Eisai, Biogen's Alzheimer's med Leqembi turned down in Europe—but analyst says it's merely a 'delay'

Although patients on Leqembi scored better than placebo on the Clinical Dementia Rating Scale Sum of Boxes—an index used to measure dementia severity—the difference between the two groups was “small,” the EMA noted in a fact sheet.

Ultimately, the agency ruled that the positive effects of Leqembi on delaying cognitive decline “do not counterbalance the risk of serious adverse events.”

Unlike its controversial predecessor Aduhelm, Leqembi didn’t stir up much debate around its approvability in the U.S. As Biogen has stopped making Aduhelm, Leqembi has become a key part of the company’s plan for a business turnaround.

 Scientists at UC San Diego have developed a machine learning algorithm to simulate the time-consuming chemistry involved in the earliest phases of drug discovery, which could significantly streamline the process and open doors for never-before-seen treatments. Identifying candidate drugs for further optimization typically involves thousands of individual experiments, but the new artificial intelligence (AI) platform could potentially give the same results in a fraction of the time. The researchers used the new tool, described in Nature Communications, to synthesize 32 new drug candidates for cancer. 

  Experimentally induced hypoxia has the potential to serve as a research tool. Hypoxia could be used as a human disease model mimicking or inducing the pathological responses observed in certain diseases. A potential advantage of the approach is that hypoxia exposure can elicit physiological responses in isolation from common confounding variables, in controlled and measurable amounts, with graded doses, and safely in otherwise healthy individuals. Furthermore, hypoxia could be utilized to validate potential treatment targets and pathways that are regulated through oxygen. 

In this week's industry update we take an in-depth look into the future of biotechnology in 2024 . 

The increase in the number of FDA submissions and approvals of cell and gene therapies poses a challenge for biopharma manufacturing. The supply chain must be able to keep up with the demand for therapies manufactured using manual and labor-intensive processes.

Last month in Miami, cell and gene therapy (CGT) professionals gathered at Phacilitate’s Advanced Therapies Week to discuss manufacturing needs for one particular cell therapy that’s growing in popularity: CAR T cell therapies.  

Rupa Pike, senior director and head of field scientists and strategic alliances for cell therapy at Catalent, told BioSpace she noticed several themes emerge at the meeting. First, she said, attendees were more excited than last year about increased investment in CGT. The global CAR T cell therapy market was valued at $2.75 billion in 2022 and expected to grow at a compound annual rate of 23.32% through 2030. In addition, advances in manufacturing technologies are allowing companies to develop more efficacious assays with a shorter turn-around time, Pike said.

Moving away from viral vectors to get genetic material into cells was another big talking point in Miami, according to Josh Ludwig, global director of global operations for ScaleReady, as was the shift in focus from autologous to allogeneic approaches, which have the potential to reduce costs by providing off-the-shelf varieties of CAR-T therapies.

“A focus in the industry for 2024 and beyond is to develop allogeneic therapies with durable responses and eliminate the use of virus, lentivirus and retrovirus in favor of nonviral gene editing techniques,” Ludwig said.    

He added that collaboration within the industry will be key to create simple, standardized production processes. He said that the consensus at the meeting was that companies would share their approaches and successes with the field.

This would be a change, Ludwig explained, as companies have recently been very protective of their production processes—more so than when he started in the industry about 10 years ago. But he believes there is a middle ground where some basic principles about how to manufacture these cell therapies can be defined and shared openly.

“What ScaleReady plans to do and the CAR-T field is more receptive of in 2024 is trying to standardize the way we manufacture therapies,” Ludwig said. “There are building blocks to making those cells, and it should be standard that all companies use those building blocks, and each put their own unique target on them.”

Moving Toward Allogeneic, Off-the-Shelf Options

ScaleReady, whose manufacturing platform brings together cell culture, cell activation and expansion, gene editing and cell processing technologies, is partnering with Luminary Therapeutics and its allogeneic Gamma 2.0+ platform, Ludwig told BioSpace.

