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First AI-designed drugs fall short in the clinic, following years of hype

The first AI-designed drugs have ended with disappointment.
Over the last year-plus, the first handful of molecules created by artificial intelligence…



The first AI-designed drugs have ended with disappointment.

Over the last year-plus, the first handful of molecules created by artificial intelligence have failed trials or been deprioritized. The AI companies behind these drugs brought them into the clinic full of fanfare about a new age of drug discovery — and have quietly shelved them after learning old lessons about how hard pharmaceutical R&D can be.

Earlier this month, UK-based Exscientia slipped into a pipeline update that a Phase I/II study of its cancer drug candidate EXS-21546 was winding down. That cut followed a decision last year by its partner Sumitomo Pharma to abandon another of its AI-designed drugs. In April, a test of BenevolentAI’s dermatitis drug fell short as well. And Recursion Pharmaceuticals — the third of AI’s early generation — hasn’t recorded a trial failure but has had a handful of clinical setbacks that don’t necessarily bode well.

Patrick Malone

There’s no shortage of AI naysayers, and the 0-for-3 start suggests that AI hype has set unrealistic expectations. Clinical wins are rarities in biotech, where an estimated 5% or 10% of drugs that head into human testing actually get approved.

“If you take the hype and PR at face value over the last 10 years, you would think it goes from 5% to 90%,” Patrick Malone, a principal at KdT Ventures, said of AI. “But if you know how these models work, it goes from 5% to maybe 6% or 7%.”

These three companies have been at this for roughly a decade, combining to rack up an accumulated deficit of over $1.5 billion.

Ivan Griffin

The reality check of the clinic, paired with a dour biotech market, has beaten up these first-generation biotechs that went public in 2021 or 2022. Their stock prices are all down at least 75%, underperforming the biotech market, even as new AI startups have continued to raise substantial sums of money. Generate:Biomedicines, Inceptive, Iambic and Genesis, for instance, have combined to raise $673 million over the past few months.

Executives at these first-generation companies say it’s too early for a verdict on whether or not AI boosts the odds of success, particularly given the vast likelihood that any drug candidate — AI-developed or not — will fail.

“The things that are easiest to show — speed and cost, particularly on the preclinical — have been done,” Ivan Griffin, BenevolentAI’s co-founder and chief operating officer, said in an interview with Endpoints News. Increasing the probability of success “will inevitably take the longest to prove out.”

Milestone moments to quiet cancellations

Back in the final days of January 2020, as Covid-19 was emerging as a pandemic threat, Exscientia CEO Andrew Hopkins hailed a “key milestone in drug discovery.”

His biotech announced the first AI-designed drug had entered the clinic. Its partner Sumitomo led the Phase I study in obsessive-compulsive disorder, with the Financial Times calling the trial’s start a “critical milestone for the role of machine learning in medicine.”

About two years later, in January 2022, Sumitomo disclosed they had abandoned the drug, which failed to meet the study’s criteria. In an interview, Hopkins said Exscientia’s job was to just design the molecule, with Sumitomo making the clinical decisions.

Exscientia had more control over the next drug, a cancer treatment called EXS-21546, which it brought into the clinic in December 2020. Earlier this month, the biotech said it was discontinuing an ongoing Phase I/II study with modeling suggesting “it will be challenging for ‘546 to reach a suitable therapeutic index.”

Andrew Hopkins

Hopkins said that the trial didn’t fail, as the biotech doesn’t have full results back.

“It wasn’t a clinical data decision,” he said. “It was a strategic decision” to prioritize two other cancer drugs that the company believes have better chances.

“We don’t want to be one of those companies that keeps pushing a program forward because it’s the only thing they have,” Hopkins said.

Clinical failure is less contestable for BenevolentAI, a fellow UK-based AI enthusiast whose lead drug was unable to beat a placebo in a Phase IIa atopic dermatitis study, the biotech announced earlier this year. That readout led to the drug’s end, a stock plunge, and sizable layoffs.

Recursion stands apart as the only one of the three to maintain a valuation above $1 billion today. (Exscientia is worth about $650 million, while BenevolentAI is valued at $117 million.)  The biotech has had several positive Phase I readouts centered on safety and tolerability, such as a C. diff drug recently clearing a healthy volunteer study of 42 people. The company used AI to identify existing compounds rather than design new drugs for its early pipeline.

