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Archive for the ‘Pharmaceutical Drug Discovery’ Category

China is Making Large Inroads into Biotech: Is Investment Money Following? Is US Investment Money Following the China Biotech Boom?

Curator: Stephen J. Williams, Ph.D.

 

A common route for raising capital or exit strategy for many US biotechs has been strategic transfer or sale of intellectual property (IP) or strategic partnership with large pharmaceutical companies looking to acquire new biotechnologies or expand their own pipelines. Most US based biotechs had enjoyed a favorable (although not fully exclusive) deal-making environment with US pharmaceutical companies with some competition from international biotech companies.  US government agencies such as FINRA, CFIUS, and the SEC closely monitored such international deals and the regulatory environment for such international deal making in the biotechnology space was tight.

 

Smaller Chinese biotechs have operated in the United States (at various biotech hubs around the country) and have usually set up as either service entities to the biotech industry as contract research organizations (Wuxi AppTech), developing research reagents for biotech (Sino Biological) or conducting research for purposes of transferring IP to a parent company in China.  Most likely Chinese biotechs set up research operations because of the overabundance of biotech hubs in the United States, with a dearth of these innovation hubs in the China mainland.

 

However, as highlighted in the Next in Health Podcast Series from PriceWaterHouseCoopers (PwC), China has been rapidly been developing innovation hubs as well as biotech hubs.  And Chinese biotech companies are staying home in mainly China and exporting their IP to major US pharmaceutical companies.  As PwC notes this deal making between Chinese biotech in China and US pharmaceutical companies have rapidly expanded recently.

 

The following are notes from PriceWaterHouseCoopers (PwC) podcast entitled: Strategic Shifts: Navigating China’s Biotech Boom and Its Impact on US Pharma:

 

You can hear this podcast on YouTube at https://music.youtube.com/podcast/iguywci6oG0 

 

Tune in as Glenn Hunzinger, PwC’s Health Industries Leader and Roel van den Akker, PwC’s Pharma and Life Sciences Deals Leader discuss the rapid rise of China’s biotech industry and what it means for U.S. pharmaceutical companies. They discuss the evolving role of Chinese biotech in the global innovation landscape and share perspectives on how U.S. pharmaceutical companies can thoughtfully assess opportunities, manage cross-border complexities, and build effective partnering and diligence strategies.

 

 Discussion highlights:

 

  • China’s biotech industry is growing fast and becoming a global player, with U.S. companies increasingly looking to partner with Chinese firms on cutting-edge science
  • U.S. pharma leaders are encouraged to move beyond skepticism and stay curious by building relationships, learning from local innovation, and exploring new partnership opportunities
  • Successfully partnering with Chinese biotech firms requires a careful and well-structured approach that accounts for global complexity, protects data and IP, and uses creative deal structures like new company formations to manage risk and stay flexible
  • U.S. companies need to be proactive in order to stay competitive by actively exploring global innovation, understanding the risks, and having a clear strategy to bring high-potential science to U.S. patients

 

Speakers:

 

Roel Van den Akker, Pharmaceutical and Life Sciences Deals Leader 

 

Glenn Hunzinger, Partner, Health Industries Leader, PwC

 

Linked materials:

 

https://www.pwc.com/us/en/industries/health-industries/health-research-institute/next-in-health-podcast/strategic-shifts-navigating-chinas-biotech-boom-and-its-impact-on-us-pharma.html 

 

China’s rise as a biotech innovation hub: 4 key strategic questions for US biopharma executives 

 

For more information, please visit us at: https://www.pwc.com/us/en/industries/..

 

In 2019 there were zero in licensing deals from China to US pharma…. Today one in five come from China.  

  1. China evolved into a expanding economy because China invested in biotech companies
  2. Lots of skilled people
  3. Built centers that rivaled biotech innovation centers in places like  Boston, California Bay  Area, and Philadelphia

China has gone from low cost manufacturing country to an innovative economy with great science coming out of it. US pharma boardrooms need to understand this

 

The analysts at PWC suggest to look at Data integrity, IP protection and risks before bringing China biotech IP  in US.  It is imperative that companies do ample due  diligence.

 

China’s rise as a biotech innovation hub: 4 key strategic questions for US biopharma executives

May 08, 2025

Roel van den Akker; Partner, Pharmaceutical & Life Science Deals Leader, PwC

China’s biotech sector is evolving at breakneck speed — and the implications for US pharma are too significant to ignore. Over the past five years, China has transitioned from being a nice to watch market to a central pillar of global biopharma innovation. Today, one-third of in-licensed molecules at US pharma multinationals originate from China, up from virtually zero in 2019.

China’s biotech sector, however, is not monolithic or uniform. The ecosystem spans high-quality, globally competitive biotech hubs in cities like Hangzhou and Suzhou — home to companies producing first-in-class and novel innovations in ophthalmology, cardiovascular, and immunology — as well as a long tail of undercapitalized players where execution and capability gaps remain profound.

And now, Washington is paying attention, too. A recent report from the US National Security Commission on Emerging Biotechnology (NSCEB) highlighted China’s ambitions to dominate biotech as a “strategic priority” with dual-use implications across health and security. The report urges the US government and private sector to reassess dependencies and increase scrutiny of biotechnology partnerships abroad. For the US biopharma industry, this isn’t just a supply chain concern — it is a boardroom issue.

With the licensing market still skewed toward buyers, venture funding remaining depressed in China and IPO windows in Hong Kong slowly reopening, there is a compelling window for US companies to secure differentiated assets at relatively attractive terms. Speedy deal execution is increasingly important as the highest quality assets are being quickly scooped up. But navigating this terrain can require more than opportunism. It calls for deliberate strategy, structured governance and a nuanced geopolitical risk framework.

Here are four questions every US biopharma executive should be asking:

1. What is our posture toward preclinical and clinical science from China?

Are we approaching Chinese innovation with a default posture of skepticism or strategic curiosity? Many top-tier Chinese biotechs are now generating US-caliber data at the speed of light, particularly in therapeutic modalities such as mAbs, ADCs and T-cell engagers, but plenty still have execution gaps. Those that elect to lean in will likely need a deliberate eco-system approach geared towards being the partner of choice and local brand building.

2. What does our China diligence playbook look like?

In light of national security concerns, companies need a China-specific diligence framework — one that goes beyond the science. This includes scrutiny around data integrity, IP protection, export controls, and cross border data sharing.

3. What is our plan post-licensing or acquisition?

Ownership is just the start. US companies need a clear strategy for globalizing China-origin assets — from IND transfers to FDA filing to commercial launch. In some cases, that may require reworking the preclinical package or rebuilding the CMC infrastructure entirely. Increasingly, US (or Europe)-based “Newcos” may serve as geopolitical firewalls.

4. How can we preserve agility amid regulatory and political volatility?

With rising US-China tensions and new export control proposals under review, companies must future-proof deal structures. This could include regional carveouts, US-only development rights, or milestone-gated commitments. The NSCEB report makes clear: passive engagement is no longer tenable.

Innovation strategy meets national interest

The trendlines are clear: China is not just a manufacturing hub — it is an increasingly important source of global biotech innovation. But sourcing innovation from China now sits at the intersection of science, strategy and security. US pharma and biopharma companies can no longer afford to treat China engagement as tactical. Those who adopt a deliberate, resilient and agile China strategy — grounded in scientific rigor and geopolitical realism — likely lead in tomorrow’s innovation race.

 

Source: https://www.pwc.com/us/en/industries/health-industries/library/china-biotech-sector.html 

 

US pharma bets big on China to snap up potential blockbuster drugs

By Sriparna Roy and Sneha S K

June 16, 202511:26 AM EDTUpdated June 16, 2025

A researcher prepares medicine at a laboratory in Nanjing University in Nanjing, Jiangsu province, April 29, 2011. REUTERS/Aly Song/File Photo Purchase Licensing Rights

, opens new tab

  • U.S. drugmakers turn to Chinese companies as they face patent expirations
  • Licensing deals accelerate while traditional mergers decline
  • Chinese biotechs are challenging Western peers, analysts say

June 16 (Reuters) – U.S. drugmakers are licensing molecules from China for potential new medicines at an accelerating pace, according to new data, betting they can turn upfront payments of as little as $80 million into multibillion-dollar treatments.

Through June, U.S. drugmakers have signed 14 deals potentially worth $18.3 billion to license drugs from China-based companies. That compares with just two such deals in the year-earlier period, according to data from GlobalData provided exclusively to Reuters.

 

How to stop the shift of drug discovery from the U.S. to China. The FDA must make it easier to do such work in the U.S.

Scott GottliebMay 6, 2025

 

Five years ago, U.S. pharmaceutical companies didn’t license any new drugs from China. By 2024, one-third of their new compounds were coming from Chinese biotechnology firms.

Why are U.S. drugmakers sending their business to China? As in many other industries, it’s so much cheaper to synthesize new compounds inside Chinese biotechnology firms once a novel biological target has been discovered in American laboratories.

Yet the costs of developing new drugs in the U.S. needn’t be so high. They are driven up, in part, by increasing regulatory requirements that burden early-stage drug discovery in America. That’s especially true for Phase I clinical trials, in which drugs are tested in people for the first time.

Newsletter

The smartest thinkers in life sciences on what’s happening — and what’s to come

This shift of discovery work to China is going to accelerate if we don’t take deliberate steps to make it easier to do such work here in America. Yet the imperative to modernize early-stage drug development — to ensure that groundbreaking drug discovery remains in the U.S. rather than migrating to China — is colliding head-on with an impulse to slash the very government workforce capable of spearheading these reforms. These conflicting impulses have created a paradoxical tension: on one hand, the desire to stay competitive with China in biotechnology innovation, and on the other, a parallel campaign to reduce and in some cases dismantle the investments and institutions essential to achieving that goal.

In most cases, Chinese firms are not discovering new biological targets, nor are they crafting genuinely novel compounds to engage these targets through homegrown Chinese research. Instead, they piggyback on Western innovations by scouring U.S. patents, zeroing in on biological targets that are initially uncovered in American labs, and then developing “me too” drugs that replicate American-made compounds with only superficial tweaks, or producing “fast follower” drugs that capitalize on the original breakthroughs while refining key features to try to surpass U.S. innovation. Facing fewer regulations, the Chinese drugmakers can move more quickly than U.S. biotechnology companies — synthesizing copy-cat drugs based on our biological advances and then promptly moving these Chinese-made compounds into early-stage clinical trials, outpacing their American counterparts.

According to the investment bank Jefferies, large American drug companies spent more than $4.2 billion over the past year licensing or acquiring new compounds originally synthesized by Chinese firms. Many comprised advanced compounds such as antibody drugs and cell therapies — underscoring Chinese companies’ growing sophistication in adopting the latest American technologies. The cost of licensing these compounds from China, rather than synthesizing them in American labs, can be significantly lower. At a time when research funding in the U.S. is being cut, and research budgets are becoming painfully stretched, companies are looking to lower the cost of building their pipelines. In a fast-moving field such as oncology, this shift toward Chinese-synthesized compounds is particularly striking: I am told by someone inside the FDA process that nearly three-quarters of new small molecule cancer drugs submitted to the Food and Drug Administration for permission to begin U.S.-based clinical trials are initially made in China.

Usually, only a few months elapse between the moment a U.S. research team publishes a patent identifying a new biological target and when a biotechnology firm in China creates the corresponding drug that capitalizes on these findings. Because Chinese firms can synthesize new molecules at a fraction of the cost incurred by U.S. biotechnology companies — owing to a large and skilled but much cheaper workforce — they find the most intriguing biological targets pursued by Western researchers, rapidly churning out potent yet less expensive copycat molecules that they then market to Western companies.

A major challenge for U.S. firms is the long and costly process of obtaining FDA approval for Phase I studies, in which drugmakers test a new drug’s safety and tolerability in a small group of human volunteers. In China, launching this initial phase of clinical trials is far simpler, giving Chinese biotechnology companies a competitive advantage: By swiftly advancing their molecules into early-stage patient testing, Chinese firms can more readily determine which compounds hit their biological targets and show the greatest therapeutic promise. This allows the Chinese firms to quickly refine their molecules and then leapfrog their American counterparts, who are slowed by more cautious regulatory processes. While China’s regulatory process doesn’t uphold the patient safeguards that Americans rightly insist upon, the U.S. FDA could still streamline its path into early-stage drug development, bolstering America’s competitive edge without compromising patient safety.

In the U.S., one of the costliest early hurdles is the exhaustive animal testing that the FDA requires before a drug can be advanced into Phase I studies. These “pre-clinical” studies help safeguard patients, but the agency also uses this testing to weed out potential failures before a drug requires more intensive FDA scrutiny in later trials.

Over time, this regulatory framework has frontloaded a significant share of costs to the earliest phases of drug development, when biotechnology startups are often running on shoestring budgets, lack clinical data to attract investors, and can least afford delays. One measure of the increasing difficulty in securing the FDA’s permission for Phase I trials is the growing number of U.S. drugmakers who take compounds discovered on American soil and conduct these clinical trials in other Western markets, where they can obtain data more quickly and inexpensively before bringing it back to the FDA. One popular locale is Australia, where costs run about 60% lower than U.S.-based clinical trials, largely because the Australian government offers tax incentives to attract this kind of biomedical investment.

Many animal studies address esoteric questions about a drug’s long-term effects on parameters that may not be relevant to its eventual use — for example, at doses and durations of use that may be far beyond how patients will ultimately use the drug. The FDA’s preclinical testing protocols sometimes require American researchers to administer new compounds to animals at levels up to 500 times higher than any intended dose for patients, aiming for maximum animal exposure before human trials can begin. Where the FDA needs to screen for certain remote risks, many animal studies could be safely deferred until human trials confirm that a drug may benefit patients. At that point, it becomes easier for biotechnology companies to raise capital to fund these pro forma testing efforts.

To modernize the process, the FDA could tap into the wealth of data from existing drugs to establish a more phased approach to these requirements, where the amount of initial animal testing is more closely matched to a drug’s novelty and a better estimation of its perceived risks. It’s a prime opportunity to employ artificial intelligence — mining current data and extrapolating known information to newly discovered molecules. For new molecules that share structural similarities with established drugs, where a robust body of safety information already exists (and the likelihood of uncovering novel risks is judged to be minimal), some animal studies might simply be unnecessary. To establish a graduated approach to the scope of pre-clinical toxicology studies that the FDA requires for new molecules, Congress could revise the agency’s statutory framework, explicitly empowering it to adopt such flexible standards. It would also require targeted investments, enabling the FDA to craft the necessary tools and protocols to implement these refined methodologies.

Mice and even primates are often poor proxies for many of the remote toxicities the FDA is trying to test for, anyway. The agency can also make a more concerted effort to adopt advanced technologies, like pieces of human organs embedded in chips that can be used to test for remote dangers a drug may pose to specific organs like the heart and liver. These tools can reliably screen for risks at a fraction of the time and cost. FDA Commissioner Marty Makary recently announced his intention to pursue a plan that would phase out animal studies in the preclinical evaluation of antibody drugs, shifting instead toward innovative technologies that assess toxicology without relying on live animals. This positive step requires the FDA to invest in new capabilities, and scientific staff that possess expertise in these novel domains.

But right now, that investment seems unlikely. The size and scientific scope of the FDA staff responsible for reviewing early-stage drug development — and evaluating data collected from animal studies — has failed to keep up with the increasing complexity and sheer volume of applications flooding into the agency to launch Phase I clinical trials. Now, the FDA has made deep staffing cuts, prompted by DOGE, that have specifically targeted scientific teams that would lead these essential reforms.

Adding to these woes, morale at the FDA has declined so markedly that many foresee a wave of voluntary resignations among clinical reviewers. By thinning the ranks of experts who tackle novel scientific questions and resolve issues that span across different drug development programs — especially the elimination of the policy office within the FDA’s Office of New Drugs, which adjudicated these kinds of cross-cutting scientific questions — the government has impeded the early dialogue with drug developers that often results in streamlining requirements for Phase I studies. Even more challenging, it weakens the staff’s ability to develop new guidance documents and put better review practices into place — reforms essential for lasting improvements to the preclinical review process.

Instead of strengthening America’s biotechnology ecosystem, such measures risk accelerating the migration of discovery activities to China, undermining innovation at home. When U.S. drugmakers license compounds from China, they divert funds that might otherwise bolster innovation hubs such as Boston’s Kendall Square or North Carolina’s Research Triangle. The U.S. biotechnology industry was the world’s envy, but if we’re not careful, every drug could be made in China.

Scott Gottlieb, M.D., is a senior fellow at the American Enterprise Institute and served as commissioner of the Food and Drug Administration from 2017 to 2019. He is a partner at the venture capital firm New Enterprise Associates and serves on the boards of directors of Pfizer Inc. and Illumina.

From FierceBiotech: US Biotech Companies are finding that foreign investments may put them in a precarious position for government funding

Source: https://www.fiercebiotech.com/biotech/us-appears-be-terminating-grants-biotechs-investors-certain-countries 

 

By Gabrielle Masson  Jun 18, 2025 11:50am

 

By Gabrielle Masson  Jun 18, 2025

The Department of Health and Human Services is allegedly denying clinical trial funding for biotechs based on their ties to certain foreign investors, Fierce Biotech has learned.

At the BIO conference in Boston this week, Fierce spoke with a biotech executive who had their grant pulled, as well as an industry thought leader who backed up the claims about a change in the HHS’ funding approach.

“We’re in a situation where some of the companies are confused about their ability to take foreign investment,” said John Stanford, founder and executive director of Incubate, a nonprofit organization of biotech venture capital firms and patient advocacy groups designed to educate policymakers on life science investment and innovation.

