economics.

“You have to actually understand the journey—the days, weeks, months, years—it takes families to try and get care,” said Salimullah. “It’s like a diagnostic odyssey where they can’t even actually then find out who’s going to treat them in what center. And that’s before even getting to the transaction of buying a gene therapy!”

For Salimullah, it’s all about democratizing access to gene therapies. Salimullah thinks carefully about how polarizing cell and gene therapy can be, especially regarding pricing.

“How can you have a $2-million gene therapy and leave babies to die?” asked Salimullah.

He believes in a self-imposed responsibility that looks for ways to find new opportunities where patients worldwide get access not only in the United States but in Europe and other environments. Salimullah thinks that the theme of democratizing access is dependent on finding the right people who can reinvent a playbook. But who is going to set that up? Will anyone take responsibility and apply it globally?

Janet Lambert, former CEO of ARM and now a consultant at The Densmore Group, believes the global democratization of cell and gene therapies will rely on public-private partnerships. That is a steep hill to climb.

“We’ve had such trouble successfully commercializing advanced therapies, and it is my view that getting it right and getting the economic base that’s necessary from the U.S. and Europe for these therapies is going to be absolutely essential to succeeding in global reach,” she said. “And we have a lot of work left to do there.”

The failed system of responsibility                             

Hurlbut thinks that it’s important to address whether the way of doing innovation in health for the public good is suited to the kind of innovation that is happening in cell and gene therapy. If it isn’t going to serve people as well as it can, then it’s no good.

“All the different stakeholders engage with the sector to ask pretty hard questions about whether the way business as usual is playing out is the best way for that business to play out,” said Hurlbut. “And if things change, some businesses may get broken. But that’s the way things should go if the question is about the broader purpose of this domain, which is to heal people, to treat people.”

According to Hurlbut, an obvious issue to address is pricing, because the sticker shock is so profound that it’s easy for people to protest such steep prices and blast the entire industry of cell and gene therapy as useless.

As he is not a health economist, Hurlbut doesn’t claim to have the answer. However, he said if the regimen is unsustainable for the long run such that society cannot benefit from the good things that its investments have produced, then it’s a failure. Hurlbut said that thinking about these kinds of questions—such as whether cell and gene therapy is economically sustainable—has ethical stakes.

“Is the right way to ask questions about that life in terms of healthcare costs saved, future economic productivity, or to count the various beings and pile them up and say, look, there’s value here?” said Hurlbut. “Maybe that’s the way that one has to convince some set of actors, but maybe that’s the wrong way to ask questions about children’s lives.”

Hurlbut goes one step further, suggesting that, depending on a particular society or government, the decision on whether to get treated or not could be taken completely out of the hands of the patient at the earliest of life stages, even before birth, for all sorts of reasons like cost-savings—the more people who are “cured,” the less of an economic burden on that society. Hurlbut brings up a situation for which he has unique insight—that of He Jankui and the IVF embryos that he gene-edited—noting that one of the central arguments for this infamous experiment that was undertaken in China a few years ago is that it’s a lot easier and a lot cheaper to do it in one cell than to do it in many.

Hurlbut thinks that thinking through this ethical problem highlights that with the system that gets put in place—the drug makers, the regulators, the insurance companies, the health systems—no singular actor is responsible, but instead, it’s the collective actions of the community put in place—and that’s where things can go wrong because it results in failures of responsibility, compassion, and recognition of what is at stake.

After all, there is a dark side to gene therapy, and not every company working on cell or gene therapy is thinking about how their technology may contribute to applications that they would never endorse and, even, abhor, such as genetic cleansing.

Changing the path of humanity 

Even in a world where accessibility and economics for cell and gene therapies get worked out ethically, there’s another set of questions lying in wait that are top of mind for Lambert. For example, if a person chooses to get treated with gene therapy and it reaches the germline, genetic changes will be made in the patient and possibly in their children and generations to come.

Similarly, who is responsible for whether a child with a disease will get gene therapy? Does it fall into the hands of the parents?