Dylan Reid

“The market has never known what to make of these companies,” said Dylan Reid, a partner at Zetta Venture Partners. “They’ve been way too excited and way too down. At one point, they value the platform at X billions of dollars, and today, it’s probably a drag on valuation.”

While Recursion hasn’t had a clinical failure, its development plans have had hiccups. It quietly dropped a rare disease drug last year, citing “noise in the potency” and delays in getting a trial going. Earlier this month, the Salt Lake City-based biotech slimmed down an ongoing Phase II study for another of its drugs, dropping a placebo arm and cutting expected enrollment to 37 people. A spokesperson said the changes will help get to data and Phase III faster.

If a decade sounds too soon to judge these biotechs, consider Recursion’s leaders set that timeline themselves, publicly declaring the goal of discovering 100 clinical-stage drug candidates in its first 10 years. Roughly 10 years on, Recursion’s pipeline has four clinical-stage molecules.

Recursion expects two Phase II readouts in the second half of 2024. All three biotechs have ongoing partnerships with drugmaking giants like Merck, Bristol Myers Squibb, and Roche’s Genentech.

The AI clinical pipeline is full of other players as well, such as Verge Genomics’ ALS drug, BPGbio’s brain cancer treatment, Insilico Medicine’s idiopathic pulmonary fibrosis drug, Generate:Biomedicines’ Covid-19 antibody, and Auransa’s liver cancer therapy.

Strategies evolve as more players emerge

AI backers say successful programs like Moderna’s Covid-19 vaccine or Nimbus Therapeutics’ TYK2 inhibitor used AI to a degree. But those drugmakers don’t brand those medicines as AI-designed, while Exscientia, BenevolentAI, and Recursion market their approach as AI-driven or AI-enabled.

A decade in, leaders of the first-generation companies say they are still learning.

BenevolentAI, for instance, says its failed atopic dermatitis drug candidate didn’t use the company’s target identification approach, which is behind its ulcerative colitis drug that entered the clinic earlier this year.

Exscientia has incorporated more human tissue samples in its research process and hired experienced clinical hands like Michael Krams, Hopkins said.

“We’ve also now realized if we want to change the probability of success in the clinic, it’s not just better molecules,” Hopkins said. “We also need better translational models.”

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Delivering aid during war is tricky − here’s what to know about what Gaza relief operations may face

The politics of delivering aid in war zones are messy, the ethics fraught and the logistics daunting. But getting everything right is essential − and…




Palestinians on the outskirts of Gaza City walk by buildings destroyed by Israeli bombardment on Oct. 20, 2023. AP Photo/Ali Mahmoud

The 2.2 million people who live in Gaza are facing economic isolation and experiencing incessant bombardment. Their supplies of essential resources, including food and water, are quickly dwindling.

In response, U.S. President Joe Biden has pledged US$100 million in humanitarian assistance for the citizens of Gaza.

As a scholar of peace and conflict economics who served as a World Bank consultant during the 2014 war between Hamas and Israel, I believe that Biden’s promise raises fundamental questions regarding the delivery of humanitarian aid in a war zone. Political constraints, ethical quandaries and the need to protect the security of aid workers and local communities always make it a logistical nightmare.

In this specific predicament, U.S. officials have to choose a strategy to deliver the aid without the perception of benefiting Hamas, a group the U.S. and Israel both classify as a terrorist organization.


When aiding people in war zones, you can’t just send money, a development strategy called “cash transfers” that has become increasingly popular due to its efficiency. Sending money can boost the supply of locally produced goods and services and help people on the ground pay for what they need most. But injecting cash into an economy so completely cut off from the world would only stoke inflation.

So the aid must consist of goods that have to be brought into Gaza, and services provided by people working as part of an aid mission. Humanitarian aid can include food and water; health, sanitation and hygiene supplies and services; and tents and other materials for shelter and settlement.

Due to the closure of the border with Israel, aid can arrive in Gaza only via the Rafah crossing on the Egyptian border.

The U.S. Agency for International Development, or USAID, will likely turn to its longtime partner on the ground, the United Nations Relief and Works Agency, or UNRWA, to serve as supply depots and distribute goods. That agency, originally founded in 1949 as a temporary measure until a two-state solution could be found, serves in effect as a parallel yet unelected government for Palestinian refugees.

USAID will likely want to tap into UNRWA’s network of 284 schools – many of which are now transformed into humanitarian shelters housing two-thirds of the estimated 1 million people displaced by Israeli airstrikes – and 22 hospitals to expedite distribution.