“We’ve been hearing about SBIR grants canceled,” Stanford told Fierce in a separate interview at BIO. “Anecdotally, we’ve also heard it’s a lot more than China and it’s countries—Canada, Norway, the EU—that traditionally we think of as allies.”

“Again, that’s anecdotal,” he stressed. “But we would be very concerned [about] the idea that we won’t take Canadian investments or Japanese investments or EU-based investments.”

“We want foreign investors coming to U.S.-based companies to develop drugs for the world,” Stanford said. “That is a win-win-win.”

Back in February, President Donald Trump issued a memorandum titled the “America First Investment Policy” that aims to restrict both inbound and outbound investments related to “foreign adversaries” in certain strategic industries. The document lacks specifics but puts China front and center while mentioning both healthcare and biotech among the sectors it will regulate.

And the investment analysis firm Jeffries noted that

 

Looking at financial data from FactSet, Jefferies analysts found biotech funding in May 2025 was down 57%, to just over $2.7 billion, compared to the same time last year. That sum was only slightly better than the nearly $2.6 billion raised in April — the worst haul in three years — and was also 44% lower than the average seen across the past 12 months.

 

Source: https://www.biopharmadive.com/news/biotech-funding-trump-policy-ipo-venture-pipe/749784/ 

 

But according to other Jeffries analysis biotech investment is not diminishing but realigning and maybe going international:

 

From Health Tech World: https://www.htworld.co.uk/insight/opinion/biotech-investment-isnt-shrinking-its-smarter-fn25/ 

Today, total capital remains relatively steady, but it’s flowing differently.

Fewer companies are commanding a greater share of investment, and a new global map of biotech leadership is emerging—one where Israel, Italy, Korea, Saudi Arabia, and NAME are not just participants but strategic innovators and investors in the space.

While some correction was inevitable after the pandemic’s urgency subsided, the sector’s foundation had already changed.

CROs didn’t scale down; they doubled down, offering sponsors the flexibility to develop therapies without taking on the full weight of manufacturing and trials in-house.

This shift underpinned a new era of capital efficiency and strategic outsourcing, which is strongly influenced by new smart technologies that generate code and content at a blink of an eye and refine research protocols.

Selective but Strong: The New Capital Math

After the surge of 2020–2021, a funding correction began in late 2022.

According to Jefferies, biotech funding in May 2025 was down 57 per cent year-over-year, dropping to roughly $2.7 billion.

Public markets also cooled. In 2023, biotech IPOs hit their lowest numbers in a decade, and follow-on offerings became increasingly rare.

This deceleration prompted talk of a “biotech winter.” Yet key indicators suggest a market in transition rather than decline. Private equity and venture capital remain active but are more selective.

While early-stage companies face greater hurdles, late-stage biotechs and those with de-risked clinical programs continue to attract significant funding.

Follow the Late-Stage Money

A recent GlobalData report underscores this trend: late-stage biotech companies now receive nearly double the capital of their earlier-stage counterparts.

Median venture rounds for Phase III companies have climbed to $62.5 million, as investors increasingly prioritise assets with regulatory clarity and near-term commercialisation potential.

The post-COVID period has revealed an important funding shift: fewer biotech companies are securing a larger percentage of available capital.

In an environment of macroeconomic uncertainty, geopolitical risk, and rising interest rates, investors are retreating from speculative bets and doubling down on known quantities.

From Gemini: Is US biotech investment going overseas in 2025? Plot in a bar graph the US biotech investment versus worldwide biotech investment by country

Is US biotech investment going overseas in 2025? Plot in a bar graph the US biotech investment versus worldwide biotech investment by country

Yes the US has many more venture capital  firms focused on Biotech investment but it is appearing that investment is not staying in the US.

The global biotech funding landscape in 2023: U.S. leads while Europe and China make strides

Earth planet inside DNA molecule. Elements of this image are furnished by NASA

[Image courtesy of Sergey Nivens/Adobe Stock]

In 2023, the U.S. continued to demonstrate its position as the biotech funding leader, commanding over one-third, 35%, of the global investment in the sector. Overall, U.S. biotech firms attracted $56.79 billion in funding, according to a survey of Crunchbase data. Next in line was China, which contributed about 12.7% to the global funding pool, or $20.61 billion. Up next was Europe, which secured more than $11.46 billion and representing more than 7% of the worldwide funding. 

While U.S. leads in total biotech funding, Chinese biotech companies, on average, saw larger funding rounds than either Europe or the U.S. The average funding size per company in China was roughly three times larger than that in the U.S. and six times larger than the average in Europe.

But while China-based companies had larger hauls, they were comparatively few. Chinese biotech secured in cumulative $20.61 billion among just 69 firms, with roughly $299 million in funding per company on average. Meanwhile, the 229 European biotech firms that won funding in the past year attracted $11.46 billion in funding, averaging $50 million each. In comparison, the 583 U.S. biotech companies with recent funding attracted $56.79 billion, averaging $97 million per company.

The map below represents the total biotech funding amount in USD across the globe. Funding amounts are shaded based on companies’ cumulative funding totals and density. Darker shades indicate higher funding amounts and density, with the U.S. hubs on the East and West Coasts showing the darkest shade, reflecting the combination of total funding and density.

The Chinese Biotech Market is expected to grow to over 800 million in 2025. This is on the heels of phenomenal growth from 2013, where almost a ten fold increase in market size growth has been seen from 2013 to 2025. Source: https://www.franklintempleton.co.uk/articles/2025/clearbridge-investments/china-emerging-as-a-global-biotechnology-player

 

Size of the US Biotech Market is expected to grow from half a billion in 2023 to 1.7 trillion in 2033. Source novaoneadvisor.com

 

Biotech investment trends in the US for 2025 present a complex picture. While some reports indicate a general slowdown in venture funding for biotech startups and concerns about tariff impacts, other sources suggest resilience within the sector, with strong revenue growth for public biotech companies in both the US and Europe in 2024, expected to continue into 2025. Additionally, there are calls for significant investment within the US to maintain its leadership in biotechnology. Therefore, it is not definitively clear that US biotech investment is predominantly going overseas in 2025, but rather navigating a challenging and evolving landscape.

Regarding US biotech investment versus worldwide biotech investment by country, here is a bar graph of key biotech investment moves in 2025 based on available data. Please note that this data reflects “key moves” in biotech funding for 2025 as reported by Labiotech, and a comprehensive worldwide investment breakdown for all countries was not available.

From Franklin Templeton: China is Emerging as a Global Biotechnology Player

See Source for more: https://www.franklintempleton.co.uk/articles/2025/clearbridge-investments/china-emerging-as-a-global-biotechnology-player 

The combined value of China’s outside licensing deals reached around US$46 billion in 2024, up from US$38 billion in 2023 and US$28 billion in 2022, according to data provider NextPharma. Meanwhile, the number of global companies licensing into China has decreased across the same period. These tailwinds have helped China expand its share of global drug development to nearly 30% compared to 48% for the United States, according to data provider Citeline. Strong IP protection has positioned China to receive global investment, with a 2024 policy encouraging more IP collaboration between global and Chinese companies. US investment bank Stifel projects that molecules licensed by large pharmaceutical firms from China will increase to 37% in 2025. This shift has been largely driven by US companies seeking cheaper drug development alternatives and has led to R&D spending in China outpacing that of the United States.

A Closer Look at the Financials and Comparison between China and US Biotech Investment Trends

This rapid growth of Chinese biopharma was predictable back in 2018 as this article from an investment newsletter suggests:

China’s Biopharma Industry: Market Prospects, Investment Paths

Source: https://www.china-briefing.com/news/china-booming-biopharmaceuticals-market-innovation-investment-opportunities/ 

November 10, 2022Posted by China BriefingWritten by Yi WuReading Time:  5 minutes

Biopharma, short for biopharmaceuticals, are medical products produced using biotechnology (or biotech). Typical biopharma products include pharmaceuticals generated from living organisms, vaccines, gene therapy, etc.

An important subsector of biotech, China’s biopharma industry has much attention home and abroad, especially after Chinese companies developed multiple COVID-19 vaccines now in wide circulation. Market capitalization of Chinese biopharma companies grew to over US$200 billion in 2020 from US$1 billion in 2016.

With China’s rapidly aging population and a growing affluent middle-class, the country’s biopharma industry presents challenging but compelling opportunities to investors.

In this article, we discuss the market size, growth drivers, and global competition facing China’s biopharma industry and suggest potential investment paths.

How big is China’s biopharma market?

Biopharmaceuticals in China is a lucrative business, with significant domestic demand due to an aging population and expanding household budgets for quality products and services as people’s living standards improve.

China’s healthcare market is predicted to expand from around US$900 billion (RMB 6.47 trillion) in 2019 to US$2.3 trillion (RMB 16.53 trillion) in 2030, and its market size is second to only the US. China’s total expenditure on healthcare as a component of its GDP increased to 5.35 percent in 2019 from 4.23 percent in 2010.

Specifically to the biopharma industry, the market size will likely grow from RMB 345.7 billion (US$47.60 billion) in 2020 to RMB 811.6 billion (US$111.76 billion) in 2025, an 135 percent increase in five years. Similarly, market capitalization of Chinese biopharma companies grew from US$1 billion in 2016 to over US$200 billion in 2020. From 2010 to 2020, 141 new drug and biotech companies were launched in China, doubling from the previous decade.

What are the growth drivers for China’s biopharma industry?

The broader biotech sector is a main focus of the Chinese government’s “Made in China 2025” strategy. The country needs a steady biopharmaceutical industry to address its healthcare needs and to build an internationally competitive and innovative pharmaceutical industry as part of wider economic restructuring. Under the same momentum, on January 30, 2022, nine agencies jointly issued the “14th Five-year Plan for the Development of the Pharmaceuticals Industry” as a guiding document that clarifies the goals and directions for China’s pharmaceutical industry development in the next five years.

Now let’s compare the size of the US biotech market: You can see the US biotech valuation is now similar to the estimated market capitalization of the China market.

 

The U.S. biotechnology market size was valued at USD 621.55 billion in 2024 and is projected to reach USD 1,794.11 billion by 2033, registering a CAGR of 12.5% from 2024 to 2033. Ongoing government initiatives are the key factors driving the growth of the market. Also, improving approval processes coupled with the favorable reimbursement policies can fuel market growth further.

Key Takeaways:

  •         DNA sequencing dominated this market and held the highest revenue market share of 18% in 2023
  •         The others’ segment is anticipated to grow at the fastest CAGR of 28.1% during the forecast period.
  •         The health segment dominated the market and accounted for the largest revenue market share of 44.13% in 2023.
  •         Bioinformatics is expected to witness the fastest growth, with a CAGR of 17.2% during the forecast period.

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The U.S. biotechnology market is witnessing major growth contributed by the increasing adoption and applications of biotechnology in many industries like pharmaceuticals, agriculture, food production, environmental conservation, and energy. In addition, market players in the industry are increasingly focusing on innovations across many fields such as energy, medicine, and materials science using biological processes to overcome challenges and fuel technological advancements. Also, in recent years there has been a notable surge in the utilization of biotechnological methods including DNA fingerprinting, stem cell technology, and genetic engineering propelling the market expansion soon.

 

From BioPharmaDive

Source: https://www.biopharmadive.com/news/biotech-us-china-competition-drug-deals/737543/ 

‘The bar has risen’: China’s biotech gains push US companies to adapt

A fast-improving pipeline of drugs invented in China is attracting pharma dealmakers, putting pressure on U.S. biotechs and the VC firms that back them.

Published Jan. 16, 2025

Ben Fidler

Senior Editor

Soon after starting a new biotechnology company, David Li realized he needed to rethink his strategy. 

Li had been conducting the competitive research biotech entrepreneurs typically undertake before soliciting investment. He drew up a list of drug targets that his startup, Meliora Therapeutics, could pursue and checked them against the potential competition. 

Li quickly found that biotechs in China were already working on many of the targets he had on his list. Curious, he visited Shanghai and Suzhou and witnessed a buzzing scene of startups set frenetically to task. 

The latest developments in oncology research

“They’re not really thinking about the U.S. at all. They’re just trying to create more value and stay alive to differentiate themselves from the next guy in China,” he said. “They’re moving quick. There are a lot of them and they’re just quite competitive.”

Li’s experience is illustrative of a trend that could pressure biotech companies in the U.S. and alter their drug development strategies. More and more, large pharmaceutical companies are licensing experimental drugs from China. Venture companies are testing similar tactics by launching new U.S. startups around compounds sourced from China’s laboratories. This shift has been sudden, with licensing deals ramping rapidly over the past two years. And it is occurring even as the shadow of U.S.-China competition within biotech grows longer. 

Executives and investors interviewed by BioPharma Dive at the J.P. Morgan Healthcare Conference this week share Li’s outlook. They expect such deals will accelerate and, in the process, force U.S. biotechs to work harder to stand out. 

“We’ve been warning people for a while, we’re losing our edge,” said Paul Hastings, CEO of cell therapy maker Nkarta and former chair of the U.S. lobbying group the Biotechnology Innovation Organization. “Innovation is now showing up on our doorstep.”

There’s perhaps no clearer example of this than ivonescimab, a drug developed by China-based Akeso Therapeutics and licensed by U.S.-based Summit Therapeutics. Recent results from a lung cancer study run in China showed ivonescimab outperformed Keytruda, Merck’s dominant immunotherapy and currently the pharmaceutical industry’s most lucrative single product. 

The finding “put a huge focus on what’s happening in China,” said Boris Zaïtra, head of business development at Roche, which sells a rival to Keytruda. 

Fast-moving research

Today’s deal boom has roots in efforts by the Chinese government to upgrade the country’s biotech capabilities by upping investment in technological innovation. In the life sciences, the initiative provided funding, discounted or even free laboratory space and grants to support what Li described as a “robust ecosystem” of biotechs. 

The results are clear. Places like Shanghai and Suzhou are home to a skilled workforce of scientists and hundreds of homegrown companies that employ them. Science parks akin to the U.S. biotech hubs of Cambridge, Massachusetts and San Francisco have sprouted up. 

Chinese companies generally can move faster, and at a lower cost, than their U.S. counterparts. Startups can go from launch to clinical trials in 18 months or less, compared to a few years in the U.S., Li estimated. Clinical trial enrollment is speedy, while staffing and supply chain costs are lower, helping companies move drugs along more cost effectively. 

“If you’re a national company within China running a trial, just by virtue of the networks that you work within, you pay a fraction of what we pay, and the access to patients is enough that you can go really fast,” said Andy Plump, head of research at Takeda Pharmaceutical. “All of those are enablers.” 

And what they’ve enabled is a large and growing stockpile of drug prospects, many of which are designed as “me too better” versions of existing medicines, analysts at the investment bank Jefferies wrote in a December report. Initially focused in oncology, China-based companies are now churning out high-quality compounds across multiple therapeutic areas, including autoimmune conditions and obesity

“There was a huge boom of investment in China, cost of capital was very low, and all these companies blew out huge pipelines,” said Alexis Borisy, a biotech investor and founder of venture capital firm Curie.Bio. ”Anything that anybody was doing in the biotech and pharmaceutical industry, you could probably find 10 to 50 versions of it across the China ecosystem.”

Me-toos become me-betters

For years now, Western biopharma executives have scouted the pipelines of China’s biotech laboratories — exploration that yielded a smattering of licensing deals and research collaborations. Borisy was among them, starting in 2020 a company called EQRx that sought to bring Chinese versions of already-approved drugs to the U.S. and sell them for less. EQRx’s plan backfired amid scrutiny by the U.S. Food and Drug Administration of medicines tested only in people from a single country.

Now, however, the pace of deals has accelerated rapidly. There are a few reasons for this. According to Plump, one is the improving quality of the drug compounds being developed. The “me toos” are becoming “me betters” that could surpass available therapies and earn significant revenue for companies — like BeiGene’s blood cancer drug Brukinsa, which, in new prescriptions for the treatment of leukemia, overtook two established medicines of the same type last year. 

Another reason, Plump said, is that China-based companies are becoming more innovative, studying drug targets that might not have yet yielded marketed medicines, or for which the most advanced competition is in early testing. Li notes how Chinese companies are going after harder “engineering problems,” like making complex, multifunctional antibody drugs, or antibody-drug conjugates. 

“There are so many [companies] that the new assets are going to keep coming,” Li said. 

Inside the market strategies of today’s drugmakers

Much as in the U.S., China-based biotechs are also fighting for funding, pushing them to consider licensing deals with multinational pharma companies. At the same time, these pharmas are hunting for cheap medicines they can plug into their pipelines ahead of looming patent cliffs. The two trends are “colliding,” said Kristina Burow, a managing director with Arch Venture Partners. “I don’t see an end to that.”

The statistics bear Burow’s view out. According to Jefferies, the number and average value of deals for China-developed drugs reached record levels last year. Another report, from Stifel’s Tim Opler, showed that pharma companies now source about one-third of their in-licensed molecules from China, up from around 10% to 12% between 2020 and 2022. 

“I see huge opportunities for us to partner and work together with Chinese companies,” said Plump, of Takeda. 

Several venture-backed startups have been built around China-originated drugs, too, among them Kailera Therapeutics, Verdiva Bio, Candid Therapeutics and Ouro Medicines, all of which launched with nine-figure funding rounds. 

“There’s been a lot of really good, high quality molecules and data that have emerged from China over the last couple of years,” said Robert Plenge, the head of research at Bristol Myers Squibb. “It’s also no longer just simply repeating what’s been done with the exact same type of molecule.”

