Category: 3. Business

Analysis: you can expect a simple system of six to eight solar panels to generate about one third of your home’s electricity needs

This article is now available above as a Brainstorm podcast. You can subscribe to the Brainstorm podcast via Apple Podcasts, Stitcher, Spotify or wherever you get your podcasts.

The proverb “Give a man a fish and you feed him for a day; teach him to fish and you feed him for life” has an unlikely resonance in the current fossil fuel crisis, especially when it comes to measures than are needed to help homeowners deal with soaring electricity costs. While giving someone a rebate or discount on their energy bill will help them once, giving them the power to generate their own electricity will endure for their lifetime. This is where an unlikely electricity source for Ireland, in the form of sunshine, could be a lifeline to many families struggling to pay energy bills.

Ireland is known more for wind and waves rather than sunshine, but advances in solar technology and reductions in cost now make it an attractive option for residential electricity generation in Ireland. Solar panels that produce electricity are known as solar photovoltaic (PV) modules. These panels generate electricity when exposed to light and it has been one of the fastest growing power generation technologies worldwide.

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From RTÉ News, a new study has found that solar panels could provide 25% of Ireland’s electricity needs

The systems produce electricity that can be used to power your home appliances and heat water via your immersion. The homeowner won’t notice any difference in how appliances work and there is no need to notify or change your electricity supplier.

Naturally, solar systems need sunlight to work but most will still function on overcast days in Ireland although not at their full capacity. You can expect a simple system of six to eight panels on your roof to generate about one third of your annual electricity needs, with most of this between the months of May and September. This means you will still be relying on your electricity supplier, especially in winter and darker months, but you will be buying less electricity from them overall.

Solar PV systems are sized in technical units called kilowatts (kW) and a simple 2.4kW system would have about six to eight panels. Most small systems of this size do not need planning permission, but you should check with your local authority as rules differ from location to location.

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From RTÉ Radio 1’s Morning Ireland, Dr Paul Deane on how over one million Irish homes have roofs suitable for solar panels

While the fuel in the form of sunlight is free, the installation of the panels isn’t and will cost about €4,000 for a simple system with six to eight panels [2.4kW]. There is a Government grant available to help reduce costs, bringing the overall price down to about €3,000. These are ballpark costs and will vary from supplier to supplier. If you are interested in getting solar panels, it is very important to shop around for several quotes and use a reputable certified installer.

A typical home with six to eight solar panels on the roof could save about €400 per year in electricity bills, with the system paying back for itself in seven to 10 years. The deployment of residential solar PV in Ireland addresses key energy and climate issues such as affordability but also helps Ireland at a national level in terms of Increasing security of supply and reducing the pollution from greenhouse gas emissions.

In UCC, we carried out a study, funded by the Irish Solar Energy Association, to understand how many homes can use sunlight to generate electricity. We were surprised to find that about half the homes in Ireland have potential for this technology and, if all this was achieved, we could produce enough electricity to meet a quarter of all residential electricity demand.

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From RTÉ Radio 1’s Today With Claire Byrne, would solar panels work for your home?

But there are very real challenges in rolling out this technology at scale at a national level. For a start, there is a shortage of skilled workers to do the work. Furthermore, while the economic and environmental arguments for the technology are very compelling, it still requires a significant upfront investment by the homeowner.

In this regard SEAI have a range of grants available to homeowners to reduce costs, but many families will still find the investment prohibitive. This is where Government policy needs to intervene and provide 100% grants to fund solar panels for homes in receipt of fuel allowance as low-income families need the highest level of financial protection during this crisis.

To get the best out of your panels, you will also have to change some behaviours about when you use appliances such as dishwashers and washing machines. If you have a solar system, it is best run these appliances when the sun is shining

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From RTÉ Brainstorm, all you need to know about putting solar panels on your roof

While some homeowners will look to put in a battery system to store any excess electricity, this adds to the costs. However, if you have a hot water or immersion tank, you can set up your solar system to divert surplus electricity to heat your water. In essence this acts like a battery and stores the electricity as hot water, which can be used to offset the use of the immersion for hot showers etc.

Any remaining electricity can be exported to the grid and homeowners can now get paid a small fee for this. But with current high electricity prices, it is best to use as much of your solar generated electricity in your own home as possible.

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The views expressed here are those of the author and do not represent or reflect the views of RTÉ

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For more than a decade, Americans have been steadily drinking less milk each year.

But the latest federal data show sales of milk beverages turned around in 2024, increasing by 358 million pounds or just under 1 percentage point from the previous year to 43.2 billion pounds.

It’s the result of a resurgence in sales of whole milk, which have been trending upward since 2014. The category saw a 3% increase from 2023 and helped offset the continued declines in most other categories, including reduced-fat and skim milk.

Whole milk has benefited from the diet craze around protein driven largely by health and fitness influencers, said Leonard Polzin, dairy markets and policy outreach specialist for the University of Wisconsin-Madison’s Division of Extension.

“The more protein, the better. Consumers are all about that,” Polzin said. “The other portion is kind of a shift towards healthy fats too. So for example, cottage cheese is having a real moment right now.”

Industry data shows whole milk consumption is up in both households with children and those without, according to Karen Gefvert, chief policy officer for Edge Dairy Farmer Cooperative, which represents farmers in Wisconsin and Minnesota.

Gefvert said whole milk has also benefited from increasing consumer interest in whole foods and foods that are minimally processed – a trend that has been promoted by the Trump administration’s Make America Healthy Again agenda.

“There are a ton of really great things in whole milk, and I think that’s resonating with consumers,” Gefvert said.

Federal data going back to 1975 show total U.S. milk sales peaked in 2009 at more than 55.4 billion pounds. That total steadily declined to a record low of 42.8 billion pounds in 2023.

Consumption of plant-based milk alternatives has declined in recent years. But Polzin said it’s hard to know if those consumers are making the shift to dairy or simply cutting back on drinking milk of any kind.

Polzin said increasing milk consumption is especially good for dairy farmers. That’s because milk sold as beverages, known in the industry as fluid milk, has a greater impact on the prices paid to farmers.

But Gefvert said this effect is not as prominent in states like Wisconsin, where most milk is processed into cheese and other products. She said most farmers in the state have a more subdued take on last year’s sales increase.

“It was not significant and is likely just sort of a pause in the inevitable continuous decline in fluid milk sales,” Gefvert said.

She said there is hope that whole milk sales in particular will continue to increase. Congress recently passed federal legislation to reintroduce the option to the National School Lunch Program, which currently requires schools to offer low-fat or skim milk to students. The Whole Milk for Health Kids Act is expected to be signed by President Trump.

Medical experts are divided on whether full fat dairy options, which contain high levels of saturated fat, negatively affect human health.

Earlier this year, a scientific panel that advises the federal government on dietary guidelines concluded there wasn’t enough evidence to change the existing guidance, which recommends Americans drink low-fat or skim rather than whole milk.

This story was produced in partnership with Harvest Public Media, a collaboration of public media newsrooms in the Midwest and Great Plains. It reports on food systems, agriculture and rural issues.