“One of the most profound conversations I had in my time at ARM was with a mom who had signed her child up for a safety study,” said Lambert. “And even though this was a very well-educated mom, she felt profound guilt about having done that and that her child was, therefore, ineligible to get a therapeutic dose, which in that particular case turned out to be different than the safety trial dose.”

When it comes to gene editing, Lambert thinks that a major challenge in deciding what is a disease, what’s worth preventing, and what needs to be prevented.

At the end of the day, cell and gene therapy is not about eliminating or customizing people—it’s about treating patients.

The post Meeting on the Mesa: Without Ethics, Cell and Gene Therapy Will Fail appeared first on GEN - Genetic Engineering and Biotechnology News.

Panelists:

Arpan Desai
Managing Director
NanoVation Therapeutics UK

Graham Hayes, PhD
Senior Scientist
NanoVation Therapeutics UK

Ben Knappett, PhD
Product Manager, LNP Solutions
Unchained Labs

Broadcast Date: November 8, 2023
Time: 8:00 am PT, 11:00 am ET, 17:00 CET

Lipid nanoparticle (LNP)-based mRNA technology enabled the rapid development of COVID-19 vaccines resulting in unprecedented interest in the technology’s potential. Many researchers approach the design issue via systematic optimization of lipidic components such as the ionizable lipid, PEG lipid, structural and helper lipids. However, these approaches are limited by the low-throughput and high cost of LNP preparation.

In this GEN webinar, our expert speakers will discuss strategies and tools for rapidly formulating and characterizing LNPs for drug discovery and development. They will share results from a collaboration between Unchained Labs and NanoVation Therapeutics UK to evaluate instrumentation for high throughput-controlled manufacture of LNPs at small scales and demonstrate how their findings will accelerate the creation of LNP-based medicines.  

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

Produced with support from:

The post Accelerating mRNA-LNP Formulation Screening for Genomic Drug Discovery and Development appeared first on GEN - Genetic Engineering and Biotechnology News.

Novo Nordisk (NVO) continued its year-long stock surge this week when it halted a Phase III trial early due to undisclosed efficacy results suggesting that its blockbuster adult type 2 diabetes drug Ozempic^® (semaglutide)—which shares the same active ingredient as its obesity drug Wegovy^® (semaglutide injection)—is also an effective treatment for chronic kidney disease (CKD).

Novo Nordisk announced an early halt to its Phase III FLOW trial (NCT03819153), designed to compare semaglutide with placebo in the progression of renal impairment in people with type 2 diabetes and chronic kidney disease. The company cited a recommendation from the study’s independent Data Monitoring Committee (DMC) following results from an interim analysis that were not shared in a press release announcing Novo Nordisk will begin closing the trial.

Results from FLOW are expected to be read out during the first half year of 2024, Novo Nordisk said.

Launched in 2019, FLOW enrolled 3,534 patients and has been conducted at more than 400 investigator sites in 28 countries. According to baseline data published August 31 in Nephrology Dialysis Transplantation, enrolled participants had a baseline mean age of 66.6 years, haemoglobin A1c of 7.8%, diabetes duration of 17.4 years, an estimated glomerular filtration rate (eGFR) of 47.0 ml/min/1.73 m2 (SD 15.2) and median urine albumin-creatinine ratio (uACR) of 568 mg/g (range 2‒11 852), with 68.2% of patients at “very high risk” for CKD progression.

The CKD market is projected to grow from $32 billion as of last year to $47.9 billion by 2032, at a compound annual growth rate of 4% from 2023 to 2032, Allied Market Research has projected.

Acing the Phase III trial helped Novo Nordisk maintain a rising stock price, with shares on Nasdaq Copenhagen climbing 5% on Wednesday, from DKK 650.10 ($92.49) to DKK 681.80 (an even $97), then another 4% on Thursday, to DKK 710.20 ($100.47). Novo’s American depositary receipts (ADRs) on Nasdaq in New York rose 6% Wednesday from $93.01 to $98.84, and another 1.5% on Thursday as of 12:49 p.m. ET, to $100.29.

