Kezar Life Sciences, a 2015 spinout from Amgen, is laying off 41% of its workforce and pausing all preclinical R&D in a bid to extend its cash runway into late 2026 and move select clinical programs forward, the biotech said Tuesday.
There are also several executive shakeups: Kezar said co-founder John Fowler will resign as CEO on Nov. 7 and former president and CSO Christopher Kirk will take over as CEO. CMO Noreen Henig is resigning on Oct. 6 and Zung To, the senior VP of clinical development operations, will take over trial execution and development operations.
The freed-up cash will be used to get data readouts for its candidates. This includes PALIZADE, Kezar’s Phase IIb trial in lupus nephritis with its drug zetomipzomib, as well as Phase I data for KZR-261 in solid tumors that is expected in 2024.
The company added that it is looking for ways to reduce the number of planned expansion cohorts to conserve cash resources.
Kezar previously expected its cash runway to last through the beginning of 2026, according to William Blair analysts. Its stock $KZR was trading down nearly 10% in premarket trading at $1.04.
Topline data for its Phase IIa PORTOLA trial with zetomipzomib for autoimmune hepatitis is expected in mid-2025 and topline data from PALIZADE is expected in mid-2026.
Kezar’s preclinical efforts, like its protein secretion platform and candidate KZR-540, are halted for now, though Kezar said it is looking to partner or license on its protein platform.
“These difficult but necessary decisions to streamline our operations and align resources around our clinical programs should put us on a path to long-term success, extending our runway past key data points, particularly the readout for our PALIZADE trial,” Fowler said in a statement.
TD Cowen analysts called the move to focus on clinical programs “necessary” and “makes much more strategic sense” in a note on Wednesday morning. The analysts added that investors had been concerned about the company’s ability to fund operations through the release of Phase IIb data for zetomipzomib, “and therefore we expect the restructuring to remove the financing overhang on the stock. We think the cash runway extension and previously announced collaboration with Everest Medicines will help set Kezar up for success” in zetomipzomib’s “potentially pivotal” Phase IIb trial in lupus nephritis, which the analysts called the “major value-driver” for Kezar.
Kezar announced its licensing agreement with China-based Everest Medicines in late September. Everest is licensing zetomipzomib in Greater China, South Korea and some Southeast Asian countries with a $7 million upfront payout and up to $125 million in clinical and commercial milestone payments as well as royalties. Everest will help Kezar with a Phase IIb zetomipzomib trial in patients with active lupus nephritis that began earlier this year.
In Kezar’s latest SEC financial filing in August, the company said it had $236.6 million in cash, cash equivalents and marketable securities as of June 30, though the company added it had operating losses and negative cash flows since its inception and anticipated that it will “continue to incur losses for at least the foreseeable future.” Kezar’s net loss was $46.5 million for the six months ended June 30, with an accumulated deficit of $295.4 million.preclinical south korea china
Ancient Egypt had far more venomous snakes than the country today, according to our new study of a scroll
Ancient texts are still teaching us new things about the prevalence of wildlife.
How much can the written records of ancient civilisations tell us about the animals they lived alongside? Our latest research, based on the venomous snakes described in an ancient Egyptian papyrus, suggests more than you might think. A much more diverse range of snakes than we’d imagined lived in the land of the pharaohs – which also explains why these Egyptian authors were so preoccupied with treating snakebites!
Like cave paintings, texts from early in recorded history often describe wild animals the writers knew. They can provide some remarkable details, but identifying the species involved can still be hard. For instance, the ancient Egyptian document called the Brooklyn Papyrus, dating back to around 660-330BC but likely a copy of a much older document, lists different kinds of snake known at the time, the effects of their bites, and their treatment.
As well as the symptoms of the bite, the papyrus also describes the deity associated with the snake, or whose intervention might save the patient. The bite of the “great snake of Apophis” (a god who took the form of a snake), for example, was described as causing rapid death. Readers were also warned that this snake had not the usual two fangs but four, still a rare feature for a snake today.