Fort Providence, N.W.T., is now home to a portable shelter and mobile hotspot that could provide coverage to traditional land use areas around the community — but it’s not in use just yet.

The unit was built through a partnership between Deh Gáh Got’îê First Nation and N.W.T.-based telecommunications company SSi Canada, and received a $480,000 grant from the federal government’s Universal Broadband Fund.

The unit is a 10-by-20-foot shipping container, and is powered by a small solar array and backup generator. Half of it contains equipment for mobile coverage and wifi provided by Starlink. The other half is a heated safety shelter that people can sit in. 

SSi Canada calls the structure the Land-Life-Link, or L3.

“If you’re trying to get away from the elements, if you’re trying to get away from an emergency, you can stay there for quite a while,” said Dean Proctor, SSi Canada’s chief development officer.

Proctor told CBC News the unit has been in Fort Providence and fully functional since June. He added it should provide cell service and mobile data over an approximately five-kilometre radius, with some variation depending on the terrain.

“Primarily it’s for people stranded out on the land, so they have communication access if they need to call for help or things like that,” said Greg Nyuli, the executive director at Deh Gáh Got’îê First Nation.

Nyuli said Deh Gáh Got’îê First Nation plans to bring the shelter to a healing lodge downstream of Fort Providence on the Mackenzie River, to provide some connectivity in an area that’s popular for hunting, fishing and harvesting.

But because of low water levels on the river, they likely won’t be able to bring it there on the ice road this winter as planned.

“The access route we usually use in the winter is like totally rocky, because there’s no water,” he explained.

Nyuli said they are now planning to bring the unit downstream on a small barge this summer — though if water levels are low again in the main channel of the Mackenize River, this might not be possible either.

“The only option other than that would be a big helicopter, and we certainly can’t afford that,” he said.

Deh Gáh Got’îê First Nation Chief Michael Vandell said the unit is currently up and running behind the Fort Providence’s Snowshoe Inn.

He said the First Nation is planning to move the unit to outside the local school in the centre of town so students and others can access the wifi it provides more easily. Vandell said the goal is to do this early in the new year.

BRIDGEWATER, N.J., Jan. 2, 2026 /PRNewswire/ — Insmed Incorporated (Nasdaq: INSM), a people-first global biopharmaceutical company striving to deliver first- and best-in-class therapies to transform the lives of patients facing serious diseases, today announced that management will present at the J.P. Morgan 2026 Healthcare Conference in San Francisco, on Monday, January 12, 2026, at 3:00 p.m. PT / 6:00 p.m. ET.

This event will be webcast live and can be accessed by visiting the investor relations section of the Company’s website at www.insmed.com. Webcasts will be archived for a period of 30 days following the conclusion of the live events.

About Insmed

Insmed Incorporated is a people-first global biopharmaceutical company striving to deliver first- and best-in-class therapies to transform the lives of patients facing serious diseases. The Company is advancing a diverse portfolio of approved and mid- to late-stage investigational medicines as well as cutting-edge drug discovery focused on serving patient communities where the need is greatest. Insmed’s most advanced programs are in pulmonary and inflammatory conditions, including two approved therapies to treat chronic, debilitating lung diseases. The Company’s early-stage programs encompass a wide range of technologies and modalities, including gene therapy, AI-driven protein engineering, protein manufacturing, RNA end-joining, and synthetic rescue.

Headquartered in Bridgewater, New Jersey, Insmed has offices and research locations throughout the United States, Europe, and Japan. Insmed is proud to be recognized as one of the best employers in the biopharmaceutical industry, including spending five consecutive years as the No. 1 Science Top Employer. Visit www.insmed.com to learn more or follow us on LinkedIn, Instagram, YouTube, and X.

Contact:

Investors:

Bryan Dunn
Vice President, Investor Relations
(646) 812-4030
[email protected]

Media:

Claire Mulhearn
Vice President, Corporate Communications
(862) 842-6819
[email protected] 

SOURCE Insmed Incorporated

Kamoa-Kakula smelter is Africa’s largest copper smelter with a capacity of 500,000 tonnes of copper per annum

Kamoa-Kakula 2026 sales set to exceed production as 20,000 tonnes of stockpiled copper in concentrate is smelted and sold as 99.7%-pure copper anodes at current record copper prices

Kakula Mine Stage Two dewatering complete; selective mining of eastern side of Kakula Mine recommenced ahead of schedule

Kolwezi, Democratic Republic of the Congo–(Newsfile Corp. – January 2, 2026) –  Ivanhoe Mines (TSX: IVN) (OTCQX: IVPAF) Executive Co-Chairman Robert Friedland and President and Chief Executive Officer Marna Cloete announced that the first copper anodes were produced by Kamoa-Kakula’s on-site, state-of-the-art 500,000-tonne-per-annum direct-to-blister copper smelter on December 29, 2025, approximately five weeks after the commencement of the smelter’s heat-up and one week after the first feed of concentrate.

Watch the video showing first feed of concentrate and casting of the first batch of anodes at the Kamoa-Kakula copper smelter: https://vimeo.com/1150929862/8c8a54cbda?share=copy&fl=sv&fe=ci

Ivanhoe Mines’ Founder and Executive Co-Chairman Robert Friedland commented:

“The first production of copper anodes from our world-class smelter is a defining moment for Kamoa-Kakula… This achievement is the culmination of a $1.1 billion investment, 18 million man-hours of disciplined execution, and an outstanding health and safety record that reflects the professionalism and commitment of everyone involved.

“This facility will proudly deliver the highest-quality Congolese copper anodes to the international markets, setting a new global benchmark for scale, efficiency, and sustainability. I want to extend my sincere thanks to the extraordinary Kamoa Copper team, as well as our contractors and partners from across the world whose expertise, innovation, and teamwork made the design and delivery of this state-of-the-art facility possible. Together, we have built something exceptional that will serve global consumers for generations to come.”

Smelter ramp-up underway to achieve a steady-state annualized rate of 500,000 tonnes of 99.7%-pure copper anode, making it the largest copper smelter in Africa.

The ramp-up of the Kamoa-Kakula copper smelter will continue throughout 2026, with completion expected towards year-end. As announced on December 3, 2025, Kamoa-Kakula’s copper production is estimated at between 380,000 and 420,000 tonnes of copper in 2026, with the mid-point of 400,000 tonnes of copper representing approximately 80% of the smelter’s total capacity.

Kamoa-Kakula’s management team will prioritize the processing of concentrates produced by the Phase 1, 2, and 3 concentrators through the on-site smelter, with any excess concentrate toll-treated at the Lualaba Copper Smelter (LCS), near Kolwezi, in the Democratic Republic of the Congo (DRC).

Heat-up and completion of hot commissioning of the smelter furnace, as well as boiler, steam systems, acid circuit and the concentrate dryer were completed in line with expectations. The furnace successfully reached its operating temperature of 1,250 degrees centigrade (2,282 degrees Fahrenheit) for five days prior to the first feed of concentrate.