Novo Nordisk has seen its shares rise 13% since October 3, when they closed at DKK 625.70 ($89.04), a day after the company won FDA approval for another drug with a kidney-related indication—Rivfloza^TM (nedosiran) injection, a once-monthly subcutaneous RNA interference (RNAi) therapy designed to lower urinary oxalate levels in children ages nine and older and adults with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function.

Novo’s ADRs have risen 14% from $87.78 on October 3.

Near doubling year-over-year

More impressively, however, Novo Nordisk shares have surged 45% since January, when they began the year trading at DKK 471 ($67.04)—and have soared 71% over the past 12 months, from DKK 398.60 ($56.73) on October 11, 2022. That surge has transformed Novo Nordisk market capitalization—the product of the share price and the number of outstanding shares—into the second highest in Europe behind Nestle, according to Morningstar. Based on that market cap, Novo Nordisk topped GEN’s A-List of Top 25 Biotech Companies of 2023, published in May.

U.S. investors have been even more bullish on Novo Nordisk as its ADRs year-over-year have nearly doubled, rocketing 88.5% from $52.19 on October 11, 2022.

The ADR and stock surges reflect growing patient demand for drugs indicated for diabetes—and especially weight loss, since semaglutide is also the active ingredient in Novo Nordisk’s obesity drug Wegovy.

Investors apparently agree with Novo Nordisk’s apparent conclusion that Ozempic, as with other GLP-1 receptor agonists, have “therapeutic benefits far beyond their original intended purpose, according to Emily Field, director, head of European Pharmaceuticals Equity Research with Barclays, as reported by Reuters.

During the first half of this year, sales of Ozempic jumped 58%, from DKK 26.384 billion (about $3.758 billion) to DKK 41.741 billion ($5.945 billion), after zooming 77% last year, to DKK 59.750 billion ($8.509 billion) from DKK 33.705 billion ($4.8 billion) in 2021.

Also benefiting from Novo Nordisk’s good Ozempic news is Eli Lilly, whose stock has increased 6% earlier this week, from $571.76 on Monday to $605.28 on Wednesday. Lilly markets the type 2 diabetes drug Mounjaro^® (tirzepatide), to which the company is working to add an approval as a treatment of adults with obesity, or overweight with weight-related comorbidities. Lilly has a rolling submission to the agency for approval of the obesity indication, and has reported positive results earlier this year from three Phase III trials: SURMOUNT-2 (NCT04657003), SURMOUNT-3 (NCT04657016) and SURMOUNT-4 (NCT04660643).

Mounjaro has already reached blockbuster status, with January–June 2023 sales of $1.548 billion, multiples of the $16 million racked up in the first half of last year (all of it in June 2022, the month Mounjaro was commercially launched). For all of last year, Mounjaro generated $482.5 million in sales according to Lilly.

Morningstar has projected that sales of Ozempic will rise to earn $19.3 billion in 2027 and about $20 billion in 2030. Lilly’s Mounjaro^® (tirzepatide) future sales have been pegged even higher at $21.2 billion in 2027, while Wegovy, a next-gen once-weekly injection version of semaglutide approved in 2021, is projected to earn $12.5 billion in 2027.

Dodging a Bullet

Novo Nordisk dodged a proverbial bullet October 2 when the U.S. Patent and Trademark Office (USPTO)’s Patent Trial and Appeal Board (PTAB) denied an inter partes review (IPR) request by Mylan Pharmaceuticals, a generic drug company owned by Viatris, challenging Novo’s two key composition of matter patents for semaglutide, Nos. 8,129,343 and 8,536,122.

IPRs are designed to review the patentability of one or more claims in a patent based on two of the three patentability criteria, novelty and non-obviousness. In challenging the patents of Novo Nordisk, Viatris hopes to accelerate the arrival to market of the first generic version of Ozempic.