The venomous snakes described in the Brooklyn Papyrus are diverse: 37 species are listed, of which the descriptions for 13 have been lost. Today, the area of ancient Egypt is home to far fewer species. This has led to much speculation among researchers as to which species are being described.
The four-fanged snake
For the great snake of Apophis, no reasonable contender currently lives within ancient Egypt’s borders. Like most of the venomous snakes that cause the majority of the world’s snakebite deaths, the vipers and cobras now found in Egypt have just two fangs, one in each upper jaw bone. In snakes, the jaw bones on the two sides are separated and move independently, unlike in mammals.
The nearest modern snake that often has four fangs is the boomslang (Disopholidus typus) from the sub-Saharan African savannas, now only found more than 400 miles (650km) south of present-day Egypt. Its venom can make the victim bleed from every orifice and cause a lethal brain haemorrhage. Could the snake of Apophis be an early, detailed description of a boomslang? And if so, how did the ancient Egyptians encounter a snake that now lives so far south of their borders?
To find out, our masters student Elysha McBride used a statistical model called climate niche modelling to explore how the ranges of various African and Levantine (eastern Mediterranean) snakes have changed through time.
Niche modelling reconstructs the conditions in which a species lives, and identifies parts of the planet that offer similar conditions. Once the model has been taught to recognise places that are suitable today, we can add in maps of past climate conditions. It then produces a map showing all the places where that species might have been able to live in the past.
On the trail of ancient snakes
Our study shows the much more humid climates of early ancient Egypt would have supported many snakes that don’t live there today. We focused on ten species from the African tropics, the Maghreb region of north Africa and the Middle East that might match the papyrus’s descriptions. These include some of Africa’s most notorious venomous snakes such as the black mamba, puff adder and boomslang.
We found that nine of our ten species could probably once have lived in ancient Egypt. Many could have occupied the southern and southeastern parts of the country as it then was - modern northern Sudan and the Red Sea coast. Others might have lived in the fertile, vegetated Nile valley or along the northern coast. For instance, boomslangs might have lived along the Red Sea coast in places that 4,000 years ago would have been part of Egypt.
Similarly, one entry of the Brooklyn Papyrus describes a snake “patterned like a quail” that “hisses like a goldsmith’s bellows”. The puff adder (Bitis arietans) would fit this description, but currently lives only south of Khartoum in Sudan and in northern Eritrea. Again, our models suggest that this species’ range would once have extended much further north.
Since the period we modelled, a lot has changed. Drying of the climate and desertification had set in about 4,200 years ago, but perhaps not uniformly. In the Nile valley and along the coast, for instance, farming and irrigation might have slowed the drying and allowed many species to persist into historical times. This implies that many more venomous snakes we only know from elsewhere might have been in Egypt at the time of the pharaohs.
Our study shows how enlightening it can be when we combine ancient texts with modern technology. Even a fanciful or imprecise ancient description can be highly informative. Modelling modern species’ ancient ranges can teach us a lot about how our ancestors’ ecosystems changed as a result of environmental change. We can use this information to understand the impact of their interactions with the wildlife around them.
Wolfgang Wüster receives funding from the Leverhulme Trust.
Isabelle Catherine Winder does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.treatment africa
Tornadoes in the UK are surprisingly common and no one knows why
Britain doesn’t have huge violent twisters like the US. But it does have lots of little tornadoes.
A small tornado recently passed through the town of Littlehampton on England’s south coast. Strong winds smashed windows, moved cars and left one person injured.
You might associate tornadoes with the plains of the central US, but they’re surprisingly common in the UK too – albeit smaller and weaker. In fact, my former PhD student Kelsey Mulder found that the UK has about 2.3 tornadoes per year per 10,000 square kilometres. That’s a higher density than the US, which as a whole has just 1.3 per 10,000 square km.
The numbers are higher for American states in “Tornado Alley” such as Oklahoma (3.6) or Kansas (11.2). Nonetheless, a random location in the UK is more likely to experience a tornado than a random location in the US.