Prior to the first feed of concentrate into the smelter, Kamoa-Kakula’s on-site concentrate inventory contained approximately 37,000 tonnes of copper. Total unsold copper in concentrate at the smelter, held in stockpiles and the smelting circuit, is expected to be reduced to approximately 17,000 tonnes during 2026 as the smelter ramps up. Therefore, 2026 copper sales are expected to be approximately 20,000 tonnes higher than copper production as the on-site inventory of unsold copper concentrate is destocked, predominantly during H1 2026. As destocking occurs, Kamoa-Kakula’s management aims to capitalize on near-record-high copper prices.

The installation of the uninterruptible power supply (UPS) facility was completed prior to the first feed of concentrate into the smelter, which took place on December 21, 2025. The 60-megawatt (MW) UPS is designed to provide up to two hours of instantaneous back-up power to the smelter, protecting the operation from voltage fluctuations in the domestic DRC grid. In addition, construction of Kamoa-Kakula’s 60 MW on-site solar (PV) facilities continues to progress well. The solar site, with battery storage, is expected to be the largest of its kind in Sub-Saharan Africa. The solar facilities are expected to be operational from Q2 2026, providing 24 hours a day of uninterruptible power, in addition to the approximately 180 MW of on-site diesel-powered, back-up generator capacity already in place.

A view over the casting wheels during the first batch of anodes produced by the Kamoa-Kakula Copper Smelter on December 29, 2025.

Kamoa-Kakula’s Copper Smelter is the largest copper smelter in Africa with an annualized nameplate capacity of 500,000 tonnes of 99.7%-pure copper anodes.

Kamoa-Kakula’s operating margins are set to expand due to reduced logistics costs from the smelter, as well as sales of by-product sulphuric acid

Kamoa-Kakula’s margins are expected to expand as the smelter ramps up, as concentrates produced by Phase 1, 2, and 3 concentrators are smelted on-site, rather than being exported unbeneficiated. Kamoa-Kakula’s logistics costs are expected to approximately halve as the copper content per truck-load exported more than doubles, from approximately 45% contained copper in concentrate to 99.7%-pure copper anodes. Further savings are expected to be also achieved through the significant revenues generated from sulphuric acid sales.

In addition to the first production of copper anodes, the Kamoa-Kakula smelter also produced its first batch of by-product sulphuric acid. The smelter is expected to produce up to 700,000 tonnes per annum of high-strength sulphuric acid at steady-state operations, which will be sold locally.

Sulphuric acid is in high demand by other mining operations across the Central African Copperbelt, especially following the export ban of acid by Zambia in September 2025. Spot acid prices have reached as high as $700 per tonne in Kolwezi in recent months. The first sale of acid by Kamoa-Kakula has already taken place, with the first delivery expected in the coming weeks.

Construction of copper smelter delivered with industry-leading health and safety record

Kamoa-Kakula’s projects team extended their industry-leading health and safety record during the construction of the smelter. During the 18 million hours worked, only one lost time injury (LTI) was recorded, an exceptionally rare industry achievement. Therefore, the lost-time injury frequency rate (LTIFR) for the delivery of the smelter was approximately 0.054 per million hours worked.

The last project delivered by Kamoa-Kakula’s project team was the Phase 3 concentrator, which was completed in mid-2024 without a single LTI recorded.

Stage Two dewatering of Kakula Mine complete; selective mining on the eastern side commenced ahead of schedule in late December

Stage Two dewatering activities are complete, with the first pair of high-capacity submersible dewatering pumps (Pumps 3 and 4) running dry. As announced on December 3, 2025, following an underground survey, Pumps 3 and 4 were repositioned lower in late November to enable an additional Stage Two dewatering. Since then, the water level has declined by a further 19 metres to the level shown in Figure 1. The second pair of Stage Two pumps (Pumps 1 and 2), which are approximately 20 metres lower in elevation compared with Pumps 3 and 4 are expected to run dry in January 2026.

Stage Three dewatering activities will take over from Stage Two dewatering, and consist of re-commissioning the existing, water-damaged underground horizontal pump stations, which are used for steady-state operations. The rehabilitation work consists of fitting new pump motors, substations and electrical cabling. All required equipment is on site, and installation will begin once access to the horizontal pump stations becomes available.

Figure 1. A schematic of the underground water levels at the Kakula Mine as at December 22, 2025, overlaid with the underground pumping infrastructure.

There is currently 5,600 litres per second of installed pumping capacity at the Kakula Mine, excluding the Stage Two pumping infrastructure. Stage Three dewatering activities are expected to continue into Q2 2026 and will not be on the critical path for Kakula’s mining operations.

In addition, the western side of the Kakula Mine has been dewatered, enabling the mining of higher-grade areas. Head grades from mining areas on the western side of Kakula are expected to increase from 3.5% copper in January to approximately 4.0% copper by the end of Q1 2026. In addition, selective mining on the eastern side of the Kakula Mine began ahead of schedule at the end of December.

Qualified Persons

Disclosures of a scientific or technical nature at the Kamoa-Kakula Copper Complex in this news release have been reviewed and approved by Steve Amos, who is considered, by virtue of his education, experience, and professional association, a Qualified Person under the terms of NI 43-101. Mr. Amos is not considered independent under NI 43-101 as he is Ivanhoe Mines’ Executive Vice President, Projects. Mr. Amos has verified the technical data disclosed in this news release.

Ivanhoe has prepared an independent, NI 43-101-compliant technical report for the Kamoa-Kakula Copper Complex, which is available on the company’s website and under the company’s SEDAR+ profile at www.sedarplus.ca:

• Kamoa-Kakula Integrated Development Plan 2023 Technical Report dated March 6, 2023, prepared by OreWin Pty Ltd.; China Nerin Engineering Co. Ltd.; DRA Global; Epoch Resources; Golder Associates Africa; Metso Outotec Oyj; Paterson and Cooke; SRK Consulting Ltd.; and The MSA Group.

The technical report includes relevant information regarding the assumptions, parameters, and methods of the mineral resource estimates on the Kamoa-Kakula Copper Complex cited in this news release, as well as information regarding data verification, exploration procedures and other matters relevant to the scientific and technical disclosure contained in this news release.

About Ivanhoe Mines

Ivanhoe Mines is a Canadian mining company focused on advancing its three principal operations in Southern Africa; the Kamoa-Kakula Copper Complex in the DRC, the ultra-high-grade Kipushi zinc-copper-germanium-silver mine, also in the DRC; and the tier-one Platreef platinum-palladium-nickel-rhodium-gold-copper mine in South Africa.

Ivanhoe Mines is exploring for copper in its highly prospective, 54-100% owned exploration licences in the Western Forelands, covering an area over six times larger than the adjacent Kamoa-Kakula Copper Complex, including the high- grade discoveries in the Makoko District. Ivanhoe is also exploring for new sedimentary copper discoveries in new horizons including Angola, Kazakhstan, and Zambia.