Geopolitical risks

These deals are happening against an uncertain backdrop. The U.S. Congress has spent the last year or so kicking around iterations of the Biosecure Act, a bill that would restrict U.S. biotechs from working with certain China-based drug contractors. A committee in the House of Representatives is calling for new limits on clinical trials that involve Chinese military hospitals. And the incoming Trump administration has threatened tariffs that could ripple across industrial sectors. 

“We don’t know what this new administration is going to do,” said Jon Norris, a managing director at HSBC Innovation Banking.

The Biosecure Act “keeps going sideways,” added Hastings, who believes that any impact from the legislation, if passed, would be minimal. Instead, Hastings wonders if future tariffs may be more problematic. “There will be tariffs on other goods coming from China. Does that include raw materials and innovation? It’s hard to imagine that it won’t,” he said. 

But executives and investors expect deals to continue, meaning U.S. biotechs will have to do more to compete. 

“U.S. companies will need to figure out what it is they’re able to bring to the table that others can’t,” said Burow, of Arch. 

Borisy said startups working on first-of-their-kind drugs need to be more secretive than ever. “Do not publish. Do not present at a scientific meeting. Do not put out a poster. Try to make your initial patent filing as obtuse as possible,” he cautioned. 

“The second that paper comes out, or poster at any scientific meeting, or talk or patent, assume it has launched a thousand ships.”

Those that are further along should assume companies in China will be quick on their heels with potentially superior drugs. “The day when you could come out with a bad molecule and open up a field is over,” he said. 

Greater competition isn’t necessarily a bad thing, according to Neil Kumar, CEO of BridgeBio Pharma. Drug development could become more efficient as pharmas acquire medicines from a “cheaper” starting point and advance them more quickly. 

Venture dollars could be directed towards newer ideas, rather than standing up a host of similar companies.“If all of a sudden this makes us less ‘lemming-like,’” Kumar said, “I have no problem with that.”

Li similarly argues that, going forward, U.S. companies need to focus on “novelty and innovation.” At his own company, Li is now working on things “we felt others were not able to access.”

“The game has always been the same. Bring something super differentiated to market,” he said. But “the bar has risen.” 

 Gwendolyn Wu and Jacob Bell contributed reporting. 

Is Chinese Biotechs just Producing Me-Too Drugs or are they Innovating New Molecular Entities?

The following articles explain the areas in which Chinese Biotech is expanding and focused on.

However the sort answer and summary to the aforementioned question is: Definately Chinese Biotechs are innovating at a rapid pace, and new molecular entities and new classes of drugs are outpacing any copycat or mee-too generic drug development.

This article  by Joe Renny on LinkedIn focuses on the degree of innovation in Chinese biotech companies. I put the article in mostly its entirety because Joe did an excellent analysis of China’s biotech industry.

You can see the full article here: https://www.linkedin.com/pulse/copy-chinas-biotech-boom-can-really-solve-pharmas-roi-joe-renny-rerge/ 

China’s Biotech Boom: Can It Really Solve Pharma’s ROI Problem?

Joe Renny

Joe Renny: Strategic Growth Leader | Driving M&A, Pharma Partnerships & Innovation | Unlocking the Commercial Potential of Science | Biotech & Pharmaceuticals

China’s biotech sector is in the midst of a stunning surge – its stocks have skyrocketed over 60% this year (outpacing even China’s high-flying tech sector), and the country now has over 1,250 innovative drugs in development, nearly catching up with the U.S. pipeline of ~1,440. Once known mainly for generic manufacturing, China is rapidly emerging as a source of differentiated innovation. Global pharma giants have taken notice: major licensing deals are proliferating as Western drugmakers snap up Chinese-born therapies in fields like oncology, metabolic diseases (obesity/diabetes), and immunology. The excitement is palpable – but a critical question looms beneath the optimism: Can this wave of innovation meaningfully improve the pharmaceutical industry’s return on investment (ROI)? In other words, will China’s biotech boom fix the underlying economics of drug development, or are the same old ROI challenges here to stay?

From Copycats to Cutting-Edge: China’s Rapid Ascent in Biotech

In the past decade, China’s pharma landscape has transformed from copycat chemistry to cutting-edge biotech. The sheer scale of innovation is unprecedented. A recent analysis found China had over 1,250 novel drug candidates enter development in 2024, far surpassing the EU and nearly reaching U.S. levels. This is a remarkable jump from just a few years ago – back in 2015, China contributed only ~160 compounds globally. Reforms to streamline drug approvals and massive R&D investments (spurred by initiatives like Made in China 2025) have unleashed a boom led by returnee scientists and ambitious startups.

Importantly, the quality of Chinese innovation has leapt upward alongside quantity. Drugs originating in China are increasingly clearing high bars of efficacy and safety. The world’s strictest regulators, including the U.S. FDA and European EMA, have begun fast-tracking more Chinese-developed drugs with priority reviews and “breakthrough” designations. For example, a cell therapy for blood cancer developed by China’s Legend Biotech won FDA approval (marketed by Johnson & Johnson) and is considered superior to a rival U.S. therapy. Another China-origin drug – Akeso Inc.’s novel cancer antibody that outperformed Merck’s Keytruda in trials – triggered a global wave of interest and a $500 million licensing deal in 2022. In short, China is no longer just a low-cost manufacturing base; it’s producing world-class treatments that Big Pharma is eager to get its hands on.

This trend is also evident in the stock markets. After a four-year slump, Chinese biotech stocks have roared back, becoming one of Asia’s best-performing sectors in 2025. The Hang Seng Biotech Index in Hong Kong is up over 60% since January, vastly outperforming broader tech indices. Investors are excited by signals that China is becoming a true global hub for biopharma innovation. According to one analyst, “China biotech is now a disruptive force reshaping global drug innovation… The science is real, the economics are compelling, and the pipeline is starting to deliver”. All of this represents a fundamental shift in the industry’s centre of gravity – and perhaps a new source of competitive pressure on Western incumbents.

Western Pharma’s Response: Licensing Deals and Partnerships Accelerate

Global pharmaceutical companies aren’t standing on the sidelines – they’re rushing to collaborate with and invest in Chinese biotechs. In fact, U.S. and European drugmakers have dramatically stepped up licensing deals to tap China’s innovations. Through the first half of 2025 alone, U.S. companies signed 14 licensing agreements worth up to $18.3 billion for Chinese-origin drugs, a huge jump from just 2 such deals in the same period a year earlier. Many of these partnerships involve potential blockbusters in cancer, metabolic disorders, and other areas where Chinese R&D is making leaps.

  • Oncology: China has become a hotbed for cancer drug innovation, especially with advanced biologics like bispecific antibodies. In May 2025, Pfizer paid a record $1.25 billion upfront to license a PD-1/VEGF bispecific antibody from China’s 3SBio (a deal worth up to $6 billion with milestones). Weeks later, Bristol Myers Squibb struck an $11.5 billion alliance for a similar immunotherapy developed in China. Virtually every active clinical trial for certain cutting-edge cancer combos (like PD-1/VEGF drugs) now originates in China, making it a goldmine for Western firms seeking the next breakthrough. AstraZeneca, Merck, Novartis, and others have all scooped up Chinese cancer therapies in recent years as they cast their nets wider for innovation.
  • Metabolic & Obesity Drugs: Western pharma is also eyeing China’s contributions in metabolic diseases. Notably, Merck licensed a Chinese-developed GLP-1 oral drug (for diabetes/obesity) from Hansoh Pharma in late 2022 for up to $1.7 billion. And in 2025, Regeneron paid $80 million upfront (in a deal worth up to $2 billion) for rights to an experimental obesity drug from Hansoh. These deals underscore that Chinese labs are producing competitive candidates in the red-hot obesity/diabetes arena – an area of huge global market potential.
  • Autoimmune & Other Areas: While oncology leads, Chinese biotechs are also advancing novel therapies in immunology and autoimmune diseases. For example, multiple deals in 2024–25 have focused on inflammatory conditions and neurology, indicating breadth in China’s pipeline. As one industry banker observed, roughly one-third of all new assets licensed by large pharmas in 2024 originated from China, and this could rise to 40–50% in coming years. In other words, nearly half of Big Pharma’s in-licensed pipeline may soon be sourced from China – a radical change from a decade ago.

Underpinning this deal frenzy is a stark reversal of roles: China has shifted from mostly importing therapies to now exporting its homegrown innovations. Back in 2015, Chinese companies mainly signed “license-in” deals to bring foreign drugs to China. But by 2024, nearly half of China’s transactions were license-out deals, with Chinese firms granting global rights to their own drugs. In 2024 alone, Chinese biotechs out-licensed 94 novel projects to overseas partners, often at early clinical stages. This boom in outbound deals – especially for high-value cancer therapies (like ADCs and bispecific antibodies) – highlights China’s maturation as an innovation engine.

In a scientific paper published by Yan et al, the authors provided a comparative analysis between the US, EU, and China of new approved drugs from the years 2019- 2023.

Yan Y, Guo X, Li Z, Shi W, Long M, Yue X, Kong F, Zhao Z. New Drug Approvals in China: An International Comparative Analysis, 2019-2023. Drug Des Devel Ther. 2025 Apr 3;19:2629-2639. doi: 10.2147/DDDT.S514132.

In the paper, the authors retrieved approval data from from the National Medical Products Administration (NMPA), Food and Drug Administration (FDA), European Medicines Agency (EMA), and Pharmaceuticals and Medical Devices Agency (PMDA), including information on the generic name, trade name, applicants, target, approval date, drug type, approved indications, therapeutic area, the highest R&D status in China, and special approval status. The approval time gaps between China and other regions were calculated.

Results: Interestingly, China led with 256 new drug approvals, followed by the US (243 approvals), the EU (191 approvals), and Japan (187 approvals). Oncology, hematology, and infectiology were identified as the leading therapeutic areas globally and in China. Notably, PD-1 and EGFR inhibitors saw substantial approval, with 8 drugs each approved by the NMPA. China significantly reduced the approval timeline gap with the US and the EU since 2021, approving 15 first-in-class drugs during the study period.

The authors concluded, that despite the COVID-19 years, Chinese biotech has rapidly innovated in the biotech space and made up for the time gaps with increased research productivity.

Number of drug approvals by regulatory agency. Source: Yan Y, Guo X, Li Z, Shi W, Long M, Yue X, Kong F, Zhao Z. New Drug Approvals in China: An International Comparative Analysis, 2019-2023. Drug Des Devel Ther. 2025 Apr 3;19:2629-2639. doi: 10.2147/DDDT.S514132.

A comparison of drug approvals in US and China, as percentage of clinical use in various disease states. Source: Yan Y, Guo X, Li Z, Shi W, Long M, Yue X, Kong F, Zhao Z. New Drug Approvals in China: An International Comparative Analysis, 2019-2023. Drug Des Devel Ther. 2025 Apr 3;19:2629-2639. doi: 10.2147/DDDT.S514132.

China Biotech Innovation Hubs

The following was generated by Google AI

China has several prominent biotech innovation hubs, with the Yangtze River Delta region (including Shanghai, Suzhou, and Hangzhou) and Beijing being particularly strong. These regions leverage strong academic and research institutions, high R&D expenditures, and significant investment to foster a vibrant biotech ecosystem. 

Here’s a closer look at some key hubs:

Yangtze River Delta:

  • Shanghai:
    A major hub with a focus on oncology, cell and gene therapy, and a strong track record of biotech IPOs. It’s home to the Zhangjiang Biotech and Pharmaceutical Base, known as China’s “Medicine Valley”. 
  • Suzhou:
    Known for the BioBay industrial park, which houses numerous biotechnology and technology companies. 
  • Hangzhou:
    Features a growing biotech sector, with companies like Hangzhou DAC Biotech

Other Notable Hubs:

Key Factors Driving Growth:

  • Strong government support and investment:
    China has been actively promoting the growth of its biotech sector through various initiatives and funding programs. 
  • High R&D expenditures:
    China is investing heavily in research and development, particularly in the tech, manufacturing, and biotech sectors. 
  • Increasingly strong talent pool:
    China is producing a growing number of STEM graduates and globally recognized researchers. 
  • AI and technology integration:
    AI is being applied to drug design and discovery, accelerating innovation. 
  • Focus on specific areas:
    Different hubs are specializing in areas like oncology, regenerative medicine, and medical devices. 

Overall, China’s biotech sector is experiencing rapid growth and is becoming a significant player in the global landscape, with these hubs leading the way. 

 

Articles of Interest on International Biotech Venture Investment on the Open Access Scientific Journal Include:

10th annual World Medical Innovation Forum (WMIF) Monday, Sept. 23–Wednesday, Sept. 25 at the Encore Boston Harbor in Boston

CAR T-Cell Therapy Market: 2020 – 2027 – Global Market Analysis and Industry Forecast

2021 Virtual World Medical Innovation Forum, Mass General Brigham, Gene and Cell Therapy, VIRTUAL May 19–21, 2021

Real Time Coverage @BIOConvention #BIO2019: What’s Next: The Landscape of Innovation in 2019 and Beyond. 3-4 PM June 3 Philadelphia PA

 

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Bridging the Gender Gap in Healthcare: Unlocking Biopharma’s Potential in Women’s Health

Curator: Dr. Sudipta Saha, Ph.D.

Nearly half of the global population—and 80 percent of patients in therapeutic areas such as immunology—are women. Yet, treatments are frequently developed without tailored insights for female patients, often ignoring critical biological differences such as hormonal impacts, genetic factors, and cellular sex. Historically, women’s health has been narrowly defined through the lens of reproductive organs, while for non-reproductive conditions, women were treated as “small men.” This lack of focus on sex-specific biology has contributed to significant gaps in healthcare.

A recent analysis found that women spend 25 percent more of their lives in poor health compared with men due to the absence of sex-based treatments. Addressing this disparity could not only improve women’s quality of life but also unlock over $1 trillion in annual global GDP by 2040.

Four key factors contribute to the women’s health gap: limited understanding of sex-based biological differences, healthcare systems designed around male physiology, incomplete data that underestimates women’s disease burden, and chronic underfunding of female-focused research. For instance, despite women representing 78 percent of U.S. rheumatoid arthritis patients, only 7 percent of related NIH funding in 2019 targeted female-specific studies.

However, change is happening. Companies have demonstrated how targeted R&D can drive better outcomes for women. These therapies achieved expanded FDA approvals after clinical trials revealed their unique benefits for female patients. Similarly, addressing sex-based treatment gaps in asthma, atrial fibrillation, and tuberculosis could prevent millions of disability-adjusted life years.

By closing the women’s health gap, biopharma companies can drive innovation, improve therapeutic outcomes, and build high-growth markets while addressing long-standing inequities. This untapped opportunity holds the potential to transform global health outcomes for women and create a more equitable future.

References

https://www.mckinsey.com/industries/life-sciences/our-insights/closing-the-womens-health-gap-biopharmas-untapped-opportunity?stcr=97136BA6BDD64C2396A57E9487438CC6

https://www.weforum.org

https://www.nih.gov

https://www.fda.gov

https://www.who.int

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The Health Care Dossier on Clarivate PLC: How Cortellis Is Changing the Life Sciences Industry

Curator: Stephen J. Williams, Ph.D.

Source: https://en.wikipedia.org/wiki/Clarivate 

Clarivate Plc is a British-American publicly traded analytics company that operates a collection of subscription-based services, in the areas of bibliometrics and scientometricsbusiness / market intelligence, and competitive profiling for pharmacy and biotechpatents, and regulatory compliancetrademark protection, and domain and brand protection. In the academy and the scientific community, Clarivate is known for being the company that calculates the impact factor,[4] using data from its Web of Science product family, that also includes services/applications such as PublonsEndNoteEndNote Click, and ScholarOne. Its other product families are Cortellis, DRG, CPA Global, Derwent, MarkMonitor, CompuMark, and Darts-ip, [3] and also the various ProQuest products and services.

Clarivate was formed in 2016, following the acquisition of Thomson Reuters‘ Intellectual Property and Science business by Onex Corporation and Baring Private Equity Asia. Clarivate has acquired various companies since then, including, notably, ProQuest in 2021.

Further information: Thomson Scientific

Clarivate (formerly CPA Global) was formerly the Intellectual Property and Science division of Thomson Reuters. Before 2008, it was known as Thomson Scientific. In 2016, Thomson Reuters struck a $3.55 billion deal in which they spun it off as an independent company, and sold it to private-equity firms Onex Corporation and Baring Private Equity Asia.

In May 2019, Clarivate merged with the Churchill Capital Corp SPAC to obtain a public listing on the New York Stock Exchange (NYSE) It currently trades with symbol NYSE:CLVT.

Acquisitions

  • June 1, 2017: Publons, a platform for researchers to share recognition for peer review.
  • April 10, 2018: Kopernio, AI-tech startup providing ability to search for full-text versions of selected scientific journal articles.
  • October 30, 2018: TrademarkVision, provider of Artificial Intelligence (AI) trademark research applications.
  • September 9, 2019: SequenceBase, provider of patent sequence information and search technology to the biotech, pharmaceutical and chemical industries.
  • December 2, 2019: Darts-ip, provider of case law data and analytics for intellectual property (IP) professionals.
  • January 17, 2020: Decision Resources Group (DRG), a leading healthcare research and consulting company, providing high-value healthcare industry analysis and insights.
  • June 22, 2020: CustomersFirst Now, in intellectual property (“IP”) software and tech-enabled services.
  • October 1, 2020: CPA Global, intellectual property (“IP”) software and tech-enabled services.
  • December 1, 2021: ProQuest, software, data and analytics provider to academic, research and national institutions.[27]It was acquired for $5.3 billion from Cambridge Information Group in what was described as a “huge deal in the library and information publishing world”. The company said that the operational concept behind the acquisition was integrating ProQuest’s products and applications with Web of Science. Chairman of ProQuest Andy Snyder became the vice chairman of Clarivate. The Scholarly Publishing and Academic Resources Coalition, an advocacy group for open access to scholarship, voiced antitrust concerns. The acquisition had been delayed mid-year due to a Federal Trade Commission antitrust probe.