“VTRS’s arguments against the patents appeared weak, & we expected NVO to win,” Jefferies equity analyst Akash Tewari and colleagues wrote October 2 in a research note.

Two days later, however, the PTAB granted a separate IPR request to review the patentability of 10 claims within a third semaglutide patent, No. 10,335,462, covering dosing regimens: “We are persuaded that Petitioner has demonstrated a reasonable likelihood that it would prevail with respect to at least one claim challenged in the Petition,” according to the decision, written by Administrative Patent Judge Susan L.C. Mitchell.

While Novo Nordisk has vowed to vigorously defend the ‘462 patent, Tewari said the setback for the company isn’t as significant as it could have been.

“We don’t think this is a key patent as it only covers Ozempic, & the key claim is treating T2DM pts [type 2 diabetes patients] with a dose of 1.0 mg weekly,” Tewari and colleagues noted, citing the dosage of up to 2.4 mg weekly used in another clinical study—the Phase III SELECT trial (NCT03574597), a placebo-controlled, 17,609-participant study designed to assess whether semaglutide can reduce the risk of cardiovascular events in patients who are overweight or obese, with prior cardiovascular disease.

Two other challenges remain for Ozempic. Novo Nordisk is seeking to stop compounded versions of Ozempic as well as Wegovy from reaching the market. The company has sued four compounding pharmacies led by Brooksville Pharmaceuticals in U.S. District Court for the Middle District of Florida, Tampa Division, arguing that the compounded versions were never approved by the FDA. U.S. District Judge William F. Jung dismissed the suits on October 5, but Novo Nordisk has said publicly it plans to refile them.

Another challenge looming is Medicare drug-price negotiation, with Cantor Fitzgerald analyst Louise Chen telling CNBC in August that the drug may be among those chosen by the federal agency for discussions: “Ozempic is going to be the biggest one that people are going to watch really closely in the second round of negotiations.”

Leaders & Laggards

• Akero Therapeutics (AKRO) shares have plunged 70% over two days after the company disappointed investors with results from its Phase IIb SYMMETRY trial (NCT05039450) assessing lead product candidate efruxifermin (EFX) in patients with compensated cirrhosis (F4) due to NASH. EFX missed the study’s primary endpoint of achieving a one-stage or better improvement in liver fibrosis without worsening NASH, following 36 weeks of treatment with EFX vs. placebo. However, Akero cited a positive trend of 22% and 24% of the 28mg and 50mg EFX-treated groups, respectively, experiencing at least a one-stage improvement, vs. 14% for placebo. “We believe EFX has the potential to show additional improvements for patients after the long-term follow-up period is complete at Week 96,” Akero president and CEO Andrew Cheng, MD, PhD, stated. Shares plummeted 63% from $48.54 to $18.15 on Tuesday, and fell another 19% on Wednesday, to $14.68.
• Tempest Therapeutics (TPST) shares soared into the stratosphere, zooming more than 4,000% from 24 cents to $9.77 on Wednesday, after the company released updated positive results from an ongoing global Phase Ib/II clinical trial (NCT04524871) in which the lead program of the peroxisome proliferator-activated receptor alpha (PPAR⍺) antagonist TPST-1120 showed clinical superiority in multiple endpoints when combined with Tecentriq^® (atezolizumab) and Avastin^® (bevacizumab) in a randomized comparison to the two Roche (Genentech) marketed cancer drugs in the first-line treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC). Data showed a confirmed objective response rate of 30% for the TPST-1120 triplet arm versus 13.3% for atezolizumab and bevacizumab. Duration of response has not yet been reached.
• Teva Pharmaceutical Industries (TEVA) American depositary shares rose 2.5% over two days while its shares traded on the Tel Aviv Stock Exchange inched up about 1%, from ILS 3,608 ($909.03) to ILS 3,631 ($914.87) Wednesday, after the Israeli-headquartered drug developer said Tuesday it did not foresee a “meaningful” impact from Israel’s war against Hamas. Teva said its revenues in Israel last year accounted for approximately 2% of its $14.9 billion in global revenues, while production in Israel constituted less than 8% of its total global production in U.S. dollars. Production remains “largely unaffected,” the company added. “As an Israeli company we condemn this appalling assault and Teva stands with Israel in this time of great loss and challenge,” Teva declared.
• Ventyx Biosciences (VTYX) shares nosedived 37% over 2–1/2 trading days despite reporting positive results from a Phase II trial (NCT05156125) assessing the oral S1P1 receptor modulator VTX002 in moderate-to-severely active ulcerative colitis (UC). Ventyx reported that 28% of patients on the 60 mg dose and 24% of patients on the 30 mg dose achieved the trial’s primary endpoint of clinical remission at Week 13 compared to 11% of placebo But investors appeared unimpressed since Ventyx is trying to compete with Bristol-Myers Squibb, whose UC drug Zeposia^® (ozanimod) won FDA approval in 2020, and Pfizer, whose UC candidate etrasimod is under FDA and European Medicines Agency review. Shares skidded 26% Tuesday, from an even $30 to $22.22, slipped 9% on Wednesday, to $20.25, and fell another 7% to $18.84 Thursday as of 12:30 p.m.