The partnership will develop a new CAR-T platform using a nonviral gene editing approach called a novel transposon-transpose system, Ludwig said. Partnering with ScaleReady can help Luminary generate good clinical data before they raise money and build a manufacturing facility, he added.  

“What Luminary is looking to do is create an allogeneic bank where cells from one healthy donor can generate thousands of doses and and drive down the cost of treatment, which can be as high as $500,000,” Ludwig said. 

In addition, he continued, “allogeneic therapies will provide more supply chain and scheduling stability to manufacturers and sponsors,” by producing more doses within a single lot release.

However, it remains to be seen if pharmaceutical-scale batches in the hundreds of thousands of doses can be produced by allogeneic cell therapy developers. Large-scale downstream processing and formulation and the filling of large quantities of cell product into drug product containers remain challenges for allogeneic manufacturing.

As allogeneic CAR-T manufacturing evolves, Ludwig said he sees a future where allogeneic and autologous cell therapies coexist to meet the needs of different patient populations. “When using modular, scalable and standardized tools and technology, the exact same facility and clean room layout is amenable to both autologous and allogenic cell therapy manufacturing,” he said.

Digitizing CGT Manufacturing to Reduce Cost

For the past two years, Ori Biotech has been giving industry partners such as Inceptor Bio, adtherabio and CTMC access to its proprietary CGT manufacturing platform prior to its launch later this year. Ori’s Lightspeed Early Access Program (LEAP) partners have been doing feasibility testing of the digital platform to accelerate progress toward scalable production of cell therapies.

Jason Foster, CEO of Ori, told BioSpace that the platform basically has three parts: a bioreactor system that physically produces cell therapies, an automation component to complete steps in the manufacturing process currently done manually, and a platform for real-time data analysis. He described this automated, digital approach as “industry 4.0” with the ability to capture data in real time.

Ori will be doing feasibility testing with 10 to 20 customers in 2024 and plans to deliver the product commercially toward the end of the year, Foster said.

“I’d like to see the industry make a commitment to adopting digital technologies at scale so that we can produce high-throughput products for a lot of patients,” Foster said. He added that he hopes the cost of producing these therapies will be significantly reduced over the next few years using platforms like the one Ori is developing.  

Working on such new platforms will require new skills. Last year, the Alliance for Regenerative Medicine published a report that found the CGT workforce lacked the necessary technical skills in development and manufacturing. The workforce also lacked production skills, such as artificial intelligence (AI) and automation.

In its report, the organization said that education should include not just basic science but also information technology, AI and automation, data management and analysis and programming. Certificate programs could strengthen the skills of the current workforce to support the CGT sector until more workers are trained, the report said.

 How Cell and Gene Therapy Manufacturing Will Evolve in 2024 | BioSpace 

In this week's industry updates this article from Federal News Network explains the DoDs new aims to capture small business. 

Over the past decade, the number of small businesses in the defense industrial base has decreased by 40%. With the first-ever National Defense Industrial Strategy out, the Pentagon wants to turn things around.

The recently awarded defense industrial base consortium agreement, for example, will allow industry partners, including small businesses and non-traditional contractors, to work with the Defense Department on defense supply chain technologies projects and potential research through prototype development initiatives.

“One of the things we want to look at is making sure that we are more approachable for small businesses,” Danielle Miller, acting deputy assistant to the Secretary of Defense for Industrial Base Resilience, said during the Washington Technology event on Feb. 16.

“They can come into the system and not be as overwhelmed by the FAR process. The goal is to make sure that we have access to new ideas as quickly as possible so we can bring them in and drive innovation through the defense industrial base. So we found the [other transaction agreements] are very useful for that because you come into the consortium, and we can take ideas and bring them to fruition faster.”

There are currently no fees to join the consortium, reducing the barrier of entry for businesses. The consortium, however, reserves the right to introduce fees of up to $250 at a later date, which will provide members with access to membership meetings, additional consortium collaboration and industry events.