Divestments

How Clarivate Has Changed Since 2019

2019 Strategy

From 2019 Manager Discussion Yearly Report

We are a leading global information services and analytics company serving the scientific research, intellectual property and life sciences end-markets. We provide structured information and analytics to facilitate the discovery, protection and commercialization of scientific research, innovations and brands.  Our product porfolio includes well-established market-leading brands such as Web of Science, Derwent Innovation, Life Sciences, CompuMark and MarkMonitor (which they later divested).  We believe that the stron balue proposition of our content, user interfaces, visualization and analytical tools, combined with the integration of our products and services into customers’ daily workflows, leads to our substantial customer loyalty as evidenced by their willingness to renew subscriptions with us.

Our structure, enabling a sharp focus on cross-selling opportunities within markets, is comprised of two product groups:

  • Science Group: consists of Web of Science and Life Science Product Lines
  • Intellectual Property Group: consists of Derwent, CompuMark and MarkMonitor

Corporations, government agencies, universities, law firms depend on our high-value curated content, analytics and services.  Unstructured data has grown exponentially over the last decade.  The trend has resulted in a critical need for unstructured data to be meaningfully filtered, analyzed and curated into relvent information that facilitates key operational and strategic decision making.  Our highly curated, proprietary information created through our sourcing, aggregation, verification, translation, and categorization (ONTOLOGY) of data has resulted in our solutions being embedded in our customers’ workflow and decision-making processes.

Overview of Clarivate PLC five year strategy in 2019. Note that in 2019 the Science Group accounted for 56.2% of revenue! This was driven by their product Cortellis!

Figure.  Overview of Clarivate PLC five year strategy in 2019. Note that in 2019 the Science Group accounted for 56.2% of revenue! This was driven by their product Cortellis!

Also Note nowhere in the M&A Discussion in years before 2023 was anything mentioned concerning AI or Large Language Models.

The Clarivate of Today:  Built for Life Sciences with Cortellis

Clarivate PLC has integrated multiple platforms into their offering Cortellis, which integrated AI and LLM into the structured knowledge bases (see more at https://clarivate.com/products/cortellis-family/)

“Life sciences organizations are tasked, now more than ever, to discover and develop treatments that challenge the status quo, increase ROI, and improve patient lives. However, its become increasingly difficult to find, integrate and analyze the key data your teams need to make critical decisions and get your Cortellis products to patients faster.

The Cortellis solutions help research and developmentportfolio strategy and business development, and regulatory and compliance professionals gather and assess the information you need to discover innovative drugs, differentiate your treatments, and increase chances of successful regulatory approval.

Some of Cortellis solutions include:

  1. Cortellis Competitive Intelligence: maximize ROI and improve patient outcomes
  2. Cortellis Deals Intelligence: Portfolio Strategy and Business Development (find best deal)
  3. Cortellis Clinical Intelligence: Clinical Trial Support and Regulatory
  4. Cortellis Digital Health Intelligence: understand digital health ecosystem
  5. Cortellis Drug Discovery: improve drug development speed and efficiency
  6. MetaBase and MetaCore: integrated omics knowledge bases for drug discovery
  7. Cortellis Regulatory: help with filings
  8. Cortellis HTA: health tech compliance (HIPAA)
  9. CMC Intelligence: new drug marketing
  10. Generics Intelligence
  11. Drug Safety Intelligence: both preclinical safety and post marketing pharmacovigilence

Watch Videos on Cortellis for Drug Discovery

Watch Video on Qiagen Site to see how Cortellis Integrates with Qiagen Omics Platform IPA with Clarivate Meta Core to gain more insights into genomic and proteomic data

https://digitalinsights.qiagen.com/products-overview/discovery-insights-portfolio/analysis-and-visualization/qiagen-ipa/?cmpid=QDI_GA_Comp&gad_source=2&gclid=EAIaIQobChMIwu6HtvHGhQMVnZ9aBR1iCgHTEAEYASAAEgJiWPD_BwE

From the Qiagen website on Ingenuity Pathway Analysis: https://digitalinsights.qiagen.com/products-overview/discovery-insights-portfolio/analysis-and-visualization/qiagen-ipa/ 

Understand complex ‘omics data to accelerate your research

Discover why QIAGEN Ingenuity Pathway Analysis (IPA) is the leading pathway analysis application among the life science research community and is cited in tens of thousands of articles for the analysis, integration and interpretation of data derived from ‘omics experiments. Such experiments include:

  • RNA-seq
  • Small RNA-seq
  • Metabolomics
  • Proteomics
  • Microarrays including miRNA and SNP
  • Small-scale experiments

With QIAGEN IPA you can predict downstream effects and identify new targets or candidate biomarkers. QIAGEN Ingenuity Pathway Analysis helps you perform insightful data analysis and interpretation to understand your experimental results within the context of various biological systems.

Articles Relevant to Drug Development, Natural Language Processing in Drug Development, and Clarivate on this Open Access Scientific Journal Include:

The Use of ChatGPT in the World of BioInformatics and Cancer Research and Development of BioGPT by MIT

From High-Throughput Assay to Systems Biology: New Tools for Drug Discovery

Medical Startups – Artificial Intelligence (AI) Startups in Healthcare

New York Academy of Sciences Symposium: The New Wave of AI in Healthcare 2024. May 1-2, 2024 New York City, NY

Clarivate Analytics – a Powerhouse in IP assets and in Pharmaceuticals Informercials

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Live Notes from JP Morgan Healthcare Conference Virtual Endpoints Preview: January 8-9 2024

Reporter: Stephen J. Williams, Ph.D.

Endpoints at #JPM24 | Primed to unlock biopharma’s next dealmaking wave
Endpoints at JP Morgan Healthcare Conference
January 8-9 | San Francisco, CA80 Mission St, San Francisco, CA

An oasis has emerged in the biopharma money desert as backers look to replenish capital — still, uncertainty remains on whether it’s a mirage or the much needed dealmaking bump the industry needs. Yet spirits run high as JPM24 marks the triumphant return of inking strategic alliances and peering into the industry crystal ball — while keeping an eye out for some major M&A.

We’re back live from San Francisco for JPM Monday and Tuesday — our calendar of can’t-miss panels and fireside chats will feature prominent biopharma leaders to watch. The Endpoints Hub provides the ultimate coworking space with everything you need — 1:1 and group meeting spots plus guest pass capabilities and more. Join us in-person at the Endpoints Hub or watch online to stay plugged into all the action.

8 JAN
Welcome remarks
8:05 AM – 8:25 AM PST
Pfizer vet Mikael Dolsten has some thoughts on Big Pharma R&D

Endpoints News founding editor John Carroll will sit down with longtime Pfizer CSO Mikael Dolsten to talk about Pfizer’s pipeline, what he’s learned on the job about preclinical research and development and what’s ahead for the pharma giant in drug development and deals.

Mikael Dolsten

Chief Scientific Officer, President, Pfizer Research & Development

Pfizer

Pfizer Mikael Dolsten: Pfizer produced a series of AI generated molecules with new properties. Sees rapid adoption of AI in the area of drug discovery and molecular design.

 
 
8:25 AM – 9:05 AM PST
What pharma wants: The industry’s dealmakers look ahead at 2024

The drug industry’s appetite for new assets hasn’t slowed down. Top business development execs will give their outlook on the year, what they’re looking for and how they see the market.

Glenn Hunzinger

Pharmaceutical & Life Sciences Consulting Solutions Leader

PwC US

Rachna Khosla

SVP, Head of Business Development

Amgen

James Sabry

Global Head of Pharma Partnering

Roche

Devang Bhuva

SVP, Corporate Development

Gilead Sciences, Inc.

Endpoints News

Dealmaking panel

Glenn Hunzinger: if you do not have a GLP1 will have a tough time getting a good market price for your company; capital markets are not where they want to be; sees a tough deal making climate like last year.  The problem with many biotech companies are they are coming earlier to the venture capital because of greater funding needs and so it is imperative that they articulate the potential of their company in scientific detail

Rachna Khosla:  Make sure your investors are not just CAPITAL PARTNERS but use their expertise and involve them in development issues you may have, especially ones that a young firm will face.  The problem is most investments assume what the future looks like (for example how antibody drug conjugates, once a field left for dead, has been rejuvenated because of advances in chemistry). 

James Sabry: noted that cardiac and metabolic drugs are now at the focus of many investors, especially with the new anti-obesity drugs on market

Devang Bhuva: Most deals we see start as collaborations or partnerships.  You want to involve an alliance management team early in the deal making process.  This process could take years.

 
9:05 AM – 9:20 AM PST
The IPO: How Apogee Therapeutics went public in the most challenging market in years

Not many biotechs went public in 2023. And of those that did, not many have had a great time of it. Apogee is the exception and our panel will offer a behind-the-scenes look at their decision to enter the market and what life is like as a young public company.

Michael Henderson

CEO

Apogee Therapeutics

Kyle LaHucik

MODERATOR

Senior Reporter

Endpoints News

Michael Henderson:  Not many biotech IPOs deals happened in 2023.  Michael feels it is because too many biotechs focused on building platforms, which was a hard sell in 2023.  He felt not many biotechs had clear milestones and investors wanted a clear primary validated target.  He said many biotech startups are in a funding crunch and most need at least $440M on their balance sheet to get to 2026.

9:50 AM – 10:10 AM PST
Top predictions for biotech in 2024

Catalent CEO Alessandro Maselli will be back at the big JPM healthcare confab to talk with Endpoints News founder John Carroll about their top predictions of what’s coming up for the biotech industry in 2024. The stakes couldn’t be higher as the industry grapples with headwinds and new opportunities in a gale of market forces. Two top observers share their thoughts on the year ahead.

Alessandro Maselli

President & CEO

Catalent

10:15 AM – 10:35 AM PST
Innovation at a crossroads: Keys to unlocking the value of science and technology

The industry has long discussed the promise of technology and the acceleration it provides in scientific advancement and across the industry value chain. However, the promise of its impact has yet to fully be realized. This discussion will outline the keys to unleashing this promise and the implications and actions to be taken by the biopharmaceutical companies across the industry.

Ray Pressburger

North America Life Sciences Industry Lead & Global Life Sciences Strategy Lead

Accenture

SPONSORED BY

10:35 AM – 11:05 AM PST
Activism and Investing: In conversation with Elliott Investment Management’s Marc Steinberg

Elliott has been behind many of 2023’s highest-profile healthcare investments, including multiple activist engagements and taking Syneos Health private. What has made large healthcare companies such interesting investment opportunities for firms like Elliott? What’s Elliott’s investing strategy in healthcare? And what should companies expect when an activist calls?

Marc Steinberg

Senior Portfolio Manager

Elliott Investment Management

Andrew Dunn

MODERATOR

Biopharma Correspondent

Endpoints News

11:05 AM – 11:35 AM PST
Creating ROI from AI

AI is predicted to transform the way drugs are made, from discovery to clinical trials to market. But beyond the initial hype and early adoption, where has AI made meaningful contributions to R&D? How does it help drug developers advance science? Endpoints publisher Arsalan Arif is convening a panel of leading experts to discuss the state of AI in the pharmaceutical landscape and the outlook for 2024. How does AI impact the drug pipeline, from the early steps of discovery to reducing trial failure rate?

Thomas Clozel

Co-Founder & CEO

Owkin

Venkat Sethuraman

SVP, Global Biometrics & Data Sciences

Bristol Myers Squibb

Frank O. Nestle

Global Head of Research & Chief Scientific Officer

Sanofi

Matthias Evers

Chief Business Officer

Evotec

Arsalan Arif

MODERATOR

Founder & Publisher

Endpoints News

SPONSORED BY

11:35 AM – 12:00 PM PST
Biopharma’s dealmaker: Behind the scenes with Centerview Partners co-president Eric Tokat

Almost every major biopharma deal in 2023 had Centerview’s name attached to it. And much of the time, Eric Tokat was the banker making those deals happen. Hear his outlook for 2024, how transactions are getting done and what’s placed his firm at the center of so much action.

E. Eric Tokat

Co-President, Investment Banking

Centerview Partners

CenterView Partners Eric Tokat feels dealmaking will improve in 2024, given the recent flurry of dealmaking at end of last year and right before main JPM Healthcare Conference.  He says Centerview wants to help the biotechs they invest in on their strategic path.  This may translate into buyers more actively involved (more than startups want) and buyers now are in the drivers seat as far as the timeline of deals and development.

Is the megamerger dead for this year?  He says it is very hard to see two major mergers happening but there will be many smaller and mid size biotech deals happening, but these deals will be more speculative in nature..  The focus for large pharma is top line growth.  Most of the buyers have an infrastructure and value is more of buying and dropping it in their business so there is now a huge emphasis on due diligence on whether synergies exist or not

 
12:00 PM – 12:30 PM PST
Founder, legend, leader: In conversation with Nobel laureate Carolyn Bertozzi

Carolyn Bertozzi’s discoveries around bioorthogonal chemistry won the Nobel Prize in Chemistry in 2022 and are at the heart of new therapies being tested in patients. Join us as we discuss what inspires her and where she sees the next big advances.

Carolyn Bertozzi

Prof. of Chemistry, Stanford University and Baker Family Director of Sarafan ChEM-H

Stanford University

Nicole DeFeudis

MODERATOR

Editor

Endpoints News

Bioorthogonal chemistry: class of high yielding chemical reactions that proceed rapidly and selectively in biological environments without side reactions toward endogenous functions.  This is also a type of ‘click chemistry’ in biological system where only specifically alter the biomolecule of interest.

Orthogonal: two chemicals not interacting with each other

Dr. Bertozzi noted she has started a new Antibody-Drug-Conjugate (ADC) company which involves designing with biorthogonal chemistry to make new functional molecules with varying properties

She noted hardly any biologists knew anything about glycobiology when she first started.  However now she feels pharma and academia are working very well with each other

Bioorthogonal and Click Chemistry
Curated by Prof. Carolyn R. Bertozzi, 2022 winner of the Nobel Prize in Chemistry

Source: https://pubs.acs.org/page/vi/bioorthogonal-click-chemistry

The 2022 Nobel Prize in Chemistry has been awarded jointly to ACS Central Science Editor-in-Chief, Carolyn R. Bertozzi of Stanford University, Morten Meldal of the University of Copenhagen, and K. Barry Sharpless of Scripps Research, for the development of click chemistry and bioorthogonal chemistry.

To celebrate this remarkable achievement, 2022 Nobel Prize winner Professor Carolyn R. Bertozzi has curated this Bioorthogonal and Click Chemistry Virtual Issue, highlighting papers published across ACS journals that have built upon the foundational work in this exciting area of chemistry.

From Mechanism to Mouse: A Tale of Two Bioorthogonal Reactions

Ellen M. Sletten and Carolyn R. Bertozzi* Acc. Chem. Res. 2011, 44, 9, 666-676 August 15, 2011

Abstract

Bioorthogonal reactions are chemical reactions that neither interact with nor interfere with a biological system. The participating functional groups must be inert to biological moieties, must selectively reactive with each other under biocompatible conditions, and, for in vivo applications, must be nontoxic to cells and organisms. Additionally, it is helpful if one reactive group is small and therefore minimally perturbing of a biomolecule into which it has been introduced either chemically or biosynthetically. Examples from the past decade suggest that a promising strategy for bioorthogonal reaction development begins with an analysis of functional group and reactivity space outside those defined by nature. Issues such as stability of reactants and products (particularly in water), kinetics, and unwanted side reactivity with biofunctionalities must be addressed, ideally guided by detailed mechanistic studies. Finally, the reaction must be tested in a variety of environments, escalating from aqueous media to biomolecule solutions to cultured cells and, for the most optimized transformations, to live organisms.

9 JAN

9:40 AM – 10:10 AM PST

Biotech downturn survival school

Our panelists have seen the worst, and made it through to the other side. Join us for downturn survival school as our panelists talk about what sets apart the ones who make it through tough times.

These panalists think it will be specialist capital year to shine while the general capital is still sitting on the sidelines

JJ Kang

CEO

Appia Bio

“2023 was a tough year while 2020 was a boon year to start a company.  We will continue to see these cycles; many of these new CEOs have never seen a biotech downturn yet and may not know how to preserve capital for the downturn”.

“Doing a partnership with Kite Pharmaceuticals early in our startp allowed us to get work done without risking a lot of capital, even if it means equity and asset dilution.  That makes sense. However even if you are small insist on being an equal partner.”

“There are many investors we talk to who do not want to invest in cell therapy.  Too risky now”

Carl Gordon

Managing Partner

OrbiMed Advisors

There are many macroeconomic factors affecting investment and capital today which will carry on through 2024.   Not raising money when you do not need money is a bad philosophy.  Always bbe raising captial.  This is especially true when you have to rely on hedge funds.  Parnerships howeve are sometimes the only way for small biotechs to leverage their strengths.

Joshua Boger

Executive Chair

Alkeus Pharmaceuticals, Inc.

Boger: Expect volatility for 2024.  This environment feels very different than past downturns.

Even in downturns there is still lots of capital; remember access to human capital is better in a downturn and is easier to access;  however it has become harder to get drug approvals

The panelists agree that access to capital and funding will be as tricky in 2024 than 2023.  They did

suggest that a new funding avenue, private credit, may be a source of capital.  This is discussed below:

When thinking about a private alternative investment asset class, the first thing that springs to mind is private equity. But there’s one more asset class with the word private in its name that has recently gained much attention. We’re talking about private credit

Indeed, this once little-known investment strategy is now growing rapidly in popularity, offering private investors worldwide an exciting opportunity to diversify their portfolio with, in theory, less risky investments that yield significant returns. 