Alex Philippidis is Senior Business Editor of GEN.

The post StockWatch: Novo Nordisk Shares Soar as Ozempic Aces Phase III CKD Trial appeared first on GEN - Genetic Engineering and Biotechnology News.

Carlsbad, CA—The timing of the Cell & Gene Meeting on the Mesa appears to have been prearranged with the help of a crystal ball. Members of the cell and gene therapy field are anxiously awaiting the FDA’s review of three submissions before the end of 2023: two treatments for sickle cell disease—exa-cel (Vertex and CRISPR Therapeutics) and lovo-cel (Bluebird)—as well as Bristol Myers Squibb and 2Seventy Bio’s Abecma for earlier multiple myeloma.

The sector is at an inflection point. There’s a lot of excellent science and exciting clinical results. Still, it remains to be seen whether that will translate into commercial success—a major focus of this week’s Alliance for Regenerative Medicine (ARM) conference. 

Regulatory approval

All eyes, therefore, are on Nicole Verdun, MD, the new permanent director of the FDA’s Office of Therapeutic Products (OTC), which is within the Center for Biologics Evaluation and Research (CBER). Verdun’s plate has a healthy serving of cell and gene therapy clinical trials for rare and serious diseases, which typically do not fit the testing paradigm of a randomized clinical trial. According to Verdun, who will be working hand in hand with CBER director Peter Marks, MD, PhD, the key to the approval of cell and gene therapies for conditions with just a handful of patients is a mix of communication and regulatory flexibility.

“We have INDs open for diseases where there are 11 patients in the United States,” said Verdun. “There needs to be increased communication earlier on in the development process, and there has to be consideration for the disease, the benefit-risk for how rare it is, and we have to do what we can to partner to get more of these therapies to patients that need them.”

To get right at this, Verdun highlighted the “Support for clinical Trials Advancing Rare disease Therapeutics” (START) Pilot Program. Three chosen START participants must be sponsors of cell and gene therapies for rare diseases and serious conditions currently in clinical trials under an active Investigational New Drug Application (IND). These participants will be able to receive regular advice and ad hoc communication with FDA staff to talk about product-specific development issues, such as clinical study design, choice of the control group, and fine-tuning the choice of the patient population. START will begin accepting applications between January 2 and March 1, 2024. 

Manufacturing and commercialization

 As more cell and gene therapies begin to move into the clinic, there is growing attention on manufacturing, which may be the major bottleneck for creating commercialized products.

Automation and artificial intelligence (AI) will be major disruptors to the manufacturing and commercializing cell and gene therapy. The efforts made by Cellares with its Cell Shuttle to integrate batch processing and automation into the assembly process serve as evidence of this. But automation and AI will not be enough.