Map of Gaza and its neighbors
Gaza is a self-governing Palestinian territory. The narrow piece of land is located on the coast of the Mediterranean Sea, bordered by Israel and Egypt. PeterHermesFurian/iStock via Getty Images Plus


Prior to the Trump administration, the U.S. was typically the largest single provider of aid to the West Bank and Gaza. USAID administers the lion’s share of it.

Since Biden took office, total yearly U.S. assistance for the Palestinian territories has totaled around $150 million, restored from just $8 million in 2020 under the Trump administration. During the Obama administration, however, the U.S. was providing more aid to the territories than it is now, with $1 billion disbursed in the 2013 fiscal year.

But the White House needs Congress to approve this assistance – a process that requires the House of Representatives to elect a new speaker and then for lawmakers to approve aid to Gaza once that happens.


The United Nations Relief and Works Agency is a U.N. organization. It’s not run by Hamas, unlike, for instance, the Gaza Ministry of Health. However, Hamas has frequently undermined UNRWA’s efforts and diverted international aid for military purposes.

Hamas has repeatedly used UNRWA schools as rocket depots. They have repeatedly tunneled beneath UNRWA schools. They have dismantled European Union-funded water pipes to use as rocket fuselages. And even since the most recent violence broke out, the UNRWA has accused Hamas of stealing fuel and food from its Gaza premises.

Humanitarian aid professionals regularly have to contend with these trade-offs when deciding to what extent they can work with governments and local authorities that commit violent acts. They need to do so in exchange for the access required to help civilians under their control.

Similarly, Biden has had to make concessions to Israel while brokering for the freedom to send humanitarian aid to Gaza. For example, he has assured Israel that if any of the aid is diverted by Hamas, the operation will cease.

This promise may have been politically necessary. But if Biden already believes Hamas to be uncaring about civilian welfare, he may not expect the group to refrain from taking what they can.

Security best practices

What can be done to protect the security of humanitarian aid operations that take place in the midst of dangerous conflicts?

Under International Humanitarian Law, local authorities have the primary responsibility for ensuring the delivery of aid – even when they aren’t carrying out that task. To increase the chances that the local authorities will not attack them, aid groups can give “humanitarian notification” and voluntarily alert the local government as to where they will be operating.

Hamas has repeatedly flouted international norms and laws. So the question of if and how the aid convoy will be protected looms large.

Under the current agreement between the U.S., Israel and Egypt, the convoy will raise the U.N. flag. International inspectors will make sure no weapons are on board the vehicles before crossing over from Arish, Egypt, to Rafah, a city located on the Gaza Strip’s border with Egypt.

The aid convoy will likely cross without militarized security. This puts it at some danger of diversion once inside Gaza. But whether the aid convoy is attacked, seized or left alone, the Biden administration will have demonstrated its willingness to attempt a humanitarian relief operation. In this sense, a relatively small first convoy bearing water, medical supplies and food, among other items, serves as a test balloon for a sustained operation to follow soon after.

If the U.S. were to provide the humanitarian convoy a military escort, by contrast, Hamas could see its presence as a provocation. Washington’s support for Israel is so strong that the U.S. could potentially be judged as a party in the conflict between Israel and Hamas.

In that case, the presence of U.S. armed forces might provoke attacks on Gaza-bound aid convoys by Hamas and Islamic jihad fighters that otherwise would not have occurred. Combined with the mobilization of two U.S. Navy carrier groups in the eastern Mediterranean Sea, I’d be concerned that such a move might also stoke regional anger. It would undermine the Biden administration’s attempts to cool the situation.

On U.N.-approved missions, aid delivery may be secured by third-party peacekeepers – meaning, in this case, personnel who are neither Israeli nor Palestinian – with the U.N. Security Council’s blessing. In this case, tragically, it’s unlikely that such a resolution could conceivably pass such a vote, much less quickly enough to make a difference.

Topher L. McDougal does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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Diagnosis and management of postoperative wound infections in the head and neck region

“The majority of wound infections often manifest themselves immediately postoperatively, so close followup should take place […]” Credit: 2023 Barbarewicz…



“The majority of wound infections often manifest themselves immediately postoperatively, so close followup should take place […]”

Credit: 2023 Barbarewicz et al.

“The majority of wound infections often manifest themselves immediately postoperatively, so close followup should take place […]”

BUFFALO, NY- October 20, 2023 – A new research perspective was published in Oncoscience (Volume 10) on October 4, 2023, entitled, “Diagnosis and management of postoperative wound infections in the head and neck region.”