  • Private credit investments refer to investors lending money to companies who then repay the loan at a given interest rate within the predetermined period.
  • The private credit market has grown significantly over the past years, rising from $875 million in 2020 to $1.4 trillion at the beginning of 2023. 

Please WATCH VIDEO BY GOLDMAN SACHS ON PRIVATE CREDIT

 

 

 

 

10:50 AM – 11:20 AM PST

The New Molecule: How breakthrough technologies are actually changing pharma R&D

Join us for a look at how AI, machine learning and generative technologies are actually being applied inside drugmakers’ labs. We’ll explore how new technologies are being used, their implications, how they intersect with regulatory and IP issues and how this fast-changing field is likely to evolve.

Kailash Swarna

Managing Director & Global Life Sciences Clinical Development Lead

Accenture

Artificial Intelligence is making impact in a grand way on biology in three aspects:

  1. Speeding up target validation: now we can get through 300 molecules a day
  2. Predicition like AlphaFold is doing; molecular simulations
  3. Document submission especially with regulatory and IND submissions

Pamela Carroll

COO

Isomorphic Labs formerly of AlphaFold

We were first with Novartis at last year JPM and was one year old but parnering with them in that initial year was very important for sealing the deal.

They are looking now at neurologic diseases like ALS.  She wondered whether ALS is actually multiple diseases and we need to stratify patients like we do in oncology trials.  Their main competion is the whole tech world like Amazon, Google and other Machine Learning companies so being a tech player in the biotech world means you are not just competing with other biotechs but large tech companies as well.

Jorge Conde

General Partner

Andreessen Horowitz

Need is still great for drug discovery; early adopters show AI tools can be used in big pharma. There are lots of applications of AI in managing care; a lot of back office applications including patient triaging.  He does not see big AI mergers with pharma companies –  this will be mainly partnerships not M&A deals

Alicyn Campbell

Chief Scientific Officer

Evinova, a Healthtech Subsidiary of the AstraZeneca Group

There is a need to turn AI for real world example.  For example AI tools were used in clinical trials to determine patient cohorts with pneumonitis.  At Evinova they are determining how AI can hel[p show clinical benefit with respect to efficacy and safety

Joshua Boger at #JPM24 (Brian Benton Photography)

  January 12, 2024 09:06 AM ESTUpdated 10:00 AM PeopleStartups

Vertex founder Joshua Boger on surviving downturns, ‘painful’ partnerships, and the importance of culture: #JPM24

Andrew Dunn

Biopharma Correspondent

Source: https://endpts.com/jpm24-vertex-founder-joshua-boger-on-surviving-downturns-painful-partnerships-and-the-importance-of-culture/

While the JP Morgan Healthcare Conference was full of voices of measured optimism, rooting for the market to bounce back in 2024, one longtime biotech leader warned against setting any firm expectations.

Instead of predicting when the downturn may end, Vertex Pharmaceuticals founder Joshua Boger said he advises biotech leaders to expect — and plan for — volatility. Speaking Tuesday on an Endpoints News panel alongside OrbiMed’s Carl Gordon and Appia Bio CEO JJ Kang, Boger shared lessons learned on surviving downturns, striking pharma deals, and the importance of keeping a company’s culture based on his two decades of founding and leading Vertex as CEO from 1989 to 2009. The 72-year-old is now serving as executive chairman of Alkeus Pharmaceuticals, a startup developing a rare disease drug.

“I never experienced a straight line up,” Boger said. “Everything had its cycles, and it was how you respond to the cycle, not by predicting when the end is going to be, but just by responding to the present situation.”

At Boger’s first appearance at the JP Morgan conference in 1991, he said the conference’s theme was the end of biotech financing. Just a few months later, Regeneron successfully went public, rapidly changing the outlook for the whole field.

“We had no idea we were ever going to take public money,” he said. “When Regeneron did their IPO, we went, ‘Whoa, there’s something happening here,’ and we pivoted quickly.”

Vertex went public later that year. Throughout his 20-year tenure, Boger said no pharma company ever made an acquisition offer for Vertex, which now commands a market value of $110 billion and recently won the first FDA approval for a CRISPR gene editing therapy.

“We had an uber corporate policy to always make ourselves more expensive than anyone would stomach,” Boger said.

However, Vertex did strike a range of partnerships with Big Pharmas, which Boger described as a painful but necessary part of running a biotech startup.

“It’s impossible for a partnership not to slow you down,” he said. “You can and should try as hard as you can not to do that, but just count on it. They’ll slow you down.”

Boger said startups should insist on being equal partners in pharma deals, at least making sure they have a seat at a partner’s development meetings.

“Realize they’re going to be painful, it’s going to be horrible, and you need to do it,” Boger said.

While Vertex suffered through layoffs, stock price plunges, and trial failures, Boger credited a focus on culture as key to its long-term success.

“It’s the most important ingredient for a successful company,” he said. “Technology is acquirable. Culture is not acquirable. There are 10 companies that will fail because of culture for every one that succeeds, and the successful companies in retrospect will almost always have special cultural aspects that kept them through those downtimes.”

JPM24 opens with ADCs the hottest ticket in San Francisco

By Annalee ArmstrongJan 8, 2024 6:30am

Source: https://www.fiercebiotech.com/biotech/jpm24-opens-adcs-hottest-ticket-san-francisco

The overall deal flow in biopharma tapered off in 2023 but the big companies sure know what they want (what they really, really want), according to a new report from J.P. Morgan.

And that’s antibody-drug conjugates, which drove a fourth-quarter spike in licensing deal proceeds and provided a glimmer of hope to an industry battered by outside forces and grim financing prospects.

J.P. Morgan’s annual 2023 Biopharma Licensing and Venture Report arrived on the eve of the firm’s famous conference, which is set to welcome thousands of attendees in San Francisco today—East Coast weather permitting.

2023 was tough, but clinical biotechs still had a lot of opportunities to wheel and deal, according to J.P. Morgan. While licensing deals, venture investments, M&A and IPOs were down overall in the fourth quarter, deal values stayed fairly high thanks to a flurry of late-stage tie ups.

Follow the Fierce team’s coverage of the 2024 J.P. Morgan Healthcare Conference here

Biopharma licensing partnerships accounted for $63 billion in total value during the fourth quarter from 108 deals. Just one deal—Merck’s ADC partnership with Daiichi Sankyo—accounted for $22 billion of that. Another huge one was another ADC bet, with Bristol Myers Squibb signing on to work with SystImmune for a total value of $8.4 billion. If you exclude the Merck deal, the total value of these partnerships is still higher than the previous quarter, which ended with $32.1 billion.

The total number of licensing deals compares to 149 in the same quarter a year earlier, 195 for Q4 2021 and 223 for Q4 2022.

As for venture investments, the year closed out with $17 billion total across 250 rounds, thanks to $3.5 billion earned through 79 rounds in the last quarter. Aiolos Bio snagged the title of largest venture round of the quarter with $245 million, which also proved to be the largest series A, too.

There was just one IPO in all of the fourth quarter—Cargo Therapeutics making the plunge for $300 million—and 13 overall for the year. It’s a far cry from the heyday of 2021 and experts are still unsure what 2024 will hold. J.P. Morgan reported $2.5 billion raised from 12 completed biopharma IPOs for the year on Nasdaq and NYSE. Nine out of the 12 companies had clinical programs when they took the leap to the public markets. As of December 13, five of the companies were trading above their IPO price.

As for M&A, December saw a rush of Big Pharmas snapping up companies around Christmas. J.P. Morgan tallied the fourth quarter at $37.6 billion and $128.8 billion across 112 total acquisitions for all of 2023.

AbbVie was the top buyer of the quarter with the two largest acquisitions thanks to the $10 billion outlay for ImmunoGen and $8.7 billion buy of Cerevel Therapeutics.

All of this adds up to 270 total deals in the fourth quarter total, which is lower than the third quarter which exceeded 300.

J.P. Morgan sees some big potential for smaller biopharmas looking for licensing partners, as Big Pharmas have been handing out larger upfront payments for the deals they really want.

Cancer was once again the most in-demand therapeutic areas, reaching a new height of $86.1 billion in 2023. Followed by $21.1 billion for neurological disorders.

For More Articles on Real Time Conference Coverage in this Open Access Scientific Journal see:

Part One: The Process of Real Time Coverage using Social Media

Part Two: List of BioTech Conferences 2013 to Present

https://worldmedicalinnovation.org/

https://pharmaceuticalintelligence.com/2022/05/01/2022-world-medical-innovation-forum-gene-cell-therapy-may-2-4-2022-boston-in-person/

 

https://event.technologyreview.com/emtech-digital-2022/agenda-overview

 

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Eight Subcellular Pathologies driving Chronic Metabolic Diseases – Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics: Impact on Pharmaceuticals in Use

Eight Subcellular Pathologies driving Chronic Metabolic Diseases – Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics: Impact on Pharmaceuticals in Use

Curators:

 

THE VOICE of Aviva Lev-Ari, PhD, RN

In this curation we wish to present two breaking through goals:

Goal 1:

Exposition of a new direction of research leading to a more comprehensive understanding of Metabolic Dysfunctional Diseases that are implicated in effecting the emergence of the two leading causes of human mortality in the World in 2023: (a) Cardiovascular Diseases, and (b) Cancer

Goal 2:

Development of Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics for these eight subcellular causes of chronic metabolic diseases. It is anticipated that it will have a potential impact on the future of Pharmaceuticals to be used, a change from the present time current treatment protocols for Metabolic Dysfunctional Diseases.

According to Dr. Robert Lustig, M.D, an American pediatric endocrinologist. He is Professor emeritus of Pediatrics in the Division of Endocrinology at the University of California, San Francisco, where he specialized in neuroendocrinology and childhood obesity, there are eight subcellular pathologies that drive chronic metabolic diseases.

These eight subcellular pathologies can’t be measured at present time.

In this curation we will attempt to explore methods of measurement for each of these eight pathologies by harnessing the promise of the emerging field known as Bioelectronics.

Unmeasurable eight subcellular pathologies that drive chronic metabolic diseases

  1. Glycation
  2. Oxidative Stress
  3. Mitochondrial dysfunction [beta-oxidation Ac CoA malonyl fatty acid]
  4. Insulin resistance/sensitive [more important than BMI], known as a driver to cancer development
  5. Membrane instability
  6. Inflammation in the gut [mucin layer and tight junctions]
  7. Epigenetics/Methylation
  8. Autophagy [AMPKbeta1 improvement in health span]

Diseases that are not Diseases: no drugs for them, only diet modification will help

Image source

Robert Lustig, M.D. on the Subcellular Processes That Belie Chronic Disease

https://www.youtube.com/watch?v=Ee_uoxuQo0I

 

Exercise will not undo Unhealthy Diet

Image source

Robert Lustig, M.D. on the Subcellular Processes That Belie Chronic Disease

https://www.youtube.com/watch?v=Ee_uoxuQo0I

 

These eight Subcellular Pathologies driving Chronic Metabolic Diseases are becoming our focus for exploration of the promise of Bioelectronics for two pursuits:

  1. Will Bioelectronics be deemed helpful in measurement of each of the eight pathological processes that underlie and that drive the chronic metabolic syndrome(s) and disease(s)?
  2. IF we will be able to suggest new measurements to currently unmeasurable health harming processes THEN we will attempt to conceptualize new therapeutic targets and new modalities for therapeutics delivery – WE ARE HOPEFUL

In the Bioelecronics domain we are inspired by the work of the following three research sources:

  1. Biological and Biomedical Electrical Engineering (B2E2) at Cornell University, School of Engineering https://www.engineering.cornell.edu/bio-electrical-engineering-0
  2. Bioelectronics Group at MIT https://bioelectronics.mit.edu/
  3. The work of Michael Levin @Tufts, The Levin Lab
Michael Levin is an American developmental and synthetic biologist at Tufts University, where he is the Vannevar Bush Distinguished Professor. Levin is a director of the Allen Discovery Center at Tufts University and Tufts Center for Regenerative and Developmental Biology. Wikipedia
Born: 1969 (age 54 years), Moscow, Russia
Education: Harvard University (1992–1996), Tufts University (1988–1992)
Affiliation: University of Cape Town
Research interests: Allergy, Immunology, Cross Cultural Communication
Awards: Cozzarelli prize (2020)
Doctoral advisor: Clifford Tabin
Most recent 20 Publications by Michael Levin, PhD
SOURCE
SCHOLARLY ARTICLE
The nonlinearity of regulation in biological networks
1 Dec 2023npj Systems Biology and Applications9(1)
Co-authorsManicka S, Johnson K, Levin M
SCHOLARLY ARTICLE
Toward an ethics of autopoietic technology: Stress, care, and intelligence
1 Sep 2023BioSystems231
Co-authorsWitkowski O, Doctor T, Solomonova E
SCHOLARLY ARTICLE
Closing the Loop on Morphogenesis: A Mathematical Model of Morphogenesis by Closed-Loop Reaction-Diffusion
14 Aug 2023Frontiers in Cell and Developmental Biology11:1087650
Co-authorsGrodstein J, McMillen P, Levin M
SCHOLARLY ARTICLE
30 Jul 2023Biochim Biophys Acta Gen Subj1867(10):130440
Co-authorsCervera J, Levin M, Mafe S
SCHOLARLY ARTICLE
Regulative development as a model for origin of life and artificial life studies
1 Jul 2023BioSystems229
Co-authorsFields C, Levin M
SCHOLARLY ARTICLE
The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences
1 Jul 2023International Journal of Molecular Sciences24(13)
Co-authorsMasuelli S, Real S, McMillen P
SCHOLARLY ARTICLE
Bioelectricidad en agregados multicelulares de células no excitables- modelos biofísicos
Jun 2023Revista Española de Física32(2)
Co-authorsCervera J, Levin M, Mafé S
SCHOLARLY ARTICLE
Bioelectricity: A Multifaceted Discipline, and a Multifaceted Issue!
1 Jun 2023Bioelectricity5(2):75
Co-authorsDjamgoz MBA, Levin M
SCHOLARLY ARTICLE
Control Flow in Active Inference Systems – Part I: Classical and Quantum Formulations of Active Inference
1 Jun 2023IEEE Transactions on Molecular, Biological, and Multi-Scale Communications9(2):235-245
Co-authorsFields C, Fabrocini F, Friston K
SCHOLARLY ARTICLE
Control Flow in Active Inference Systems – Part II: Tensor Networks as General Models of Control Flow
1 Jun 2023IEEE Transactions on Molecular, Biological, and Multi-Scale Communications9(2):246-256
Co-authorsFields C, Fabrocini F, Friston K
SCHOLARLY ARTICLE
Darwin’s agential materials: evolutionary implications of multiscale competency in developmental biology
1 Jun 2023Cellular and Molecular Life Sciences80(6)
Co-authorsLevin M
SCHOLARLY ARTICLE
Morphoceuticals: Perspectives for discovery of drugs targeting anatomical control mechanisms in regenerative medicine, cancer and aging
1 Jun 2023Drug Discovery Today28(6)
Co-authorsPio-Lopez L, Levin M
SCHOLARLY ARTICLE
Cellular signaling pathways as plastic, proto-cognitive systems: Implications for biomedicine
12 May 2023Patterns4(5)
Co-authorsMathews J, Chang A, Devlin L
SCHOLARLY ARTICLE
Making and breaking symmetries in mind and life
14 Apr 2023Interface Focus13(3)
Co-authorsSafron A, Sakthivadivel DAR, Sheikhbahaee Z
SCHOLARLY ARTICLE
The scaling of goals from cellular to anatomical homeostasis: an evolutionary simulation, experiment and analysis
14 Apr 2023Interface Focus13(3)
Co-authorsPio-Lopez L, Bischof J, LaPalme JV
SCHOLARLY ARTICLE
The collective intelligence of evolution and development
Apr 2023Collective Intelligence2(2):263391372311683SAGE Publications
Co-authorsWatson R, Levin M
SCHOLARLY ARTICLE
Bioelectricity of non-excitable cells and multicellular pattern memories: Biophysical modeling
13 Mar 2023Physics Reports1004:1-31
Co-authorsCervera J, Levin M, Mafe S
SCHOLARLY ARTICLE
There’s Plenty of Room Right Here: Biological Systems as Evolved, Overloaded, Multi-Scale Machines
1 Mar 2023Biomimetics8(1)
Co-authorsBongard J, Levin M
SCHOLARLY ARTICLE
Transplantation of fragments from different planaria: A bioelectrical model for head regeneration
7 Feb 2023Journal of Theoretical Biology558
Co-authorsCervera J, Manzanares JA, Levin M
SCHOLARLY ARTICLE
Bioelectric networks: the cognitive glue enabling evolutionary scaling from physiology to mind
1 Jan 2023Animal Cognition
Co-authorsLevin M
SCHOLARLY ARTICLE
Biological Robots: Perspectives on an Emerging Interdisciplinary Field
1 Jan 2023Soft Robotics
Co-authorsBlackiston D, Kriegman S, Bongard J
SCHOLARLY ARTICLE
Cellular Competency during Development Alters Evolutionary Dynamics in an Artificial Embryogeny Model
1 Jan 2023Entropy25(1)
Co-authorsShreesha L, Levin M
5

5 total citations on Dimensions.