According to Ann Lee, PhD, chief technical officer at Prime Medicine, there are three key factors to developing commercial-grade manufacturing. The first is picking the right people, because getting a cell and gene therapy program into the clinic requires a breadth of expertise that will likely not be found in a single individual. The second is data infrastructure, because to generate data that will be submitted for an IND or BLA submission, processes need to be in place where it is retrievable, tracked, and analyzed. Third, Lee said that regardless of going the internal or external route, the process needs to be transparent because no cell or gene therapy will be approved if the manufacturing process is a black box.

Some key factors go into choosing to partner with an external CDMO for manufacturing or bringing it in-house, often touted as the best way to control one’s destiny. While many have approached the manufacturing of cell and gene therapies with the view to putting all their manufacturing capabilities into the hands of partner CDMOs, some have decided to take this on to various degrees to gain increased control of their medicine’s destiny.

For cell therapies, some of this may come down to whether a company’s approach uses allogeneic or autologous cells. Sumit Verma, senior vice president of Global Strategic Manufacturing at Iovance Biotherapeutics, said that, while there is a lot of allogeneic work being done and CAR T having that success rate, autologous cell therapy has its place as a potentially unrivaled personalized medicine but is incredibly challenging from a logistics side. “For the patient’s benefit, being able to manufacture [an autologous cell therapy] batch is a key concept that I think you’re going to see a lot more maturity next year,” said Verma.

With two autologous cell therapy, using patient-specific tumor-infiltrating lymphocytes and peripheral blood lymphocytes (PBL), Iovance has taken an approach to investing in both their own manufacturing capabilities, as evidenced by their recent investment in establishing the Iovance Cell Therapy Center (iCTC)—a 136,000-square-foot facility in Philadelphia.

While Intellia Therapeutics will also be opening a new manufacturing facility in Waltham, Massachusetts, in 2024, chief business officer Derek Hicks said that in this market environment, he wouldn’t be surprised if there are more deals featuring a shared partnership between manufacturing and smaller biotechs.

“When you think about manufacturing, it’s not just that shared risk,” said Hicks. “It is how can you work with someone that actually helps you accelerate because we’re trying to get these products to patients. The research is moving very quickly, so how do you ensure that manufacturing doesn’t stop you from bringing things forward? These are the things that we all need to think about.”

Healthcare systems

Bob Smith, senior vice president of the Global Gene Therapy Business at Pfizer, said a lot of his concern for getting cell and gene therapies commercialized is related to the healthcare systems in the U.S. and abroad.

“A lot of healthcare systems have a negative innovation bias in the way that they evaluate and value the innovations that our sector is developing,” said Smith. “No individual company is going to be able to overcome this, and I think we need to think about how we communicate not just with the healthcare systems and how they evaluate not just the regulatory aspects, but now really the value of what we’re bringing to patients.”

For example, Smith points to some European markets where sometimes there isn’t a price approval for a year and a half after the regulatory approval.

“Think about the burden that is on small midsize companies that don’t have a balance sheet like [Pfizer does],” said Smith. “We can absorb that financial hit, but it’s going to put a tremendous financial strain on capital-intensive companies, and we need to really think through how we can change that paradigm to be much more efficient, principally for the benefit of patients but also, quite frankly, for the sustainability of the sector.”

Phil Cyr, senior vice president at Precision Value & Health, said that historically, a lot of payers and health technology organizations have been very focused on cost-effectiveness, but that they’ll also be looking at the budget impact and affordability, especially as cell and gene therapy begin to move into more prevalent diseases, which he believes will happen. Cyr thinks that the way to overcome this is by developing an evidence base to discourage people from thinking about sticker price and more towards long-term value.

“How do you go to a payer with a three to four-year window and make them understand that [gene therapy] will benefit them?” said Cyr. “I can think of one payer that actually built a model to figure out how long they needed to keep that member in their plan to recoup the money.”

For these reasons, organizations like Express Scripts and Cigna’s Embarc will play a key role in the future of gene therapies by helping protect customers from the high cost of gene therapy drugs and ensure access for those who need them.