In everyday clinical practice at a department for oral and maxillofacial surgery, a large number of surgical procedures in the head and neck region take place under both outpatient and inpatient conditions. The basis of every surgical intervention is the patient’s consent to the respective procedure. Particular attention is drawn to the general and operation-specific risks. 

Particularly in the case of soft tissue procedures in the facial region, bleeding, secondary bleeding, scarring and infection of the surgical area are among the most common complications/risks, depending on the respective procedure. In their new perspective, researchers Filip Barbarewicz, Kai-Olaf Henkel and Florian Dudde from Army Hospital Hamburg in Germany discuss the diagnosis and management of postoperative infections in the head and neck region.

“In order to minimize the wound infections/surgical site infections, aseptic operating conditions with maximum sterility are required.”

Furthermore, depending on the extent of the surgical procedure and the patient‘s previous illnesses, peri- and/or postoperative antibiotics should be considered in order to avoid postoperative surgical site infection. Abscesses, cellulitis, phlegmone and (depending on the location of the procedure) empyema are among the most common postoperative infections in the respective surgical area. The main pathogens of these infections are staphylococci, although mixed (germ) patterns are also possible. 

“Risk factors for the development of a postoperative surgical site infection include, in particular, increased age, smoking, multiple comorbidities and/or systemic diseases (e.g., diabetes mellitus type II) as well as congenital and/ or acquired immune deficiency [10, 11].”


Continue reading the paper: DOI: 

Correspondence to: Florian Dudde


Keywords: surgical site infection, head and neck surgery


About Oncoscience

Oncoscience is a peer-reviewed, open-access, traditional journal covering the rapidly growing field of cancer research, especially emergent topics not currently covered by other journals. This journal has a special mission: Freeing oncology from publication cost. It is free for the readers and the authors.

To learn more about Oncoscience, visit and connect with us on social media:

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G77 Nations, China, Push Back On U.S. “Loss And Damage” Climate Fund In Days Leading Up To UN Summit

G77 Nations, China, Push Back On U.S. "Loss And Damage" Climate Fund In Days Leading Up To UN Summit

As was the case in primary school with…



G77 Nations, China, Push Back On U.S. "Loss And Damage" Climate Fund In Days Leading Up To UN Summit

As was the case in primary school with bringing in presents, make sure you bring enough for the rest of the class, otherwise people get ornery...

This age old rule looks like it could be rearing its head in the days leading up to the UN COP 28 climate summit, set to take place in the United Arab Emirates in about six weeks. 

At the prior UN COP 27, which took place in Egypt last year, the U.S. pushed an idea for a new World Bank "loss and damage" climate slush fund to help poor countries with climate change. But the G77 nations plus China, including many developing countries, are pushing back on the idea, according to a new report from the Financial Times

The goal was to arrange how the fund would operate and where the money would come from for the "particularly vulnerable" nations who would have access to it prior to the upcoming summit in UAE.

But as FT notes, Pedro Luis Pedroso Cuesta, the Cuban chair of the G77 plus China group, has said that talks about these details were instead "deadlocked" over issues of - you guessed it - where the money is going and the governance of the fund.

The U.S.'s proposal for the fund to be governed by the World Bank has been rejected by the G77 after "extensive" discussions, the report says. Cuesta has said that the nations seek to have the fund managed elsewhere, but that the U.S. wasn't open to such arrangements. 

Cuesta said: “We have been confronted with an elephant in the room, and that elephant is the US. We have been faced with a very closed position that it is [the World Bank] or nothing.”

Christina Chan, a senior adviser to US climate envoy John Kerry, responded: “We have been working diligently at every turn to address concerns, problem-solve, and find landing zones.” She said the U.S. has been "clear and consistent" in their messaging on the need for the fund. 

Cuesta contends that the World Bank, known for lending to less affluent nations, lacks a "climate culture" and often delays decision-making, hindering quick responses to climate emergencies like Pakistan's recent severe flooding.

The G77 coalition voiced concerns about the World Bank's legal framework potentially limiting the fund's ability to accept diverse funding sources like philanthropic donations or to access capital markets.

With just days left before the UN COP 28 summit, the World Bank insists that combating climate change is integral to its mission and vows to collaborate on structuring the fund.

Tyler Durden Fri, 10/20/2023 - 15:45

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