Information contact

Follow Robert Friedland (@robert_ivanhoe) and Ivanhoe Mines (@IvanhoeMines_) on X.

Forward-looking statements

Certain statements in this release constitute “forward-looking statements” or “forward-looking information” within the meaning of applicable securities laws. Such statements and information involve known and unknown risks, uncertainties, and other factors that may cause the actual results, performance, or achievements of the company, its projects, or industry results, to be materially different from any future results, performance, or achievements expressed or implied by such forward-looking statements or information. Such statements can be identified using words such as “may”, “would”, “could”, “will”, “intend”, “expect”, “believe”, “plan”, “anticipate”, “estimate”, “scheduled”, “forecast”, “predict” and other similar terminology, or state that certain actions, events, or results “may”, “could”, “would”, “might” or “will” be taken, occur or be achieved. These statements reflect the company’s current expectations regarding future events, performance, and results and speak only as of the date of this release.

Such statements include, without limitation: (i) statements that 2026 copper sales are expected to be approximately 20,000 tonnes higher than copper production as the on-site inventory of unsold copper concentrate is destocked, predominantly during H1 2026; (ii) statements that the Kamoa-Kakula smelter is Africa’s largest copper smelter with a capacity of 500,000 tonnes of copper per annum; (iii) statements that total unsold copper in concentrate at the smelter, held in stockpiles and the smelting circuit, is expected to be reduced to approximately 17,000 tonnes during 2026 as the smelter fully ramps up; (iv) statements that the ramp-up of the Kamoa-Kakula copper smelter will continue throughout 2026, with completion expected towards year-end; (v) statements that head grades from mining areas on the western side of Kakula are expected to increase from 3.5% copper in January to approximately 4.0% copper by the end of Q1 2026; (vi) statements that Kamoa-Kakula’s copper production is estimated at between 380,000 and 420,000 tonnes of copper in 2026, with the mid-point of 400,000 tonnes of copper representing approximately 80% of the smelter’s total capacity; (vii) statements that Kamoa-Kakula’s management team will prioritize the processing of concentrates produced by the Phase 1, 2, and 3 concentrators through the on-site smelter, with any excess concentrate toll-treated at the Lualaba Copper Smelter; (viii) statements that Kamoa-Kakula’s 60 MW on-site solar site, with battery storage, is expected to be the largest of its kind in Sub-Saharan Africa and that the solar facilities are expected to be operational from Q2 2026, providing 24 hours a day of uninterruptible power; (ix) statements that once fully ramped up, the smelter’s overall copper recovery is expected to be 98.5%; (x) statements that Kamoa-Kakula’s margins are set to expand as logistics costs approximately halve as the copper content per truck-load exported more than doubles, from approximately 45% contained copper in concentrate to 99.7%-pure copper anodes. Further savings are also expected to be achieved through the significant revenues generated from sulphuric acid sales; (xi) statements that Stage Three dewatering activities are expected to continue into Q2 2026 and will not be on the critical path for Kakula’s mining operations, and; (xii) statements that head grades from mining areas on the western side of Kakula are expected to increase from 3.5% copper in January to approximately 4.0% copper by the end of Q1 2026.

Forward-looking statements and information involve significant risks and uncertainties, should not be read as guarantees of future performance or results, and will not necessarily be accurate indicators of whether such results will be achieved. Many factors could cause actual results to differ materially from the results discussed in the forward-looking statements or information, including, but not limited to: (i) uncertainty around the rate of water ingress into underground workings; (ii) the ability, and speed with which, additional equipment can be secured, if an as required; (iii) the continuation of seismic activity; (iv) the full state of underground infrastructure; (v) uncertainty around when future underground access can be fully secured; (vi) the fact that future mine stability cannot be guaranteed; (vii) the fact that future mining methods may differ and impact on Kakula operations; and (viii) the ultimate conclusion of the assessment of the cause of the seismic activity at Kakula and the impact of same on the final mining plan at the Kamoa Kakula Copper Complex. Additional factors also include those discussed above and under the “Risk Factors” section in the company’s MD&A for the three and nine months ended September 30, 2025, and its current annual information form, and elsewhere in this news release, as well as unexpected changes in laws, rules or regulations, or their enforcement by applicable authorities; changes in the rate of water ingress into underground workings; recurrence of seismic activity; the state of underground infrastructure; delays in securing full underground access; changes to the mining methods required in the future; the failure of parties to contracts with the company to perform as agreed; social or labour unrest; changes in commodity prices; and the failure of exploration programs or studies to deliver anticipated results or results that would justify and support continued exploration, studies, development or operations.

Although the forward-looking statements contained in this news release are based upon what management of the company believes are reasonable assumptions, the company cannot assure investors that actual results will be consistent with these forward-looking statements. These forward-looking statements are made as of the date of this news release and are expressly qualified in their entirety by this cautionary statement. Subject to applicable securities laws, the company does not assume any obligation to update or revise the forward-looking statements contained herein to reflect events or circumstances occurring after the date of this news release.

The company’s actual results could differ materially from those anticipated in these forward-looking statements as a result of the factors outlined in the “Risk Factors” section in the company’s MD&A for the three and nine months ended September 30, 2025, and its current annual information form.

To view the source version of this press release, please visit https://www.newsfilecorp.com/release/279364

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Off track for clean power?

As a cultural historian who has worked with and lectured on the drinks industry for many years I was asked to write a book about post-war Britain and the drinks that made it. I immediately knew I had to include Babycham – a post-austerity tipple that had made Britain smile.

Britain in the early 1950s was gradually emerging from the shadow of war and was dealing with bankruptcy and post-war shortages. By the time of Queen Elizabeth II’s coronation in 1953, British manufacturing was getting back on its feet.

In that year, a little-known Somerset brewery, Showerings, hit upon a novel idea: offer cash-strapped Britons sick of the grey years of austerity a festive, sparkling alcoholic tipple that was cheap but fun. Thus was born Babycham, the celebratory drink that looked like champagne, but wasn’t.

I have distinct memories of my mum drinking the sparkling beverage in the 1960s, sometimes with brandy as a cheap, working-class alternative to the classic champagne cocktail. And who can forget those wonderful, deer-themed champagne coupes which Babycham distributed, and which are now collectors’ items.

As I write in my book Another Round, it was originally named “Champagne de la Poire” by its creators, Francis and Herbert Showering of Shepton Mallet in Somerset. Babycham was a new alcoholic perry – a cider made from pears. It had the modest strength of 6% alcohol-by-volume and came in both full-sized bottles and fashionable, handbag-sized four- and two-ounce versions.

At sixpence a bottle, Babycham’s bubbles come at a fraction of the price of genuine French bubbly – a luxury that very few could afford. Babycham came to epitomise the brave new world of mid-1950s Britain – British ingenuity still seemed to lead the world, and anything seemed possible.

Marketing with fizz

Babycham’s innovative brand design, marketing methods and advertising techniques brought flashy and flamboyant American techniques to the staid world of British beverages as its makers exploited not just the expanding potential of magazines and radio but, crucially, the revolutionary medium of television advertising. Perhaps most importantly, it was also the first British alcoholic drink to be aimed squarely at women.