 Expectations for 2024

Much is riding on the cell and gene therapy submissions that are due to be reviewed by the FDA before the end of this year. If they are successful, its possible that there will be a change in sentiment within the investor community—not to mention patients.

Next year, the Cell and Gene Therapy Meeting on the Mesa will move to Phoenix, Arizona, as the conference has maxed out its current capacity at the Park Hyatt Aviara Resort in northern San Diego. If the FDA approves these initial submissions, the new venue will likely be filled in 2024. But what if they’re not approved? All it takes is one bad batch that will reflect poorly on the entire industry.

As regulatory submissions and clinical data trickle in, there has to be a high standard. But standardization will not be achievable by a single business entity or the FDA alone. This new and evolving field will require organizations like ARM to unite different voices. That’s exactly what’s happening right now at the Cell and Gene Meeting on the Mesa.

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Carlsbad, CA—Across the board, biotech investing in 2023 has seen a retraction from the high levels seen the past three years: venture investment has dropped and companies large and small have lost value. However, that doesn’t mean that biotech investors have lost interest or abandoned ship. In fact, with the FDA reviewing submissions for three cell and gene therapies in Q4, investors are looking beyond the discovery and development phase and into the manufacturing and commercialization of these potentially revolutionary medicines—a theme that has taken hold at the 2023 Cell and Gene Meeting on the Mesa.

To get there, cell and gene therapy companies will have to do more than fly by on the seat of their pants, hoping to just live another day. Instead, there’s a sentiment amongst investors that now is the time to show a vision for the long run if biotech hopes to have financial support to carry them through until the headwinds die down and into the tailwinds for smooth sailing. 

Is this the new normal?

According to Dynamk Capital’s market analysis, the size and count of deals—mergers and acquisitions (M&A) and initial public offerings (IPOs)—have dropped from the 2020 to 2022 levels through the pandemic. But with three quarters complete in 2023, their analysis shows that the industry numbers are on par with 2018 and 2019 levels, perhaps even higher. Beyond some outliers such as Danaher’s acquisitions of Aldevron and Cytiva as well as the Thermo-PPD deal, Daniella Kranjac, founding partner and managing director at Dynamk Capital, said the trend for deals is pretty healthy.

While recent transactions aren’t pulling in deals of 20x revenue as seen during the pandemic, they’re also not at the 3–6x revenue multiples seen in 2018–2019. The industry is at the “new normal,” she said, which is in the 10–15x range.

Valerie Dixon, managing director at Morgan Stanley, says it is less a “new normal”, and more of a reversion to the historical mean. It is foolish to hope for the same “irrational exuberance” of the market to return to pandemic levels and that things won’t change back to how they were in 2020 and 2021, she said.

“They’re not going to be saved by a white knight and get 15x as much revenue for their company. That’s not happening!”

Kicking the can down the road

While some investors, board members, and founders have been trying to stay afloat in the turbulent economic climate, Dixon said the perception that they can just kick the can down the road and stretch their cash for another two to four quarters is irrational, even in the context of recent geopolitical events—Russia and Ukraine and now Israel and Palestine.

“You can’t manage your balance sheet anticipating World War III,” said Dixon. “You need to be managing your own business for a two to three-year timeframe, not for next quarter or making that month’s quota.” Instead, Dixon believes that managing a biotech business today requires creating long-term, enduring, profitable growth. That’s what funders think is most credible.

“When you can tell a story about how you’re investing for long-term growth, then [the investors] will be there for your expansion capital or your growth capital when you need it,” said Dixon. “If they take that long-term mindset with you, that means that you can have confidence that they’re going to have capital that’s going to grow with you along the way. It’s not growth at any cost; it’s making sure you’re doing responsible growth and you’re hitting… milestones that will get you to that next inflection point.”

While Sean Mackay, Operating Partner at Casdin Capital, is excited about the numerous companies with great products in great markets, he won’t invest in a company if they can’t support their own operating expenses. For Mackay, it comes down to the return on investment from capital.