Additionally, the defense production act program office issued a funding opportunity announcement (FOA) to solicit proposals for production technology projects. It allows the industry to submit white papers at any time. While companies can choose the topic of their white papers, it should align with one of the DPA’s areas of focus, including sustainment of critical production, commercialization of research and development investments and scaling of emerging technologies.

“If you have an idea, you can just write a white paper and submit it, and then we’ll evaluate it against our criteria and we can pick it up from there,” Miller said.

Miller said her office has an industry engagement team that has been doing a series of listening sessions to gather industry’s feedback.

“We’ve also been doing some one-on-one meetings with industry so they can provide us with information. Two weeks ago, I met and talked to the different members of the agency and international partners about their thoughts on the implementation plan as well,” Miller said.

Miller’s office is currently working on the implementation plan for the recently released strategy, which will contain metrics, milestones and specific steps DoD plans to take to foster a more resilient defense industrial base.

The implementation plan will be classified, and it is unclear if any of those details will be publicly available.

“We are in the process of building it. The final product will be classified for operational security reasons. But we will be working through different venues to talk about specific components with the appropriate audiences.” Miller said. “In some cases, if we need more feedback, we’ll bring in specific individuals who are cleared at the appropriate level to actually get more feedback from them.”

DoD has various authorities and tools available to move forward with defense industrial base initiatives under the Defense Production Act. While the department has largely relied on grants and procurement commitments, it is now exploring loans and loan guarantees.

While the specific metrics remain unclear, the success of the defense industrial base will be assessed based on its growth in the next three to five years, the investments made, and factories built.

“I think the [Defense Production Act] investments are a good indicator of what we’re doing,” Miller told Federal News Network on the sidelines.

 Pentagon wants to be ‘approachable’ for small businesses (federalnewsnetwork.com) 

In this week's industry updates, we look at the role of AI in the BioPharma world.  

In biopharma R&D there is growing momentum around the use of Generative AI, the deep-learning algorithms capable of distilling complex knowledge into easily digestible summaries. But so far companies have been relatively modest in their ambitions for the technology. Although applying GenAI discretely within individual departments makes sense for many use cases, the greater opportunity is to harness it across all functions—as a super decision intelligence tool, bringing all aspects of the R&D strategy together. 

The Unique Role GenAI Can Play 

A subset of artificial intelligence, GenAI can very rapidly distil key information and insights—via machine learning—from vast knowledge banks and create new output from it which is intuitive and easy to digest. In drug discovery, it can be used to harness smart, mass-scale data analytics in a reliable and accessible way.  

It can cost anywhere between $2.5 billion and more than $6 billion to bring a novel drug to market today given the high risk of failure, especially as the complexity of therapies grows. The challenge is to determine those opportunities worth pursuing, based on everything important that is already known about that field.  

The problem is how to get to those insights reliably and efficiently. Published research and other texts may contain rich knowledge, but largely all of this content remains un-curated and daunting in scale. Cause-and-effect-like relationships may be abundant across the available sources, for instance, but are generally difficult to pinpoint, connect, and analyze. Targeted use of AI makes it possible to capture and link findings so discovery teams can infer new meaning and insights.  

In one scientific study, for instance, researchers might have examined how a specific drug triggers the activation of a particular protein. Concurrently, a separate study has highlighted that this activated protein is linked to the onset of hypertension. It is only once these discoveries are connected that a potential hypothesis emerges: in this case, that the drug in question might pose a risk for inducing hypertension.  

The powerful enabler, thanks to GenAI, is the ability to structure and analyze valuable data that up to now has been locked in text. That could be from internal archives and/or from millions of scientific research articles, in combination with all the other structured data sources including transcriptomics and proteomics.

 (GenAI’s Real Potential in Biopharma: As a Cross-Function R&D Assistant (bio-itworld.com) 

In this week's industry update we look at the fiscal spending on contract awards in the FY23'. 

A HigherGov analysis of government contracting activity showed that federal contracts awarded in fiscal year 2023 reached a record high of $765 billion, reflecting a 9.5 percent growth from FY 2022.