The data isn’t perfect, however. Tornadoes cannot be observed by satellites and need to be close to weather radars, which can detect the rotation. Thus, most observations are made by humans who then have to report them to the relevant weather service. “Storm-chasers” follow most tornadoes on the American plains, but underreporting may be an issue elsewhere.
Most tornado research has focused on the US, where forecasting and early-warning systems are advanced. There is considerably less research on UK tornadoes. Over the past 12 years, my research group has tried to address this by shedding light on where and when UK tornadoes occur, what causes the storms that produce them and how we can better predict them.
England has three ‘tornado alleys’
Whereas many tornadoes in the US plains occur within a few weeks during the spring, UK tornadoes can occur throughout the year. The UK’s tornado alley is really three regions, most in southern England: an area south of a line between Reading and London with a maximum near Guildford, locations southwest of Ipswich and a line west and south of Birmingham.
These regions have probabilities of experiencing a tornado within a 100 square km area of somewhere between 3% and 6% per year, meaning they could see one as often as every 15 to 30 years.
These tornadoes aren’t as violent as the more extreme ones in the US, but the damage can still be substantial. In July 2005, a large tornado in Birmingham caused £40 million in damages and injured 39. Fortunately, no one was killed. People have died in the past though, for example a strong tornado in South Wales in 1913 killed three.
Although the Birmingham tornado was the most damaging tornado on that day, two others were recorded across the British Isles. Indeed, around 70% of UK tornado days have at least two reports, and 13% produce three or more.
We refer to such days as tornado outbreaks, with the largest-ever UK tornado outbreak occurring on 23 November 1981, producing 104 tornado reports from Anglesey to Norwich.
What causes tornadoes
We still don’t know exactly why the UK has so many weak tornadoes. We do know that “supercells” – rotating thunderstorms tens of kilometres across – form the largest tornadoes in the US but occur less frequently in the UK. Instead, tornadoes in the UK tend to be formed from lines of storms along cold fronts.
Although millions of dollars have been spent researching supercell thunderstorms in the US, there is an increasing awareness that these linear storms also require investigation on both sides of the Atlantic. Our group has been trying to understand what causes some of these parent storms to begin to rotate and eventually spawn tornadoes.
So far, my former PhD student Ty Buckingham and I have been able to identify certain conditions where the wind direction changes abruptly. In such cases, an instability may develop where small perturbations grow into rotating vortices a kilometre or more across, regularly spaced along the front. Such vortices are thought to be the precursor for tornadoes.
Identifying the conditions for this so-called “horizontal shearing instability” should mean we can better predict when and where the parent storms that produce the tornadoes form. But understanding this instability is not the only answer. Other tornado-producing storms do not appear to be associated with this instability, so we still have more to learn.
The next step is understanding how the tornadoes themselves form. For that, we will need both fortuitous observations of such tornadoes forming close to Met Office radars and powerful computer programs that are able to model the atmosphere down to a scale of tens of meters.
Recent advances in computing and our collaborations with colleagues in engineering may yet reveal the secrets of UK tornadoes.
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David Schultz receives funding on this topic from the Natural Environment Research Council (UK) and has received funding from the Risk Prediction Initiative.uk
How smaller businesses can become net-zero influencers and enablers
SMEs could help the UK maintain its position as a climate change champion and ensure a long-term future for all businesses, large or small
What if all of the UK’s 48,000 hairdressing salons and barbershops started sharing water and energy-saving advice with their clients, alongside a clipper cut or a wash and blow dry? Previous studies have demonstrated that hairdressers can shape customers’ environmental behaviour with guidance they can trust and that relates to their everyday lives.
And it’s not just hairdressers. Cafes and restaurants are also addressing food-related emissions with carbon labelling schemes and more sustainable menu choices.
Recruiting smaller businesses to support the drive for net zero makes a lot of sense. More than half of the UK’s business emissions are estimated to come from its 6 million small and medium-sized enterprises (SMEs – companies with less than 250 employees). As the authors of a recent OECD report argue, there’s “no net zero without SMEs”.