Consistency is key, Mackay insisted. He wants to know that a prospect’s revenue isn’t random and that a particular move is devoted to a big market that the company is creating or disrupting, which is harder to do. A company’s capital-raising process has to increase the number of shots on goal and, thus, increase the probability of raising the money. To succeed, Mackay says companies need to be creative and expand their funnel instead of just hopping to the next shiny thing.

To IPO or not IPO

Although there have been signs of life for investing in healthcare and biotech—nine deals so far in 2023 (eight in biotech)—today, only three are trading around issue price. Some 2021 biotech IPOs, Dixon notes, are trading as low as 85% below the original issue price.

“Just because you’re going public doesn’t mean everything’s great,” said Dixon, who has led Morgan Stanley’s efforts in life sciences tools and diagnostics. “You still have to pay attention to aftermarket performance… and not just be the first one out of the gate. Be consistent in execution and a good steward of the capital that you raise. Maybe they [went] public too early, took their eye off the ball, or any number of factors—all those things play into the success of an IPO.”

Kranjac’s guidance to founders trying to get term sheets done in this market environment and the near future is to make sure they are thinking about who they bring to the table— board members and investors who understand the market and can be helpful in terms of forging additional relationships, whether for investments, operations, or talent.

There is no magic wand to secure a deal sheet for financing, but Kranjac shared the advice she can give the founder of an early-stage company: although they may have the luxury of being pre-revenue and not having reportables on a monthly or quarterly basis, they should be raising as much money as possible.

“In this environment, the guidance that we’re giving our portfolio companies, and even companies that we’re looking at going forward, is don’t wait,” said Kranjac. “There were a number of folks that early in the year said, ‘We’re going to wait until the fall when the market’s better or until [JP Morgan] 2024, when things are going to be great. Don’t wait!”

As to how to value a company, Mackay said that during the 2019 and 2022 period, research analysts might have understood the liquidation value for a sale. But when there’s no M&A activity, that number is more difficult to calculate. The huge push by big pharma to invest in new therapeutic modalities like cell and gene therapies is evidence, according to Mackay, that the industry’s “tailwinds” appear to be very strong.

Dead cells don’t cure cancer

A major early theme of the 2023 Meeting on the Mesa has been manufacturing and commercialization. Along these lines, while the panelists are all excited about the development of cell gene therapies and the enabling tools that go along with them, they’re keeping a close eye on companies involved in manufacturing and commercialization.

Kranjac agreed that bioproduction is exciting because there are going to be many such medicines. And those are exactly the types of companies, like RoosterBio, Curi Bio, and CellFE, that Dynamk has been adding to its portfolio.

“You can’t take your eyes off the ball on the manufacturing process and the tools that help with potency, stability, purity, and quality control—dead cells don’t cure cancer,” said Dixon. “When there are huge acquisitions with outsourced manufacturing and you start seeing the Thermo Fishers and Danahers making multi-billion-dollar acquisitions in the space to have capacity for cell gene therapies, that’s a wake-up call.”

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Panelists:

Sascha Losko
Director of Product Management
LabVantage Biomax

Jeff Vannest
Senior Director of Knowledge Management
LabVantage Solutions

Nusreth Baig
Head of Sales, North America
TCG Digital

Broadcast Date: November 2, 2023
Time: 8:00 am PT, 11:00 am ET, 17:00 CET

Recent advances in automation and digitization are changing how drug research and development labs are structured and run. The Laboratory of the Future will be more data-centric, collaborative, efficient, and adaptable than ever before enabling R&D teams to accelerate innovation, reduce time-to-market, and address research challenges more effectively. To keep up, R&D professionals have to embrace a range of new digital tools and automated solutions that they can use to adapt their workflows, protocols, and processes to a dynamic and rapidly evolving research landscape.

In this GEN Learning Lab, you’ll hear from a panel of experts about the technologies and strategies that will drive the transformation of the drug discovery labs. They’ll discuss how automation and digitization will help scientists optimize production, manage projects and tasks, and enable discovery at every stage of drug development.

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

Produced with support from:

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