The market research company said Wednesday the increase was driven by the exercise of options associated with F-35 fighter jet production, rebound in construction spending and direct and indirect awards related to weapons supply in support of the war in Ukraine, among other factors. According to the report, contract awards at the Department of Defense rose by 11.5 percent from $422 billion in FY 2022 to $470 billion in 2023, accounting for 61 percent of total federal contract awards in FY 2023. The Navy saw the largest jump in contract awards in 2023, recording $154 billion. HigherGov attributed the growth to aircraft manufacturing, engineering services, shipbuilding and repair and navigational equipment. The last fiscal year witnessed a slight increase in the number of contractors receiving DOD awards, rising from 37,057 contractors in FY 2022 to 37,092 vendors in FY 2023. The value of contracts awarded by civilian agencies also rose 6.3 percent to $295.1 billion in FY 2023, up from $277.5 billion in FY 2022. HigherGov noted that the increase in federal spending on computer software and hardware has been consistent in the past decade. Software and hardware contract awards hit $80 billion in FY 2023, up from $75 billion recorded in the previous fiscal year.

Source:  Report: Federal Government Awarded Record $765B in FY 2023 Contracts - GovCon Wire 

This week's industry updates scientist have begun folding DNA to better understand diseases. 

"Researchers have used DNA origami, the art of folding DNA into desired structures, to show how an important cell receptor can be activated in a previously unknown way. The result opens new avenues for understanding how the Notch signaling pathway works and how it is involved in several serious diseases." 

 Karolinska Institutet. "DNA construction led to unexpected discovery of important cell function." ScienceDaily. ScienceDaily, 18 January 2024. <www.sciencedaily.com/releases/2024/01/240118122210.htm>. 

This week's industry update is on a team of scientist create a biorobotic heart. 

"Combining a biological heart and a silicone robotic pump, researchers created a biorobotic heart that beats like a real one, with a focus on a valve on the left side of the heart. The heart valve simulator can mimic the structure, function, and motion of a healthy or diseased heart, allowing surgeons and researchers to demonstrate various interventions while collecting real-time data."

Cell Press. "A beating biorobotic heart aims to better simulate valves." ScienceDaily. ScienceDaily, 10 January 2024. <www.sciencedaily.com/releases/2024/01/240110120213.htm>. 

In this weeks industry update, we take a look at how AI is revolutionized the Bio-Tech industry.        

Commentary contributed by Xavier Barril, Ph.D., Chief Scientific Officer of Gain Therapeutics 

Driven by advancements in technology and data accessibility, computational methods and artificial intelligence (AI) have seen remarkable growth this past decade. This surge has ushered in a new era of problem-solving across a plethora of industries and domains. In particular, the field of drug development is undergoing significant transformation as a result of these advancements, offering solutions to longstanding challenges encountered by the industry. 

Unmasking allosteric-binding sites on the 90% of currently deemed “undruggable” proteins is one area that’s tapping into supercomputing for drug target discovery. By targeting and binding a small molecule to an allosteric site on the protein (a site other than the active, functional site), allosteric modulation can trigger a conformational change in the protein's structure, creating therapeutic possibilities when it is implicated in disease. This conformational change can either enhance (positive allosteric modulation) or inhibit (negative allosteric modulation) the protein's activity to either correct or disrupt its function, and potentially other molecular changes, like stabilizing the protein, that could be beneficial in targeting misfolded proteins.   

 Power of Supercomputing and AI: Revolutionizing Allosteric Drug Discovery (bio-itworld.com) 

This week's industry update is on the development of new brain mapping research created by scientist. 

Researchers have created a complete cell atlas of a whole mammalian brain. This atlas serves as a map for the mouse brain, describing the type, location, and molecular information of more than 32 million cells and providing information on connectivity between these cells. continued.

 NIH/National Institute of Mental Health. "Scientists unveil complete cell map of a whole mammalian brain." ScienceDaily. ScienceDaily, 13 December 2023. www.sciencedaily.com/releases/2023/12/231213112909.htm>.