Showerings and their advertising guru Jack Wynne-Williams made Babycham into the first British consumable to be introduced through advertising and marketing, rather than marketing an existing product. Their eye-catching new baby deer logo featured in the ad campaign of autumn 1953 and has been with us ever since. And it was equally prominent when their groundbreaking debut TV ad in 1956 made Babycham the first alcoholic brand to be advertised on British television.

In order to convey the idea that Babycham provided a champagne lifestyle at a beer price, Showerings advised their (largely female) customers that it was best served in an attractive and undeniably feminine French champagne coupe. Coupes were soon being customised by Showerings, who plastered them with the brand’s distinctive new deer logo and thereby created an instant kitsch collectable. In this way, Babycham offered the aspirational female Briton of the 50s and 60s a fleeting illusion of glamour and sophistication at the price of an average pub tipple.

All of this Americanised marketing paid handsome dividends. Babycham’s sales tripled between 1962 and 1971. These bumper sales enabled the Showerings to be acquired by drinks leviathan Allied Breweries in 1968, and after the merger Francis Showering was appointed as a director of the new company.

It was only in the early 1980s that Babycham’s sales began first to fall, and then to plummet. During this decade the drinks market was becoming more sophisticated and diverse. Women were turning more to wine and cocktails than to retro tipples made from sparkling pear juice.

However, after a period in the doldrums, the Babycham brand is back. In 2016, a younger generation of Showerings bought back the family’s original cider mill in Shepton Mallet and sought to revive their famous sparkling perry, relaunching Babycham in 2021.

If it is remembered at all, it’s now associated with celebrations such as birthdays or Christmas. No longer seen as a regular indulgence. The Babycham brand and its winsome fawn logo do seem rather old-fashioned today but in an age of nostalgia for the Britain of the past it could be ripe for a renaissance.

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As China heads into the new year it will start rolling out its 15th five‑year plan, this one is for 2026-2030.

Beijing is doubling down on greening its economy, and aims to hit two major climate goals: “carbon peaking”, where carbon dioxide emissions have reached a ceiling by 2030, and “carbon neutrality”, where net carbon dioxide emissions have been driven down to zero by 2060.

Yet, China’s green push sits uneasily with its energy realities: coal still provides about 51% of its electricity as of mid‑2025, underpinning China’s difficulty in greening its energy system swiftly. Here are five major challenges that will shape China’s green transition as it moves into 2026.

1. Energy transmission and wastage

Imagine standing in western China (for instance in Tibet, Xinjiang and Qinghai), which produces a lot of solar and wind energy. On bright and windy days, these installations generate vast amounts of clean electricity. Yet much of that power goes to waste.

China’s grid can only handle a limited load, and when renewable generation peaks, it risk overloading the power network. So grid operators respond by telling energy producers to dial down output, which is a process called “curtailement”. The result is that electricity from the west often fails to reach eastern economic hubs, such as Beijing, Tianjin, Shandong, Jiangsu, Shanghai, Zhejiang, Fujian and Guangdong, where demand is greatest.

China needs to invest heavily in the ways to transport and store excess energy. The State Grid Corporation of China claims that it will be spending 650 billion yuan (£69 billion) in 2025 to upgrade the power network, and perhaps much more in subsequent years.

The challenge here is sustaining these capital-intensive projects while the broader economy still grapples with the lasting effects of the 2021 property crisis.

2. Cutting coal without blackouts

Even as China vows to go green and be a world leader in environmental energy, it continues to expand its coal capacity, and has added enough new coal-fired power stations in 2024 to power the UK twice over per annum. This apparent contradiction stems from concerns over energy security.

Beijing is determined to avoid a repeat of the blackouts and power shortages of 2020–2022. Coal provides dependable, round‑the‑clock power that renewables cannot yet fully replace. Yet the steady expansion of coal capacity undercuts China’s climate pledges and highlights ongoing tensions between China’s president, Xi Jinping’s, dual carbon goals and the country’s pressing energy demands, which raises questions about how far political ambition can stretch against economic reality.

3. Taming overcapacity without hurting growth

China’s vast manufacturing strength, which was once an asset, is now posing a problem. The rapid expansion of solar, wind, and electric vehicle industries has created overcapacity across the clean‑tech sector. Factories are producing more panels, turbines, and batteries than the domestic market can absorb. This has created a cut-throat price war, where companies sell at below cost price, which erodes company profits.

Beijing must find a balance between restraining overproduction without choking growth in green industries. This balancing act is politically sensitive, as local governments depend on these industries to create jobs (7.4 million in 2023), and generate substantial revenue. It was estimated that in 2024 green industries contributed 13.6 trillion yuan to China’s economy or 10% of the country’s GDP.

4. Trade tensions from overcapacity

China’s surplus of clean tech such as cheap solar panels, electric vehicles (EVs), and batteries, have triggered trade tensions abroad. In 2023 and 2024, the European Union investigated allegations of Chinese subsidies being poured into EVs, wind turbines and solar panels. Tariffs of up to 35.3% were placed on Chinese EVs. However, tariffs on Chinese solar panels and wind turbines have not been imposed so far.

But, on January 1 2026 the EU’s Carbon Border Adjustment Mechanism (CBAM) comes into effect. The CBAM is a carbon tax that Europeans will pay if imported goods are made using high carbon emissions. While the tax does not explicitly target EVs and solar panels, it will cover carbon-intensive materials used in their production, such as steel and aluminium, which are made using coal-fired plants.

What this means is Chinese clean tech might lose its competitive edge in the European market as customers are driven away from its products. Industrial players might rely on exports to stay afloat given the highly competitive nature of China’s domestic green market, but the CBAM is likely to undermine China’s green industry.

5. Fulfilling green targets locally

Chinese local governments are formally responsible for putting Beijing’s climate policies into practice, but many are expected to implement these policies largely on their own. While provincial authorities typically have more fiscal resources and technical expertise, city-level governments within each province often don’t have the funds to do so, which makes it difficult to deliver on green initiatives in practice.

At the same time, even when local authority leaders are told to achieve climate‑related targets, their career advancement remains closely linked to conventional economic performance indicators such as GDP growth and investment.

All of this helps explain the continued enthusiasm for new coal‑fired power projects. They are framed not only as a fail‑safe in case renewables and grids cannot meet rising demand, but also as avenues for local employment, fixed‑asset investment and fiscal revenue.

China’s continued greening in 2026 will be challenged by all of these issues.

Karachi, January 2, 2026: In a year marked by return of economic stability, K-Electric (KE), Pakistan’s only vertically integrated power utility, showed steady progress across its businesses of generation, transmission, distribution, and supply, alongside continued investments in digital transformation and customer engagement.

Moonis Alvi, KE CEO, said: “K-Electric has always focused on customer satisfaction, and we will continue to facilitate our customers with utmost dedication. Karachi is our responsibility and we will continue to serve the city with all our effort.