But the decarbonisation of smaller firms has only recently attracted serious attention from policymakers, through initiatives such as the UK Business Climate Hub. And while criticism of Rishi Sunak’s watering-down of net-zero policies has united environmental campaigners with some company bosses and investors, it may not be enough to keep SMEs and their emissions in the spotlight.
SMEs are important as energy consumers, and there is an increasing focus on the carbon they emit directly, or that is embedded in their products and services. However, as highlighted in a recent study I worked on with colleagues at Oxford and Sheffield Hallam universities, smaller businesses can also help cut emissions as behavioural “influencers” and “enablers” of change.
How SMEs can help meet net zero goals
SMEs could have a vital role as enablers by helping with the wider adoption of low-carbon technologies. The scope of this type of activity is vast. For example, leading-edge innovations like the Belfast Maritime Consortium’s high-speed, zero-emission passenger ferry (which is launching a pilot scheme in 2024) could help lots of commuters to cut their daily travel emissions.
In addition, many thousands of plumbers and electricians are already playing essential intermediary roles as advisors and installers of more established technologies, such as electric vehicle chargers and heat pumps.
Persistent challenges and hopeful signs
Businesses need to adopt low-carbon technologies and practices to improve productivity, remain competitive and attract staff. The scale and complexity of this challenge varies greatly between sectors. But all businesses could benefit from a more joined-up support framework to help them achieve their goals.
In fact, many smaller businesses are effectively flying in the dark. A recent study estimates that just 1% of SMEs in England are accessing net-zero business support. Our research on support arrangements for SME decarbonisation points to large variations in provision across the four UK nations and between different industry sectors.
Scotland has provided consistent support to SMEs over the last decade, for example, with expert energy audits and subsidised grants available. By contrast, smaller businesses in England have not had access to a national funding programme for building energy efficiency.
Similarly, while SMEs in industries such as food and hospitality are relatively well represented by trade associations that can provide more tailored net-zero advice, we have identified significant issues with access to business support in other sectors.
SMEs operating in large industrial supply chains, for example, often have to navigate an array of regulations and measures from different government departments that do not always appear to be speaking to one another. This generates cost and confusion for many smaller businesses as they struggle to find the right support.
Taking SMEs more seriously
The government’s net-zero review, chaired by Chris Skidmore MP and published in January 2023, was commissioned to identify a pathway to meet the UK’s net-zero target by 2050. It provided a clear set of policy actions designed to trigger an “ambition loop” in which government policy and private sector leadership reinforce each other to increase climate action even further.
But while Skidmore mentions SMEs, there are three key areas where more radical change is needed to help them make a real impact on the UK’s decarbonisation goals:
1. Information and signposting
The review proposed a “Help to Grow Green” campaign, offering information, resources and vouchers for SMEs to plan and invest in the net-zero transition. The UK government’s Department for Energy Security and Net Zero is piloting a new digital energy advice service to help SMEs navigate the maze of competing information sources. But to be really effective, tailored advice and meaningful support is crucial – a balance that’s difficult to achieve in practice.
2. Energy efficiency
Skidmore also called for SMEs to be included in tax reforms to accelerate uptake of energy-efficient technologies. Initiatives of this kind could also help drive improved SME productivity – a longstanding government goal. However, there are few signs of this kind of fiscal incentive in the pipeline right now, at least at a national level.
3. Carbon skills gap
The review highlighted skills gaps in many specialist areas, such as carbon auditing, as well as across sectors and places. A step-change in investment in further education colleges in particular is needed to expand the number of courses, apprenticeships, and knowledge-exchange initiatives. Again, this would help business productivity while also promoting net-zero targets.
The UK’s SME population can make a massive difference to the delivery of the country’s carbon targets, but it will require a more concerted effort. The government must take the lead, working with sector- and place-based organisations.
The agenda is already mapped out in some detail, but delivery is another matter. There is a lot to learn from existing best-practice examples across the four nations, and by expanding our understanding of SMEs and their multiple roles as net-zero consumers, influencers and enablers.
Richard K. Blundel has received funding from ESRC and UKERC.grants uk
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