Article has an altmetric score of 16
SCHOLARLY ARTICLE
1 Jan 2023BIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY138(1):141
Co-authorsClawson WP, Levin M
SCHOLARLY ARTICLE
Future medicine: from molecular pathways to the collective intelligence of the body
1 Jan 2023Trends in Molecular Medicine
Co-authorsLagasse E, Levin M

THE VOICE of Dr. Justin D. Pearlman, MD, PhD, FACC

PENDING

THE VOICE of  Stephen J. Williams, PhD

Ten TakeAway Points of Dr. Lustig’s talk on role of diet on the incidence of Type II Diabetes

 

  1. 25% of US children have fatty liver
  2. Type II diabetes can be manifested from fatty live with 151 million  people worldwide affected moving up to 568 million in 7 years
  3. A common myth is diabetes due to overweight condition driving the metabolic disease
  4. There is a trend of ‘lean’ diabetes or diabetes in lean people, therefore body mass index not a reliable biomarker for risk for diabetes
  5. Thirty percent of ‘obese’ people just have high subcutaneous fat.  the visceral fat is more problematic
  6. there are people who are ‘fat’ but insulin sensitive while have growth hormone receptor defects.  Points to other issues related to metabolic state other than insulin and potentially the insulin like growth factors
  7. At any BMI some patients are insulin sensitive while some resistant
  8. Visceral fat accumulation may be more due to chronic stress condition
  9. Fructose can decrease liver mitochondrial function
  10. A methionine and choline deficient diet can lead to rapid NASH development

 

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Artificial Intelligence (AI) Used to Successfully Determine Most Likely Repurposed Antibiotic Against Deadly Superbug Acinetobacter baumanni

Reporter: Stephen J. Williams, Ph.D.

The World Health Organization has identified 3 superbugs, or infective micororganisms displaying resistance to common antibiotics and multidrug resistance, as threats to humanity:

Three bacteria were listed as critical:

  • Acinetobacter baumannii bacteria that are resistant to important antibiotics called carbapenems. Acinetobacter baumannii are highly-drug resistant bacteria that can cause a range of infections for hospitalized patients, including pneumonia, wound, or blood infections.
  • Pseudomonas aeruginosa, which are resistant to carbapenems. Pseudomonas aeruginosa can cause skin rashes and ear infectious in healthy people but also severe blood infections and pneumonia when contracted by sick people in the hospital.
  • Enterobacteriaceae — a family of bacteria that live in the human gut — that are resistant to both carbepenems and another class of antibiotics, cephalosporins.

 

It has been designated critical need for development of  antibiotics to these pathogens.  Now researchers at Mcmaster University and others in the US had used artificial intelligence (AI) to screen libraries of over 7,000 chemicals to find a drug that could be repurposed to kill off the pathogen.

Liu et. Al. (1) published their results of an AI screen to narrow down potential chemicals that could work against Acinetobacter baumanii in Nature Chemical Biology recently.

Abstract

Acinetobacter baumannii is a nosocomial Gram-negative pathogen that often displays multidrug resistance. Discovering new antibiotics against A. baumannii has proven challenging through conventional screening approaches. Fortunately, machine learning methods allow for the rapid exploration of chemical space, increasing the probability of discovering new antibacterial molecules. Here we screened ~7,500 molecules for those that inhibited the growth of A. baumannii in vitro. We trained a neural network with this growth inhibition dataset and performed in silico predictions for structurally new molecules with activity against A. baumannii. Through this approach, we discovered abaucin, an antibacterial compound with narrow-spectrum activity against A. baumannii. Further investigations revealed that abaucin perturbs lipoprotein trafficking through a mechanism involving LolE. Moreover, abaucin could control an A. baumannii infection in a mouse wound model. This work highlights the utility of machine learning in antibiotic discovery and describes a promising lead with targeted activity against a challenging Gram-negative pathogen.

Schematic workflow for incorporation of AI for antibiotic drug discovery for A. baumannii from 1. Liu, G., Catacutan, D.B., Rathod, K. et al. Deep learning-guided discovery of an antibiotic targeting Acinetobacter baumannii. Nat Chem Biol (2023). https://doi.org/10.1038/s41589-023-01349-8

Figure source: https://www.nature.com/articles/s41589-023-01349-8

Article Source: https://www.nature.com/articles/s41589-023-01349-8

  1. Liu, G., Catacutan, D.B., Rathod, K. et al.Deep learning-guided discovery of an antibiotic targeting Acinetobacter baumanniiNat Chem Biol (2023). https://doi.org/10.1038/s41589-023-01349-8

 

 

For reference to WHO and lists of most pathogenic superbugs see https://www.scientificamerican.com/article/who-releases-list-of-worlds-most-dangerous-superbugs/

The finding was first reported by the BBC.

Source: https://www.bbc.com/news/health-65709834

By James Gallagher

Health and science correspondent

Scientists have used artificial intelligence (AI) to discover a new antibiotic that can kill a deadly species of superbug.

The AI helped narrow down thousands of potential chemicals to a handful that could be tested in the laboratory.

The result was a potent, experimental antibiotic called abaucin, which will need further tests before being used.

The researchers in Canada and the US say AI has the power to massively accelerate the discovery of new drugs.

It is the latest example of how the tools of artificial intelligence can be a revolutionary force in science and medicine.

Stopping the superbugs

Antibiotics kill bacteria. However, there has been a lack of new drugs for decades and bacteria are becoming harder to treat, as they evolve resistance to the ones we have.

More than a million people a year are estimated to die from infections that resist treatment with antibiotics.The researchers focused on one of the most problematic species of bacteria – Acinetobacter baumannii, which can infect wounds and cause pneumonia.

You may not have heard of it, but it is one of the three superbugs the World Health Organization has identified as a “critical” threat.

It is often able to shrug off multiple antibiotics and is a problem in hospitals and care homes, where it can survive on surfaces and medical equipment.

Dr Jonathan Stokes, from McMaster University, describes the bug as “public enemy number one” as it’s “really common” to find cases where it is “resistant to nearly every antibiotic”.

 

Artificial intelligence

To find a new antibiotic, the researchers first had to train the AI. They took thousands of drugs where the precise chemical structure was known, and manually tested them on Acinetobacter baumannii to see which could slow it down or kill it.

This information was fed into the AI so it could learn the chemical features of drugs that could attack the problematic bacterium.

The AI was then unleashed on a list of 6,680 compounds whose effectiveness was unknown. The results – published in Nature Chemical Biology – showed it took the AI an hour and a half to produce a shortlist.

The researchers tested 240 in the laboratory, and found nine potential antibiotics. One of them was the incredibly potent antibiotic abaucin.

Laboratory experiments showed it could treat infected wounds in mice and was able to kill A. baumannii samples from patients.

However, Dr Stokes told me: “This is when the work starts.”

The next step is to perfect the drug in the laboratory and then perform clinical trials. He expects the first AI antibiotics could take until 2030 until they are available to be prescribed.

Curiously, this experimental antibiotic had no effect on other species of bacteria, and works only on A. baumannii.

Many antibiotics kill bacteria indiscriminately. The researchers believe the precision of abaucin will make it harder for drug-resistance to emerge, and could lead to fewer side-effects.

 

In principle, the AI could screen tens of millions of potential compounds – something that would be impractical to do manually.

“AI enhances the rate, and in a perfect world decreases the cost, with which we can discover these new classes of antibiotic that we desperately need,” Dr Stokes told me.

The researchers tested the principles of AI-aided antibiotic discovery in E. coli in 2020, but have now used that knowledge to focus on the big nasties. They plan to look at Staphylococcus aureus and Pseudomonas aeruginosa next.

“This finding further supports the premise that AI can significantly accelerate and expand our search for novel antibiotics,” said Prof James Collins, from the Massachusetts Institute of Technology.

He added: “I’m excited that this work shows that we can use AI to help combat problematic pathogens such as A. baumannii.”

Prof Dame Sally Davies, the former chief medical officer for England and government envoy on anti-microbial resistance, told Radio 4’s The World Tonight: “We’re onto a winner.”

She said the idea of using AI was “a big game-changer, I’m thrilled to see the work he (Dr Stokes) is doing, it will save lives”.

Other related articles and books published in this Online Scientific Journal include the following:

Series D: e-Books on BioMedicine – Metabolomics, Immunology, Infectious Diseases, Reproductive Genomic Endocrinology

(3 book series: Volume 1, 2&3, 4)

https://www.amazon.com/gp/product/B08VVWTNR4?ref_=dbs_p_pwh_rwt_anx_b_lnk&storeType=ebooks

 

 

 

 

 

 

 

 

 

 

  • The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications:

 

  • Series D, VOLUME 2

Infectious Diseases and Therapeutics

and

  • Series D, VOLUME 3

The Immune System and Therapeutics

(Series D: BioMedicine & Immunology) Kindle Edition.

On Amazon.com since September 4, 2017

(English Edition) Kindle Edition – as one Book

https://www.amazon.com/dp/B075CXHY1B $115

 

Bacterial multidrug resistance problem solved by a broad-spectrum synthetic antibiotic

The Journey of Antibiotic Discovery

FDA cleared Clever Culture Systems’ artificial intelligence tech for automated imaging, analysis and interpretation of microbiology culture plates speeding up Diagnostics

Artificial Intelligence: Genomics & Cancer

Read Full Post »

 

The Vibrant Philly Biotech Scene: Recent Happenings & Deals

Curator: Stephen J. Williams, Ph.D.

 

As the office and retail commercial real estate market has been drying up since the COVID pandemic, commercial real estate developers in the Philadelphia area have been turning to the health science industry to suit their lab space needs.  This includes refurbishing old office space as well as new construction.

Gattuso secures $290M construction loan for life sciences building on Drexel campus

Source: https://www.bizjournals.com/philadelphia/news/2022/12/19/construction-loan-gattuso-drexel-life-sciences.html?utm_source=st&utm_medium=en&utm_campaign=BN&utm_content=pl&ana=e_pl_BN&j=30034971&senddate=2022-12-20

 

By Ryan Mulligan  –  Reporter, Philadelphia Business Journal

Dec 19, 2022

Gattuso Development Partners and Vigilant Holdings of New York have secured a $290 million construction loan for a major life sciences building set to be developed on Drexel University’s campus.

The funding comes from Houston-based Corebridge Financial, with an additional equity commitment from Boston-based Baupost Group, which is also a partner on the project. JLL’s Capital Markets group arranged the loan.

Plans for the University City project at 3201 Cuthbert St. carry a price tag of $400 million. The 11-story building will total some 520,000 square feet, making it the largest life sciences research and lab space in the city when it comes online.

The building at 3201 Cuthbert will rise on what had served as a recreation field used by Drexel and is located next to the Armory. Gattuso Development, which will lease the parcel from Drexel, expects to to complete the project by fall 2024. Robert A.M. Stern Architects designed the building.

 

A rendering of a $400 million lab and research facility Drexel University and Gattuso Development Partners plan to build at 3201 Cuthbert St. in Philadelphia.

Enlarge

A rendering of a $400 million lab and research facility Drexel University and Gattuso Development Partners plan to build at 3201 Cuthbert St. in Philadelphia.

The building is 45% leased by Drexel and SmartLabs, an operator of life sciences labs. Drexel plans to occupy about 60,000 square feet, while SmartLabs will lease two floors totaling 117,000 square feet.

“We believe the project validates Philadelphia’s emergence as a global hub for life sciences research, and we are excited to begin construction,” said John Gattuso, the co-founder and president of Philadelphia-based Gattuso Development.

Ryan Ade, Brett Segal and Christopher Peck of JLL arranged the financing.

The project is another play in what amounts to an arms race for life sciences space and tenants in University City. Spark Therapeutics plans to build a $575 million, 500,000-square-foot gene therapy manufacturing plant on Drexel’s campus. One uCity Square, a $280 million, 400,000-square-foot life sciences building, was recently completed at 38th and Market streets. At 3151 Market St., a $307 million, 417,000-square-foot life sciences building is proposed as part of the Schuylkill Yards development.

Tmunity CEO Usman Azam departing to lead ‘stealth’ NYC biotech firm

 

By John George  –  Senior Reporter, Philadelphia Business Journal

Feb 7, 2022

The CEO of one of Philadelphia’s oldest cell therapy companies is departing to take a new job in the New York City area.

Usman “Oz” Azam, who has been CEO of Tmunity Therapeutics since 2016, will lead an unnamed biotechnology company currently operating in stealth mode.

In a posting on his LinkedIn page, Azam said, “After a decade immersed in cell therapies and immuno-oncology, I am now turning my attention to a new opportunity, and will be going back to where I started my life sciences career in neurosciences.”

Tmunity, a University of Pennsylvania spinout, is looking to apply CAR T-cell therapy, which has proved to be successful in treating liquid cancers, for the treatment of solid tumors.

Last summer, Tmunity suspended clinical testing of its lead cell therapy candidate targeting prostate cancer after two patients in the study died. Azam, in an interview with the Business Journal in June, said the company, which had grown to about 50 employees since its launch in 2015, laid off an undisclosed number of employees as a result of the setback.

Azam said on LinkedIn he is still a big believer in CAR T-cell therapy, noting Tmunity co-founder Dr. Carl June and his colleagues at Penn just published in Nature the 10-year landmark clinical outcomes study with the first CD19 CAR-T patients and programs.

“It’s just the beginning,” he stated. “I’m excited about the prospect of so many new cell- and gene-based therapies emerging in the next five to 10 years to tackle many solid and liquid tumors, and I hope we all continue to see the remarkable impact this makes on patients and families around the world.”

Azam could not be reached for comment Monday. Tmunity has engaged a search firm to identify his successor.

Tmunity, which is based in Philadelphia, has its own manufacturing operations in East Norriton. Tmunity’s founders include June and fellow Penn cell therapy pioneer Bruce Levine, who led the development of a CAR T-cell therapy now marketed by Novartis as Kymriah, a treatment for certain types of blood cancers.

In therapy using CAR-T cells, a patient’s T cells — part of their immune system — are removed and genetically modified in the laboratory. After they are re-injected into a patient, the T cells are better able to attack and destroy tumors. CAR is an acronym for chimeric antigen receptor. Chimeric antigen receptors are receptor proteins that have been engineered to give T cells their improved ability to target tumors.

Source: https://www.bizjournals.com/philadelphia/news/2022/02/07/tmunity-therapeutics-philadelphia-cell-azam-oz.html?utm_source=st&utm_medium=en&utm_campaign=BN&utm_content=pl&ana=e_pl_BN&j=30034971&senddate=2022-12-20

 

PIDC names U.S. Department of Treasury veteran, Philadelphia native as next president

 
By   –  Reporter, Philadelphia Business Journal

 

The Philadelphia Industrial Development Corp. has tapped U.S. Department of Treasury veteran Jodie Harris to be its next president.

Harris succeeds Anne Bovaird Nevins, who spent 15 years in the organization and took over as president in January 2020 before stepping down at the end of last year. Executive Vice President Sam Rhoads has been interim president.

Harris, a Philadelphia native who currently serves as director of the Community Development Financial Institutions Fund for the Department of Treasury, was picked after a regional and national search and will begin her tenure as president on June 1. She becomes the 12th head of PIDC and the first African-American woman to lead the organization.

PIDC is a public-private economic development corporation founded by the city and the Chamber of Commerce for Greater Philadelphia in 1958. It mainly uses industrial and commercial real estate projects to attract jobs, foster business opportunities and spur overall community growth. The organization has spurred over $18.5 billion in financing across its 65 years.

PIDC has its hand in development projects spanning the city, including master planning roles in expansive campuses like the Philadelphia Navy Yard and the Lower Schuylkill Biotech Campus in Southwest Philadelphia.

In a statement, Harris said that it is “a critical time for Philadelphia’s economy.”

“I’m especially excited for the opportunity to lead such an important and impactful organization in my hometown of Philadelphia,” Harris said. “As head of the CDFI Fund, I know first-hand what it takes to drive meaningful, sustainable, and equitable economic growth, especially in historically underserved communities.”

Harris is a graduate of the University of Maryland and received an MBA and master of public administration from New York University. In the Treasury Department, Harris’ most recent work aligns with PIDC’s economic development mission. At the Community Development Financial Institutions Fund, she oversaw a $331 million budget, mainly comprised of grant and administrative funding for various economic programs. Under Harris’ watch, the fund distributed over $3 billion in pandemic recovery funding, its highest level of appropriated grants ever.

Harris has been a part of the Treasury Department for 15 years, including as director of community and economic development policy.

In addition to government work, Harris has previously spent time in the private, academia and nonprofit sectors. In the beginning of her career, Harris worked at Meridian Bank and Accenture before turning to become a social and education policy researcher at New York University. She also spent two years as president of the Urban Business Assistance Corporation in New York.

Mayor Jim Kenney said that Philadelphia is “poised for long-term growth” and Harris will help drive it.

Source: https://www.bizjournals.com/philadelphia/news/2023/02/23/pidc-names-next-president-treasury.html 

$250M life sciences conversion planned for Philadelphia’s historic Quartermaster site

 
By   –  Reporter, Philadelphia Business Journal

Listen to this article     3 min

Real estate company SkyREM plans to spend $250 million converting the historic Quartermaster site in South Philadelphia to a life sciences campus with restaurants and a hotel.

The redevelopment would feature wet and dry lab space for research, development and bio-manufacturing.

The renamed Quartermaster Science + Technology Park is near the southwest corner of Oregon Avenue and South 20th Street in the city’s Girard Estates neighborhood. It’s east of the Quartermaster Plaza retail center, which sold last year for $100 million.

The 24-acre campus is planned to have six acres of green space, an Aldi grocery store opening by March and already is the headquarters for Indego, the bicycle share program in Philadelphia.