“The revised MYT has presented new challenges, but we will balance the best of what we have to offer to both the city and the company.”

The year-end business performance round-up shows KE’s focus on ensuring reliable power for Karachi’s households, commercial hubs, and industrial units, while catering to the city’s unique operational and demand dynamics.

Peak demand

Karachi, Pakistan’s largest and most populous city, recorded a peak demand of 3,563 MW during June 2025 which was ably met with a peak supply of 3,545 MW, demonstrating KE’s grid resilience during peak summer conditions. Average demand for the year (January-November) hovered around 2,353 MW, reflecting the city’s expanding economic activity and urban growth. Monthly average demand figures fluctuated around 1,470 MW in winters and 2,920 MW during summers reflecting seasonal variations in consumption patterns.

Generation up to the task

KE’s generation infrastructure played a key role in meeting Karachi’s seasonal demand variations, particularly during peak summer months when consumption rises sharply.

During 2025, KE’s generation portfolio supported the city’s growing energy landscape. The utility continued to optimise existing assets, while advancing planning and regulatory processes for future capacity additions aligned with affordability and sustainability goals.

KE also accelerated its transition to cleaner energy. Through competitive bidding, the utility secured Pakistan’s lowest renewable tariffs, ranging between PKR 8.9 and PKR 11.6 per unit for its 640 MW clean energy projects. The Bid Evaluation Reports for projects at Dhabeji, Winder, and Bela were approved by NEPRA in May 2025 and are set to add green energy to KE’s generation mix capacity over the coming years, contingent upon necessary regulatory approvals.

Transmission continues with strength

KE continued to strengthen Karachi’s power supply infrastructure and secure access to surplus, economically viable energy from the national grid. During the year, the KKI grid and its associated interconnection facilitated an increased offtake capacity of up to 2,000 MW from the national grid, enhancing the overall stability and resilience of the network alongside wheeling of cheaper power to the economic hub of the country.

Crackdown on electricity theft

KE continued to prioritise network reliability and loss reduction, while addressing challenges stemming from electricity theft and non-payment in high-loss pockets.

Over 25,000 kunda removal drives were carried out across the serviced region and nearly 320,000 kilogrammes of illegal wiring was removed till November-end.

Customer facilitation

As part of its customer-centric approach, KE also organised 310 customer facilitation camps across the city. These camps provided on-ground assistance for billing, payments, new connections, and meter-related queries.

Collectively, these initiatives contributed to recoveries amounting to PKR 409 million, reflecting the role of engagement and awareness in improving payment behaviour and service access.

Industrial, net-metered connections

Supporting Karachi’s industrial base remained a key priority during the year. KE provided 339 new industrial connections, which added a cumulative sanctioned load of 136.4 MW to the network, till November-end. These connections supported sectors including manufacturing, textiles, FMCG, ports, and export-oriented industries, reinforcing Karachi’s role as Pakistan’s economic engine.

KE also continued to facilitate customer participation in renewable energy through its net metering process. Between January and November 2025, the utility had connected 9,676 net-metered customers, adding over 230 MW in available capacity. Net metering approvals and interconnections were processed in line with prevailing regulatory frameworks, contributing to distributed generation within the city.

Digitisation

Digital transformation continued to reshape customer experience and operations. KE launched Kineto, Pakistan’s first generative AI-powered chatbot by a power utility, designed to provide instant, 24/7 support and streamline customer interactions across key service areas. The chatbot now sees nearly 3,000 chats a day on average. Billing information, outage updates, and service queries remain main queries.

KE also became one of the first power utilities in the region to implement SAP S/4HANA RISE, strengthening cybersecurity, transparency, and data-driven decision-making.

Customer engagement through digital channels rose to 2.7 million digitally connected customers, compared with 1.94 million the previous year. E-billing adoption increased to 13 percent from 8 percent, while nearly 70 percent of all bills were paid through online/alternate digital channels.

During the year, KE was also awarded top honours at the Effie Awards Pakistan 2025, securing the prestigious Grand Prix for Campaign of the Year along with a Gold Effie in the Small Budget category for its energy conservation campaign ‘Farq Parta Hai’.

Meanwhile, by the start of December, over 1.2 million customers were actively using the KE Live App, a number that stood at 1.0 million at the start of the year.

Energy Progress & Innovation Challenge (EPIC)

Committed to fostering creativity, innovation, and localisation in the energy sector, KE also held the Energy Progress & Innovation Challenge (EPIC) with the finale being held in June 2025.

It united entrepreneurs, academia, researchers, and think tanks to develop solutions for the energy sector. EPIC received over 250 entries centered around AI-driven forecasting using edge computing for improved demand prediction and smarter dispatch, machine learning–based asset health diagnostics to monitor cables and transformers and reducing outages, IoT-enabled fleet tracking for faster field operations and response times, real-time energy theft detection through AI-based anomaly identification, renewable integration models assessing PV impact, and optimising battery storage for grid stability.

MYT

During the year, KE’s Multi-Year Tariff was also approved, establishing a framework for investments, performance benchmarks, and cost recovery.

Subsequently, the determination was revised downwards by NEPRA. This revision has been challenged before the court and the same is pending adjudication. Considering the revision, company is assessing pathways to ensure reliable power supply for Karachi.

During the year, NEPRA also approved write-off claims amounting to approximately PKR 50 billion for the period FY 2017-2023, recognising these as legitimate and prudent costs following due review.

As KE moves into the new year, the utility remains focused on strengthening infrastructure, supporting industrial growth, improving recoveries, and expanding digital access, all while balancing affordability, reliability, and regulatory compliance.

Cell culture

U87 and HEK cell lines were cultured at 37 ^∘C and 10% CO₂ in DMEM D6429 media (Sigma-Aldrich) supplemented with 10% fetal bovine serum (FBS), 50 μg ml⁻¹ streptomycin and 50 units ml⁻¹ penicillin.

T2 cells and Nalm6 cells were cultured at 37 ^∘C and 10% CO₂ in RPMI 1640 (Sigma-Aldrich) supplemented with 10% FBS, 50 μg ml⁻¹ streptomycin and 50 units ml⁻¹ penicillin.

All cell lines were obtained from the ATCC except for Nalm6, which was provided by Crystal Mackall.

Primary human T cells were isolated from leucocyte cones and cultured at 37 ^∘C and 10% CO₂ in RPMI 1640 (Sigma-Aldrich) supplemented with 10% FBS, 50 μg ml⁻¹ streptomycin, 50 units ml⁻¹ penicillin and 50 U ml⁻¹ IL-2.

Lentivirus production

HEK 293T cells (0.8 million) were seeded in a 6-well plate (Day 1) and incubated overnight. Cells in each well were co-transfected (Day 2) using X-tremeGENE HP (Roche) with 0.8 μg of the appropriate lentiviral transfer plasmid encoding an antigen receptor (1G4 TCR or c259 TCR) and the lentiviral packaging plasmids: pRSV-Rev (0.25 μg), pMDLg/pRRE (0.53 μg) and pVSV-G (0.35 μg). The media were replaced 18 h following transfection (Day 3). At 24 h after the media exchange, the supernatant from one well was collected, filtered and used for the transduction of 1 million human T cells (Day 4).

Production of TCR transduced primary human T cells

T cells were isolated from anonymized leucocyte cones (Day 3) purchased from the NHS Blood Donor Centre at the John Radcliffe Hospital (Oxford University Hospitals). Due to the anonymized nature of the cones, biological sex and gender were not variables in the present study and were therefore randomized, hence the authors were blinded to these variables. RosetteSep Human CD8⁺ Enrichment Cocktail (STEMCELL Technologies) was used for cytotoxic T cells, or CD4⁺ T Cell Enrichment Cocktail (STEMCELL Technologies) for helper T cells. The enrichment cocktail was added at 150 μl ml⁻¹ of sample and incubated at r.t. for 20 min. The sample was diluted with an equal volume of PBS and layered on Ficoll Paque Plus (Cytiva) density gradient medium at a 0.8:1 ratio (Ficoll:sample).

The sample was centrifuged at 1,200 g for 30 min (brake off). Cells at the interface of the Ficoll media and plasma were collected (buffy coat) and washed twice (centrifuged at 500 g for 5 min). Cells were resuspended in complete RPMI media supplemented with IL-2 (50 U ml⁻¹) at a density of 1 million cells per ml. Dynabeads Human T-Activator CD3/CD28 (ThermoFisher) were added (1 million beads per ml) and cells were incubated overnight.

One million cells were transduced with the filtered lentiviral supernatant (Day 4). On Day 6 and on Day 8, 1 ml of medium was removed and replaced with 1 ml of fresh medium. On Day 9, Dynabeads were removed using a magnetic stand (6 days following isolation). Cells were resuspended in fresh media every other day at a density of 1 million per ml and used for co-culture experiments. At 17 days following isolation, T cells were discarded.

CRISPR/Cas9 knockout of T cell proteins

Cas9 ribonucleoproteins (RNPs) were prepared by mixing 8.5 μg of TruCut Cas9 protein v2 (ThermoFisher) with 150 pmol of sgRNA mix (Truguide Synthetic gRNA, ThermoFisher) for each target gene (Supplementary Table 4) and Opti-MEM (Gibco) to a final volume of 5 μl. The RNPs were incubated for 15 min at r.t.

One million freshly isolated T cells were washed with Opti-MEM (Gibco) and resuspended at a density of 20 million per ml. The T cells were mixed with the RNPs and transferred into a BTX Cuvette Plus electroporation cuvette (2 mm gap, Harvard Bioscience). The cells were electroporated using a BTX ECM 830 Square Wave Electroporation System (Harvard Bioscience) at 300 V for 2 ms. Immediately following electroporation, the cells were transferred to complete RPMI media supplemented with IL-2, and Dynabeads Human T-Activator CD3/CD28 (ThermoFisher) were added.

Negative selection of T cell knockout cells

T cells with residual target protein expression were depleted by antibody staining and bead pulldown. T cells were resuspended in MACS buffer (PBS, 0.5% BSA, 2 mM EDTA) at a density of 100 million cells per ml. Cells were stained with 5 μl of the corresponding PE-labelled antibody per million cells for 15 min at 4 ^∘C, washed with MACS buffer and resuspended at a density of 100 million cells per ml. A volume of 1 μl of MojoSort anti-PE nanobeads (Biolegend) was added per million cells and incubated on ice for 15 min. The cells were washed with MACS buffer and the beads were pulled down magnetically. The supernatant containing the negatively selected cells was collected.

Cellular co-culture assays

U87 cells (50,000) in 100 μl of DMEM were seeded per well in a 96-well flat-bottom plate and incubated overnight. Alternatively, 100,000 T2 cells were placed in each well of a 96-well flat-bottom plate. Peptides were diluted in DMEM to the appropriate concentration, added to each well containing cells and incubated for 60 min at 37 ^∘C and 10% CO₂. The media were discarded and 50,000 T cells were added to each well in 200 μl of RPMI medium. Cells were incubated for 20 h at 37 ^∘C and 5% CO₂. Supernatants were collected for cytotoxicity and ELISA analysis. A volume of 25 μl of 100 mM EDTA PBS was added to each well containing the cells and samples were incubated for 5 min at 37 ^∘C and 5% CO₂. Cells were detached by thoroughly pipetting each well and transferred to a 96-well V-bottom plate.

Lck chemical inhibition assay

U87 cells (50,000) in 100 μl of DMEM were seeded per well in a 96-well flat-bottom plate and incubated overnight. T cells were treated with the appropriate concentration of A-770041 for 1 h. The DMEM media were discarded and 50,000 A-770041-treated T cells were added to each well in 200 μl of RPMI media. Cells were incubated for 4 h at 37 ^∘C and 5% CO₂. Supernatants were collected for cytotoxicity and ELISA analysis, and T cells were analysed for activation markers as in other co-culture assays.

Flow cytometry

The following fluorophore-conjugated mAbs were used: CD45 (Biolegend, clone HI30), CD3 (Biolegend, clone OKT3), 4-1BB (Biolegend, clone 4B4-1), CD69 (Biolegend, clone FN50), CD8α (Biolegend, clone HIT8), CD4 (Biolegend, clone RPA-T4), CD43 (Biolegend, clone CD43-10G7), CD11α (Biolegend, clone TS2/4), CD5 (Biolegend, clone UCHT2), CD2 (Biolegend, clone TS1/8) and TCR Vβ13.1 (Biolegend, clone H131).

Cells were stained for 20 min at 4 ^∘C, washed with PBS and analysed using a BD X-20 or a Cytoflex LX flow cytometer (Beckman Couter). Data were analysed using FlowJo v.10, RRID:SCR008520 (BD Biosciences) and GraphPad Prism, RRID:SCR002798 (GraphPad Software).

Cytotoxicity assay

Target cell lines were engineered to express the Nluc luciferase⁵⁷. A 2 mM coelenterazine (CTZ) stock solution was prepared in methanol, aliquoted and stored at −80 ^∘C. Supernatant from co-culture assays was mixed at a 1:1 ratio with PBS 10 μM CTZ, and luminescence was read using a SpectraMax M3 microplate reader (Molecular Devices).

Cytokine ELISA

Invitrogen Human IFNγ ELISA kits (ThermoFisher) were used following manufacturer protocol to quantify levels of cytokine in diluted T cell supernatant. A SpectraMax M3 microplate reader (Molecular Devices) was used to measure absorbances at 450 nm and 570 nm.

Longitudinal killing assay

mCherry positive A375 cells were seeded in a 96-well flat-bottom plate and incubated overnight in 100 μl of DMEM at 37 ^∘C and 5% CO₂. To normalize differences in TCR transduction across different batches, 50,000 a3a or c259 TCR positive T cells were used as the starting concentration, and they were serially diluted to the appropriate effector:target (E:T) ratios. For each E:T ratio, 100 μl of T cells were plated in triplicate. The mCherry positive A375 cell number was quantified every 2 h using an xCELLigence RTCA eSight system (Agilent).