Six buildings totaling 1 million square feet of space would be used for research and development labs. There’s 500,000 square feet of vacant space available for life sciences and high technology companies with availabilities as small as 1,000 square feet up to 250,000 square feet contiguous. There’s also 150,000 square feet of retail space available.

The office park has 200,000 square feet already occupied by tenants. The Philadelphia Job Corps Center and Delaware Valley Intelligence Center are tenants at the site.

The campus was previously used by the military as a place to produce clothing, footwear and personal equipment during World War I and II. The clothing factory closed in 1994. The Philadelphia Quartermaster Depot was listed on the National Register of Historic Places in 2010.

“We had a vision to preserve the legacy of this built-to-last historic Philadelphia landmark and transform it to create a vibrant space where the best and brightest want to innovate, collaborate, and work,” SkyREM CEO and Founder Alex Dembitzer said in a statement.

SkyREM, a real estate investor and developer, has corporate offices in New York and Philadelphia. The company acquired the site in 2001.

Vered Nohi, SkyREM’s regional executive director of new business development, called the redevelopment “transformational” for Philadelphia.

 
 

Quartermaster would join a wave of new life sciences projects being developed in the surrounding area and across the region.

The site is near both interstates 76 and 95 and is about 2 miles north of the Philadelphia Navy Yard, which has undergone a similar transformation from a military hub to a major life sciences and mixed-use redevelopment project. The Philadelphia Industrial Development Corp. is also in the process of selecting a developer to create a massive cell and gene therapy manufacturing complex across two sites totaling about 40 acres on Southwest Philadelphia’s Lower Schuylkill riverfront.

At 34th Street and Grays Ferry Avenue, the University of Pennsylvania is teaming with Longfellow Real Estate Partners on proposed a $365 million, 455,000-square-foot life sciences and biomanufacturing building at Pennovation Works.

 

SkyREM is working with Maryland real estate firm Scheer Partners to lease the science and technology space. Philadelphia’s MPN Realty will handle leasing of the retail space. Architecture firm Fifteen is working on the project’s design.

Scheer Partners Senior Vice President Tim Conrey said the Quartermaster conversion will help companies solve for “speed to market” as demand for life science space in the region has been strong.

Brandywine pauses new spec office development, continues to bet big on life sciences

By   –  Reporter, Philadelphia Business Journal

 

Brandywine Realty Trust originally planned to redevelop a Radnor medical office into lab and office space, split 50-50 between the two uses.

After changes in demand for lab and office space, Brandywine (NYSE: BDN) recently completed the 168,000-square-foot, four-story building at 250 King of Prussia Road in Radnor fully for life sciences.

“The pipeline is now 100% life sciences, which, while requiring more capital, is also generating longer term leases at a higher return on cost,” Brandywine CEO Jerry Sweeney of the project said during the company’s fourth-quarter earnings call on Thursday.

At the same time, Brandywine is holding off on developing new office buildings unless it has a tenant lined up in advance.

The shift reflects how Philadelphia-based Brandywine continues to lean into — and bet big — on life sciences.

Brandywine is the city’s largest owner of trophy office buildings and has several major development projects in the works. The company is planning to eventually develop 3 million square feet of life sciences space. For now, 800,000 square feet of life sciences space is under development, including a 12-story, 417,000-square-foot life sciences building at 3151 Market St. and a 29-story building with 200,000 square feet of life sciences space at 3025 John F. Kennedy Blvd. Both are part of the multi-phase Schuylkill Yards project underway near 30th Street Station in University City.

Once its existing projects are completed, Brandywine would have 800,000 square feet of life sciences space, making up 8% of its portfolio.Sweeney said the company wants to grow that figure to 21%.

Brandywine is developing a 145,000-square-foot, build-to-suit office building at 155 King of Prussia Road in Radnor for Arkema, a France-based global supplier of specialty materials. The building will be Arkema’s North American headquarters. Construction began in January and is scheduled to be completed in late 2024.

Brandywine reported that since November it raised over $705 million through fourth-quarter asset sales, an unsecured bond transaction and a secured loan. The company has “complete availability” on its $600 million unsecured line of credit, Sweeney said.

Brandywine sold a 95% leased, 86,000-square-foot office building at 200 Barr Harbor Drive in West Conshohocken for $30.5 million. The company also sold its 50% ownership interest in the 1919 Market joint venture for $83.2 million to an undisclosed buyer. 1919 Market St. is a 29-story building with apartments, office and commercial space. Brandywine co-developed the property with LCOR and the California State Teacher’s Retirement System.

Brandywine declined to comment and LCOR could not be reached.

Brandywine’s core portfolio is 91% leased.

The project at 250 King of Prussia Road cost $103.7 million and was recently completed. The renovation included 12-foot high floor-to-ceiling glass on the second floor, a new roof, lobby, elevator core, common area with a skylight and an added structured parking deck.

Located in the Radnor Life Science Center, a new campus with nearly 1 million square feet of lab, research and office space, Sweeney said it’s a “magnet” for biotech companies. Avantor, a global manufacturer and distributor of life sciences products, is headquartered in the complex.

 

Sweeney said Brandywine is “very confident” demand will stay strong for life sciences in Radnor. The building at 250 King of Prussia Road is projected to be fully leased by early 2024.

“Larger users we’re talking to, they just tend to take a little bit more time than we would like as they go through technical requirements and space planning requirements,” Sweeney said.

While Brandywine is aiming to increase its life sciences footprint, the company is being selective about what it builds next. The company may steer away from developments other than life sciences. The Schuylkill Yards project, for example, features a significant life sciences portion in University City.

“Other than fully leased build-to-suit opportunities, our future development starts are on hold,” Sweeney said, “pending more leasing on the existing joint venture pipeline and more clarity on the cost of debt capital and cap rates.”

 

Brandywine said about 70% to 75%of suburban tenants have returned to offices while that number has been around 50% in Philadelphia. At this point, though, it hasn’t yet affected demand when leasing space. Some tenants, for example, have moved out of the city while others have moved in.

In the fourth quarter, Brandywine had $55.7 million funds from operations, or 32 cents per share. That’s down from $60.4 million, or 35 cents per share, in the fourth quarter of 2021. Brandywine generated $129 million in revenue in the fourth quarter, up slightly from $125.5 in the year-ago period.

Brandywine stock is up 6.4% since the start of the year to $6.70 per share on Monday afternoon.

Many of Brandywine’s properties are in desirable locations, which have seen demand remain strong despite challenges facing offices, on par with industry trends.

Brandywine’s 12-story, 417,000-square-foot building at 3151 Market St. is on budget for $308 million and on schedule to be completed in the second quarter of 2024. Sweeney said Brandywine anticipates entering a construction loan in the second half of 2023, which would help complete the project. The building, being developed along with a global institutional investor,would be used for life sciences, innovation and office space as part of the larger Schuylkill Yards development in University City.

The company’s 29-story building at 3025 John F. Kennedy Blvd. with 200,000 square feet of life sciences space and 326 luxury apartments, is also on budget, costing $287.3 million, and on time, eyeing completion in the third quarter of this year.

Source: https://www.bizjournals.com/philadelphia/news/2023/02/06/brandywine-realty-life-sciences-development.html

Read Full Post »

Bacterial multidrug resistance problem solved by a broad-spectrum synthetic antibiotic

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

There is an increasing demand for new antibiotics that effectively treat patients with refractory bacteremia, do not evoke bacterial resistance, and can be readily modified to address current and anticipated patient needs. Recently scientists described a promising compound of COE (conjugated oligo electrolytes) family, COE2-2hexyl, that exhibited broad-spectrum antibacterial activity. COE2-2hexyl effectively-treated mice infected with bacteria derived from sepsis patients with refractory bacteremia, including a CRE K. pneumoniae strain resistant to nearly all clinical antibiotics tested. Notably, this lead compound did not evoke drug resistance in several pathogens tested. COE2-2hexyl has specific effects on multiple membrane-associated functions (e.g., septation, motility, ATP synthesis, respiration, membrane permeability to small molecules) that may act together to abrogate bacterial cell viability and the evolution of drug-resistance. Impeding these bacterial properties may occur through alteration of vital protein–protein or protein-lipid membrane interfaces – a mechanism of action distinct from many membrane disrupting antimicrobials or detergents that destabilize membranes to induce bacterial cell lysis. The diversity and ease of COE design and chemical synthesis have the potential to establish a new standard for drug design and personalized antibiotic treatment.

Recent studies have shown that small molecules can preferentially target bacterial membranes due to significant differences in lipid composition, presence of a cell wall, and the absence of cholesterol. The inner membranes of Gram-negative bacteria are generally more negatively charged at their surface because they contain more anionic lipids such as cardiolipin and phosphatidylglycerol within their outer leaflet compared to mammalian membranes. In contrast, membranes of mammalian cells are largely composed of more-neutral phospholipids, sphingomyelins, as well as cholesterol, which affords membrane rigidity and ability to withstand mechanical stresses; and may stabilize the membrane against structural damage to membrane-disrupting agents such as COEs. Consistent with these studies, COE2-2hexyl was well tolerated in mice, suggesting that COEs are not intrinsically toxic in vivo, which is often a primary concern with membrane-targeting antibiotics. The COE refinement workflow potentially accelerates lead compound optimization by more rapid screening of novel compounds for the iterative directed-design process. It also reduces the time and cost of subsequent biophysical characterization, medicinal chemistry and bioassays, ultimately facilitating the discovery of novel compounds with improved pharmacological properties.

Additionally, COEs provide an approach to gain new insights into microbial physiology, including membrane structure/function and mechanism of drug action/resistance, while also generating a suite of tools that enable the modulation of bacterial and mammalian membranes for scientific or manufacturing uses. Notably, further COE safety and efficacy studies are required to be conducted on a larger scale to ensure adequate understanding of the clinical benefits and risks to assure clinical efficacy and toxicity before COEs can be added to the therapeutic armamentarium. Despite these limitations, the ease of molecular design, synthesis and modular nature of COEs offer many advantages over conventional antimicrobials, making synthesis simple, scalable and affordable. It enables the construction of a spectrum of compounds with the potential for development as a new versatile therapy for the emergence and rapid global spread of pathogens that are resistant to all, or nearly all, existing antimicrobial medicines.

References:

https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00026-9/fulltext#%20

https://pubmed.ncbi.nlm.nih.gov/36801104/

https://www.sciencedaily.com/releases/2023/02/230216161214.htm

https://www.nature.com/articles/s41586-021-04045-6

https://www.nature.com/articles/d43747-020-00804-y

Read Full Post »

2022 FDA Drug Approval List, 2022 Biological Approvals and Approved Cellular and Gene Therapy Products

 

 

Reporter: Aviva Lev-Ari, PhD, RN

SOURCE

Tal Bahar’s post on LinkedIn on 1/17/2023

Novel Drug Approvals for 2022

FDA’s Center for Drug Evaluation and Research (CDER)

New Molecular Entities (“NMEs”)

  • Some of these products have never been used in clinical practice. Below is a listing of new molecular entities and new therapeutic biological products that CDER approved in 2022. This listing does not contain vaccines, allergenic products, blood and blood products, plasma derivatives, cellular and gene therapy products, or other products that the Center for Biologics Evaluation and Research approved in 2022. 
  • Others are the same as, or related to, previously approved products, and they will compete with those products in the marketplace. See Drugs@FDA for information about all of CDER’s approved drugs and biological products. 

Certain drugs are classified as new molecular entities (“NMEs”) for purposes of FDA review. Many of these products contain active moieties that FDA had not previously approved, either as a single ingredient drug or as part of a combination product. These products frequently provide important new therapies for patients. Some drugs are characterized as NMEs for administrative purposes, but nonetheless contain active moieties that are closely related to active moieties in products that FDA has previously approved. FDA’s classification of a drug as an “NME” for review purposes is distinct from FDA’s determination of whether a drug product is a “new chemical entity” or “NCE” within the meaning of the Federal Food, Drug, and Cosmetic Act. 

INNOVATION   PREDICTABILITY   ACCESS FDA’s Center for Drug Evaluation and Research

January 2023

Table of Contents

 SOURCE

2022 Biological Approvals

The Center for Biologics Evaluation and Research (CBER) regulates products under a variety of regulatory authorities.  See the Development & Approval Process page for a description of what products are approved as Biologics License Applications (BLAs), Premarket Approvals (PMAs), New Drug Applications (NDAs) or 510Ks.

Biologics License Applications and Supplements

New BLAs (except those for blood banking), and BLA supplements that are expected to significantly enhance the public health (e.g., for new/expanded indications, new routes of administration, new dosage formulations and improved safety).

Other Applications Approved or Cleared by the Center for Biologics Evaluation and Research (CBER)

Medical devices involved in the collection, processing, testing, manufacture and administration of licensed blood, blood components and cellular products.

Key Resources

SOURCE

https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/2022-biological-approvals

 

Approved Cellular and Gene Therapy Products

Below is a list of licensed products from the Office of Tissues and Advanced Therapies (OTAT).


Approved Products


 

Resources For You


SOURCE

https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products

 

2022 forecast: Cell, gene therapy makers push past regulatory, payer hurdles to set up high hopes for next year

There are five FDA-approved CAR-T treatments for blood cancers and two gene therapies to treat rare diseases now on the market in the U.S. The late-stage pipeline could produce several more cancer CAR-Ts and gene therapies to treat a range of diseases.

RELATED: ASH: Bristol Myers’ Breyanzi, Gilead’s Yescarta lock horns in race to move CAR-T therapy to earlier lymphoma

One of the biggest races to watch in the cell therapy space will be that between Gilead Sciences’ Yescarta and Bristol Myers Squibb’s Breyanzi, both of which are gunning to move their CAR-Ts into earlier lines of treatment in large B-cell lymphoma (LBCL). At ASH, both companies rolled out impressive data from their trials in the second-line setting, but Gilead could have the upper hand by virtue of its three-year head start in the market, analysts said. Gilead expects to hear from the FDA on a label expansion in the second-line setting in April.

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The drug efflux pump MDR1 promotes intrinsic and acquired resistance to PROTACs in cancer cells

Reporter: Stephen J. Williams, PhD.
Below is one of the first reports  on the potential mechanisms of intrinsic and acquired resistance to PROTAC therapy in cancer cells.
Proteolysis-targeting chimeras (PROTACs) are a promising new class of drugs that selectively degrade cellular proteins of interest. PROTACs that target oncogene products are avidly being explored for cancer therapies, and several are currently in clinical trials. Drug resistance is a substantial challenge in clinical oncology, and resistance to PROTACs has been reported in several cancer cell models. Here, using proteomic analysis, we found intrinsic and acquired resistance mechanisms to PROTACs in cancer cell lines mediated by greater abundance or production of the drug efflux pump MDR1. PROTAC-resistant cells were resensitized to PROTACs by genetic ablation of ABCB1 (which encodes MDR1) or by coadministration of MDR1 inhibitors. In MDR1-overexpressing colorectal cancer cells, degraders targeting either the kinases MEK1/2 or the oncogenic mutant GTPase KRASG12C synergized with the dual epidermal growth factor receptor (EGFR/ErbB)/MDR1 inhibitor lapatinib. Moreover, compared with single-agent therapies, combining MEK1/2 degraders with lapatinib improved growth inhibition of MDR1-overexpressing KRAS-mutant colorectal cancer xenografts in mice. Together, our findings suggest that concurrent blockade of MDR1 will likely be required with PROTACs to achieve durable protein degradation and therapeutic response in cancer.

INTRODUCTION

Proteolysis-targeting chimeras (PROTACs) have emerged as a revolutionary new class of drugs that use cancer cells’ own protein destruction machinery to selectively degrade essential tumor drivers (1). PROTACs are small molecules with two functional ends, wherein one end binds to the protein of interest, whereas the other binds to an E3 ubiquitin ligase (23), bringing the ubiquitin ligase to the target protein, leading to its ubiquitination and subsequent degradation by the proteasome. PROTACs have enabled the development of drugs against previously “undruggable” targets and require neither catalytic activity nor high-affinity target binding to achieve target degradation (4). In addition, low doses of PROTACs can be highly effective at inducing degradation, which can reduce off-target toxicity associated with high dosing of traditional inhibitors (3). PROTACs have been developed for a variety of cancer targets, including oncogenic kinases (5), epigenetic proteins (6), and, recently, KRASG12C proteins (7). PROTACs targeting the androgen receptor or estrogen receptor are avidly being evaluated in clinical trials for prostate cancer (NCT03888612) or breast cancer (NCT04072952), respectively.
However, PROTACs may not escape the overwhelming challenge of drug resistance that befalls so many cancer therapies (8). Resistance to PROTACs in cultured cells has been shown to involve genomic alterations in their E3 ligase targets, such as decreased expression of Cereblon (CRBN), Von Hippel Lindau (VHL), or Cullin2 (CUL2) (911). Up-regulation of the drug efflux pump encoded by ABCB1—MDR1 (multidrug resistance 1), a member of the superfamily of adenosine 5′-triphosphate (ATP)–binding cassette (ABC) transporters—has been shown to convey drug resistance to many anticancer drugs, including chemotherapy agents, kinase inhibitors, and other targeted agents (12). Recently, PROTACs were shown to be substrates for MDR1 (1013), suggesting that drug efflux represents a potential limitation for degrader therapies. Here, using degraders (PROTACs) against bromodomain and extraterminal (BET) bromodomain (BBD) proteins and cyclin-dependent kinase 9 (CDK9) as a proof of concept, we applied proteomics to define acquired resistance mechanisms to PROTAC therapies in cancer cells after chronic exposure. Our study reveals a role for the drug efflux pump MDR1 in both acquired and intrinsic resistance to protein degraders in cancer cells and supports combination therapies involving PROTACs and MDR1 inhibitors to achieve durable protein degradation and therapeutic responses.

Fig. 1. Proteomic characterization of degrader-resistant cancer cell lines.
(A) Workflow for identifying protein targets up-regulated in degrader-resistant cancer cells. Single-run proteome analysis was performed, and changes in protein levels among parent and resistant cells were determined by LFQ. m/z, mass/charge ratio. (B and C) Cell viability assessed by CellTiter-Glo in parental and dBET6- or Thal SNS 032–resistant A1847 cells treated with increasing doses of dBET6 (B) or Thal SNS 032 (C) for 5 days. Data were analyzed as % of DMSO control, presented as means ± SD of three independent assays. Growth inhibitory 50% (GI50) values were determined using Prism software. (D to G) Immunoblotting for degrader targets and downstream signaling in parental A1847 cells and their derivative dBET6-R or Thal-R cells treated with increasing doses of dBET6 or Thal SNS 032 for 4 hours. The dBET6-R and Thal-R cells were continuously cultured in 500 nM PROTAC. Blots are representative, and densitometric analyses are means ± SD from three blots, each normalized to the loading control, GAPDH. DC50 values, quantitating either (E) the dose of dBET6 that reduces BRD2, BRD3, or BRD4 or (G) the dose of Thal SNS 032 that reduces CDK9 protein levels 50% of the DMSO control treatment, were determined with Prism software. Pol II, polymerase II. (H to K) Volcano plot of proteins with increased or reduced abundance in dBET6-R (H) or Thal-R (I) A1847 cells relative to parental cells. Differences in protein log2 LFQ intensities among degrader-resistant and parental cells were determined by paired t test permutation-based adjusted P values at FDR of <0.05 using Perseus software. The top 10 up-regulated proteins in each are shown in (J) and (K), respectively. FC, fold change. (L and M) ABCB1 log2 LFQ values in dBET6-R cells from (H) and Thal-R cells from (I) compared with those in parental A1847 cells. Data are presented as means ± SD from three independent assays. By paired t test permutation-based adjusted P values at FDR of <0.05 using Perseus software, ***P ≤ 0.001. (N) Cell viability assessed by CellTiter-Glo in parental and MZ1-resistant SUM159 cells treated with increasing doses of MZ1 for 5 days. Data were analyzed as % of DMSO control, presented as means of three independent assays. GI50 values were determined using Prism software. (O and P) Immunoblotting for degrader targets and downstream signaling in parental or MZ1-R SUM159 cells treated with increasing doses of MZ1 for 24 hours. The MZ1-R cells were continuously cultured in 500 nM MZ1. Blots are representative, and densitometric analyses are means ± SD from three blots, each normalized to the loading control, GAPDH. DC50 values were determined in Prism software. (Q and R) Top 10 up-regulated proteins (Q) and ABCB1 log2 LFQ values (R) in MZ1-R cells relative to parental SUM159 cells

Fig. 2. Chronic exposure to degraders induces MDR1 expression and drug efflux activity.
(A) ABCB1 mRNA levels in parental and degrader-resistant cell lines as determined by qRT-PCR. Data are means ± SD of three independent experiments. ***P ≤ 0.001 by Student’s t test. (B) Immunoblot analysis of MDR1 protein levels in parental and degrader-resistant cell lines. Blots are representative of three independent experiments. (C to E) Immunofluorescence (“IF”) microscopy of MDR1 protein levels in A1847 dBET6-R (C), SUM159 MZ1-R (D), and Thal-R A1847 cells (E) relative to parental cells. Nuclear staining by DAPI. Images are representative of three independent experiments. Scale bars, 100 μm. (F) Drug efflux activity in A1847 dBET6-R, SUM159 MZ1-R, and Thal-R A1847 cells relative to parental cells (Par.) using rhodamine 123 efflux assays. Bars are means ± SD of three independent experiments. ***P ≤ 0.001 by Student’s t test. (G) Intracellular dBET6 levels in parental or dBET-R A1847 cells transfected with a CRBN sensor and treated with increasing concentrations of dBET6. Intracellular dBET6 levels measured using the CRBN NanoBRET target engagement assay. Data were analyzed as % of DMSO control, presented as means ± SD of three independent assays. *P ≤ 0.05, **P ≤ 0.01, and ***P ≤ 0.001 by Student’s t test. (H and I) FISH analysis of representative drug-sensitive parental and drug-resistant A1847 (H) and SUM159 (I) cells using ABCB1 and control XCE 7 centromere probes. Images of interphase nuclei were captured with a Metasystems Metafer microscope workstation, and the raw images were extracted and processed to depict ABCB1 signals in magenta, centromere 7 signals in cyan, and DAPI-stained nuclei in blue. (J and K) CpG methylation status of the ABCB1 downstream promoter (coordinates: chr7.87,600,166-87,601,336) by bisulfite amplicon sequencing in parent and degrader-resistant A1847 (J) and SUM159 (K) cells. Images depict the averaged percentage of methylation for each region of the promoter, where methylation status is depicted by color as follows: red, methylated; blue, unmethylated. Schematic of the ABCB1 gene with the location of individual CpG sites is shown. Graphs are representative of three independent experiments. (L and M) Immunoblot analysis of MDR1 protein levels after short-term exposure [for hours (h) or days (d) as indicated] to BET protein degraders dBET6 or MZ1 (100 nM) in A1847 (L) and SUM159 (M) cells, respectively. Blots are representative of three independent experiments. (N to P) Immunoblot analysis of MDR1 protein levels in A1847 and SUM159 cells after long-term exposure (7 to 30 days) to BET protein degraders dBET6 (N), Thal SNS 032 (O), or MZ1 (P), each at 500 nM. Blots are representative of three independent experiments. (Q and R) Immunoblot analysis of MDR1 protein levels in degrader-resistant A1847 (Q) and SUM159 (R) cells after PROTAC removal for 2 or 7 days. Blots are representative of three independent experiments.

 

Fig. 3. Blockade of MDR1 activity resensitizes degrader-resistant cells to PROTACs.
(A and B) Cell viability by CellTiter-Glo assay in parental and degrader-resistant A1847 (A) and SUM159 (B) cells transfected with control siRNA or siRNAs targeting ABCB1 and cultured for 120 hours. Data were analyzed as % of control, presented as means ± SD of three independent assays. ***P ≤ 0.001 by Student’s t test. (C and D) Immunoblot analysis of degrader targets after ABCB1 knockdown in parental and degrader-resistant A1847 (C) and SUM159 (D) cells. Blots are representative, and densitometric analyses using ImageJ are means ± SD of three blots, each normalized to the loading control, GAPDH. (E) Drug efflux activity, using the rhodamine 123 efflux assay, in degrader-resistant cells after MDR1 inhibition by tariquidar (0.1 μM). Data are means ± SD of three independent experiments. ***P ≤ 0.001 by Student’s t test. (F to H) Cell viability by CellTiter-Glo assay in parental and dBET6-R (F) or Thal-R (G) A1847 cells or MZ1-R SUM159 cells (H) treated with increasing concentrations of tariquidar. Data are % of DMSO control, presented as means ± SD of three independent assays. GI50 value determined with Prism software. (I to K) Immunoblot analysis of degrader targets after MDR1 inhibition (tariquidar, 0.1 μM for 24 hours) in parental and degrader-resistant A1847 cells (I and J) and SUM159 cells (K). Blots are representative, and densitometric analyses are means ± SD from three blots, each normalized to the loading control, GAPDH. (L and M) A 14-day colony formation assessed by crystal violet staining of (L) A1847 cells or (M) SUM159 cells treated with degrader (0.1 μM; dBET6 or MZ1, respectively) and MDR1 inhibitor tariquidar (0.1 μM). Images are representative of three biological replicates. (N) Immunoblotting for MDR1 in SUM159 cells stably expressing FLAG-MDR1 after selection with hygromycin. (O) Long-term 14-day colony formation assay of SUM159 cells expressing FLAG-MDR1 that were treated with DMSO, MZ1 (0.1 μM), or MZ1 and tariquidar (0.1 μM) for 14 days, assessed by crystal violet staining. Representative images of three biological replicates are shown. (P and Q) RT-PCR (P) and immunoblot (Q) analysis of ABCB1 mRNA and MDR1 protein levels, respectively, in parental or MZ1-R HCT116, OVCAR3, and MOLT4 cells.

 

Fig. 4. Overexpression of MDR1 conveys intrinsic resistance to degrader therapies in cancer cells.
(A) Frequency of ABCB1 mRNA overexpression in a panel of cancer cell lines, obtained from cBioPortal for Cancer Genomics using Z-score values of >1.2 for ABCB1 mRNA levels (30). (B) Immunoblot for MDR1 protein levels in a panel of 10 cancer cell lines. Blots are representative of three independent experiments. (C) Cell viability by CellTiter-Glo assay in cancer cell lines expressing high or low MDR1 protein levels and treated with Thal SNS 032 for 5 days. Data were analyzed as % of DMSO control, presented as means ± SD of three independent assays. GI50 values were determined with Prism software. (D to F) Immunoblot analysis of CDK9 in MDR1-low (D) or MDR1-high (E) cell lines after Thal SNS 032 treatment for 4 hours. Blots are representative, and densitometric analyses using ImageJ are means ± SD from three blots, each normalized to the loading control, GAPDH. DC50 value determined with Prism. (G and H) Immunoblotting of control and MDR1-knockdown DLD-1 cells treated for 4 hours with increasing concentrations of Thal SNS 032 [indicated in (H)]. Blots are representative, and densitometric analysis data are means ± SD from three blots, each normalized to the loading control, GAPDH. DC50 value determined with Prism. (I) Drug efflux activity using rhodamine 123 efflux assays in DLD-1 cells treated with DMSO or 0.1 μM tariquidar. Data are means ± SD of three independent experiments. ***P ≤ 0.001 by Student’s t test. (J) Intracellular Thal SNS 032 levels, using the CRBN NanoBRET target engagement assay, in MDR1-overexpressing DLD-1 cells treated with DMSO or 0.1 μM tariquidar and increasing doses of Thal SNS 032. Data are % of DMSO control, presented as means ± SD of three independent assays. **P ≤ 0.01 and ***P ≤ 0.001 by Student’s t test. (K to N) Immunoblotting in DLD-1 cells treated with increasing doses of Thal SNS 032 (K and L) or dBET6 (M and N) alone or with tariquidar (0.1 μM) for 4 hours. Blots are representative, and densitometric analyses are means ± SD from three blots, each normalized to the loading control, GAPDH. DC50 value of Thal SNS 032 for CDK9 reduction (L) or of dBET6 for BRD4 reduction (N) determined with Prism. (O to T) Bliss synergy scores based on cell viability by CellTiter-Glo assay, colony formation, and immunoblotting in DLD-1 cells treated with the indicated doses of Thal SNS 032 (O to Q) or dBET6 (R to T) alone or with tariquidar. Cells were treated for 14 days for colony formation assays and 24 hours for immunoblotting.

 

Fig. 5. Repurposing dual kinase/MDR1 inhibitors to overcome degrader resistance in cancer cells.
(A and B) Drug efflux activity by rhodamine 123 efflux assays in degrader-resistant [dBET-R (A) or Thal-R (B)] A1847 cells after treatment with tariquidar, RAD001, or lapatinib (each 2 μM). Data are means ± SD of three independent experiments. *P ≤ 0.05 by Student’s t test. (C and D) CellTiter-Glo assay for the cell viability of parental, dBET6-R, or Thal-R A1847 cells treated with increasing concentrations of RAD001 (C) or lapatinib (D). Data were analyzed as % of DMSO control, presented as means ± SD of three independent assays. GI50 values were determined with Prism software. (E to I) Immunoblot analysis of degrader targets in parental (E), dBET6-R (F and G), and Thal-R (H and I) A1847 cells treated with increasing concentrations of RAD001 or lapatinib for 4 hours. Blots are representative, and densitometric analyses are means ± SD from three blots, each normalized to the loading control, GAPDH. DC50 value of dBET6 for BRD4 reduction (G) or of Thal SNS 032 for CDK9 reduction (I) determined with Prism. (J) Immunoblotting for cleaved PARP in dBET6-R or Thal-R A1847 cells treated with RAD001, lapatinib, or tariquidar (each 2 μM) for 24 hours. Blots are representative of three independent blots. (K to N) Immunoblotting for BRD4 in DLD-1 cells treated with increasing doses of dBET6 alone or in combination with either RAD001 or lapatinib [each 2 μM (K and L)] or KU-0063794 or afatinib [each 2 μM (M and N)] for 4 hours. Blots are representative of three independent experiments and, in (L), are means ± SD from three blots, each normalized to the loading control, GAPDH. DC50 value for BRD4 reduction (L) determined in Prism. (O) Colony formation by DLD-1 cells treated with DMSO, dBET6 (0.1 μM), lapatinib (2 μM), afatinib (2 μM), RAD001 (2 μM), KU-0063794 (2 μM), or the combination of inhibitor and dBET6 for 14 days. Images representative of three independent assays. (P and Q) Immunoblotting for CDK9 in DLD-1 cells treated with increasing doses of Thal SNS 032 and/or RAD001 (2 μM) or lapatinib (2 μM) for 4 hours. Blots are representative, and densitometric analyses are means ± SD from three blots, each normalized to the loading control, GAPDH. DC50 value for CDK9 reduction determined with Prism (Q). (R) Colony formation in DLD-1 cells treated with DMSO, Thal SNS 032 (0.5 μM), lapatinib (2 μM), and/or RAD001 (2 μM) as indicated for 14 days.

 

Fig. 6. Combining MEK1/2 degraders with lapatinib synergistically kills MDR1-overexpressing KRAS-mutant CRC cells and tumors.
(A and B) ABCB1 expression in KRAS-mutant CRC cell lines from cBioPortal (30) (A) and MDR1 abundance in select KRAS-mutant CRC cell lines (B). (C) Cell viability assessed by CellTiter-Glo in CRC cells treated with increasing doses of MS432 for 5 days, analyzed as % of DMSO control. GI50 value determined with Prism software. (D) Colony formation by CRC cells 14 days after treatment with 1 μM MS432. (E) MEK1/2 protein levels assessed by immunoblot in CRC lines SKCO1 (low MDR1) or LS513 (high MDR1) treated with increasing doses of MS432 for 4 hours. (F) Rhodamine 123 efflux in LS513 cells treated with DMSO, 2 μM tariquidar, or 2 μM lapatinib. (G and H) Immunoblotting analysis in LS513 cells treated with increasing doses of MS432 alone or in combination with tariquidar (0.1 μM) or lapatinib (5 μM) for 24 hours. DC50 value for MEK1 levels determined with Prism. (I) Immunoblotting in LS513 cells treated with DMSO, PD0325901 (0.01 μM), lapatinib (5 μM), or the combination for 48 hours. (J and K) Immunoblotting in LS513 cells treated either with DMSO, MS432 (1 μM), tariquidar (0.1 μM) (J), or lapatinib (5 μM) (K), alone or in combination. (L) Bliss synergy scores determined from cell viability assays (CellTiter-Glo) in LS513 cells treated with increasing concentrations of MS432, lapatinib, or the combination. (M and N) Colony formation by LS513 cells (M) and others (N) treated with DMSO, lapatinib (2 μM), MS432 (1 μM), or the combination for 14 days. (O and P) Immunoblotting in LS513 cells treated with increasing doses of MS934 alone (O) or combined with lapatinib (5 μM) (P) for 24 hours. (Q and R) Tumor volume of LS513 xenografts (Q) and the body weights of the tumor-bearing nude mice (R) treated with vehicle, MS934 (50 mg/kg), lapatinib (100 mg/kg), or the combination. n = 5 mice per treatment group. In (A) to (R), blots and images are representative of three independent experiments, and quantified data are means ± SD [SEM in (Q) and (R)] of three independent experiments; ***P ≤ 0.001 by Student’s t test.

 

Fig. 7. Lapatinib treatment improves KRASG12C degrader therapies in MDR1-overexpressing CRC cell lines.
(A and B) Colony formation by SW1463 (A) or SW837 (B) cells treated with DMSO, LC-2 (1 μM), or MRTX849 (1 μM) for 14 days. Images representative of three independent assays. (C to E) Immunoblotting in SW1463 cells (C and D) and SW837 cells (E) treated with DMSO, LC-2 (1 μM), tariquidar (0.1 μM) (C), or lapatinib (5 μM) (D and E) alone or in combination for 48 hours. Blots are representative of three independent experiments. (F and G) Bliss synergy scores based on CellTiter-Glo assay for the cell viability of SW1463 (F) or SW837 (G) cells treated with increasing concentrations of LC-2, lapatinib, or the combination. Data are means of three experiments ± SD. (H and I) Colony formation of SW1463 (H) or SW837 (I) cells treated as indicated (−, DMSO; LC-2, 1 μM; lapatinib, 2 μM; tariquidar, 0.1 μM) for 14 days. Images representative of three independent assays. (J) Rationale for combining lapatinib with MEK1/2 or KRASG12C degraders in MDR1-overexpressing CRC cell lines. Simultaneous blockade of MDR1 and ErbB receptor signaling overcomes degrader resistance and ErbB receptor kinome reprogramming, resulting in sustained inhibition of KRAS effector signaling.

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Other articles in this Open Access Scientific Journal on PROTAC therapy in cancer include

Accelerating PROTAC drug discovery: Establishing a relationship between ubiquitination and target protein degradation

The Vibrant Philly Biotech Scene: Proteovant Therapeutics Using Artificial Intelligence and Machine Learning to Develop PROTACs

The Map of human proteins drawn by artificial intelligence and PROTAC (proteolysis targeting chimeras) Technology for Drug Discovery

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