Surface plasmon resonance

All SPR experiments were carried out at the Dunn School SPR facility using our published method²⁴. The c259 TCR/pMHC steady-state binding affinities were measured on a Biacore T200 SPR system (GE Healthcare) with a CAP chip using HBS-EP as running buffer. The CAP chip was saturated with streptavidin and biotinylated pMHCs were immobilized to the desired level. A titration of the TCR was flowed through at 37 ^∘C. The reference flow cell contained CD58 immobilized at levels matching those of pMHCs on the remaining flow cells. The signal from the reference flow cell was subtracted (single referencing) and the average signal from the closest buffer injection was subtracted (double referencing). Steady-state binding affinity was calculated by fitting the one site-specific binding model (Response = B_max [TCR]/(K_D + [TCR])) on GraphPad Prism to double-referenced equilibrium resonance units (RU) values. The B_max was constrained to the inferred B_max from the empirical standard curve generated by plotting the maximal binding of a conformationally sensitive pMHC antibody to the maximal TCR binding (B_max).

Pooled 9-mer peptide library

A library of pooled randomly synthetized 9-mer peptides was produced by Peptide Protein Research. This library was composed of all natural amino acids, except cysteine, as previously described⁵⁸. The library has a theoretical diversity of 19⁹ peptides.

U87 cells (50,000) in 100 μl of DMEM were seeded per well in a 96-well flat-bottom plate and incubated overnight. The 9-mer pooled peptide library was diluted in DMEM to 100 μM, added to each well containing cells and incubated for 60 min at 37 ^∘C and 10% CO₂. T cells (50,000) were added to each well in 200 μl of RPMI medium. Cells were incubated for 20 h at 37 ^∘C and 5% CO₂. Supernatants were collected for cytotoxicity analysis. In each independent biological experiment, three technical measurements were taken and averaged.

Positional scanning peptide library SPR

To prepare pMHC complexes presenting the local peptide library, a disulfide-stabilized variant of the human MHC-I protein HLA-A*02:01 (DS-A2) was used⁵⁹. The DS-A2 protein was produced as described previously⁵⁹. Briefly, the DS-A2 and β2-microglobulin (β2m) subunits were produced in E. coli as inclusion bodies and solubilized in 8 M urea. The protein was then refolded in the presence of GlyLeu, a dipeptide that binds with low affinity to the peptide-binding cleft. The refolded DS-A2–β2m complexes were purified by size exclusion chromatography on a Superdex S75 10/300 column (GE Healthcare/Cytiva) in HBS-EP buffer (10 mM HEPES pH 7.4, 150 mM NaCl, 3 mM EDTA and 0.05% Tween 20). Local-library peptides were loaded by incubating the DS-A2–β2m complex with each peptide for 2 h at r.t. The pMHC complexes were stored at 4 ^∘C until use within 24 h.

Soluble c259 TCR was produced as separate TCRα and TCRβ chains in E. coli. Both chains were recovered as inclusion bodies, solubilized in 100 mM Tris-HCl (pH 8.0), 8 M urea and 2 mM dithiothreitol, and then stored in aliquots at −70 ^∘C. For refolding, 30 mg of each TCR chain was added to 1 l of refolding buffer (150 mM Tris-HCl (pH 8.0) 3 M urea, 200 mM Arg-HCl, 0.5 mM EDTA, 0.1 mM PMSF) and stirred for 1 h at 4 ^∘C. This was followed by dialysis in 10 l 10 mM Tris-HCl (pH 8.5) buffer for 3 days in total, with the dialysis buffer changed after 1 day. The refolded c259 TCR was purified using anion exchange chromatography (HiTrap Q HP, Cytiva), followed by size exclusion chromatography (Superdex 200 Increase, Cytiva) in HBS-EP buffer. Purified c259 was used within 48 h.

High-throughput affinity measurements of c259 TCR binding to MHC loaded with the peptide library were performed using LSA or LSA^XT (Carterra). Each pMHC was immobilized via biotin–streptavidin binding on a different spot of the SAHC30M biosensor (Carterra) for 20 min, resulting in immobilization levels between 200 and 900 RUs. Measurements were performed in HBS-EP buffer at 37 ^∘C. A 2-fold dilution series of c259 TCR was prepared in HBS-EP buffer, with the highest concentration between 100–130 μM. Starting with the highest dilution, increasing concentrations of c259 were injected over the chip for 5 min, followed by 5–10 min of dissociation, without regeneration. Afterwards, a β2m specific antibody (clone B2M-01 (ThermoFisher) or BBM.1 (Absolute Antibody)) was injected for 10 min. The resulting data were analysed using Kinetics Software (Carterra). Any spikes were removed from the data before referencing against empty control spots or spots immobilized with CD86 at matching immobilization levels. The final injection in a series 6 buffer injections before TCR injection was subtracted from the data for double referencing. Subsequently, the steady-state binding RU was calculated by taking the average RU from over 20 s.

Steady-state analysis was performed to obtain the TCR–pMHC affinity (K_D) values. First, steady-state data were fitted with a one site-specific binding model (Response = B_max [TCR]/(K_D + [TCR])), with K_D and B_max unconstrained. We then constructed an empirical standard curve using high-affinity pMHCs (K_D < 20 μM) to relate maximal anti-β2m binding to TCR B_max. Next, steady-state data for all pMHCs were fitted with a one site-specific binding model, with B_max constrained to the B_max inferred from the empirical standard curve. We excluded K_D values for peptides, where we observed little or no anti-β2m binding responses, indicating that the pMHC complex was unstable and lost the peptide over time (indicated as N/A in Supplementary Table 2). We further excluded K_D values for pMHC that produced a TCR binding response of less than 5 RU (indicated as non-binders (NB) in Supplementary Table 2).

Data analysis

EC₅₀ was calculated as the concentration of antigen required to elicit 50% of the maximum response determined for each condition individually, whereas P₁₅ was calculated as the concentration of antigen required to elicit 15% of the maximum activation for the experiment.

We have used P₁₅ for two reasons. First, P₁₅ always corresponds to the concentration of peptide required to activate 15% of T cells, independent of the maximum responses. In contrast, EC₅₀ is the concentration of peptide required to activate 50% of the maximum response (that is, normalized to the maximum of wild type or knockout). In other words, two antigens with the same antigen potency as measured by EC₅₀ values may produce a different percentage of activated T cells if their maximum response (E_max) differ. In this case, the antigens would have different antigen potencies as defined by P₁₅. Second, the use of P₁₅ does not require the dose–response curve to saturate, enabling accurate estimates of P₁₅ from lower-affinity interactions. This measure of potency was previously used in ref. ²⁴ to study ligand discrimination.

The study is largely focused on comparing antigen sensitivity using EC₅₀ or P₁₅ measures, which we have found to display standard deviations of 0.2 (on log-transformed values). The smallest effective size that we aimed to resolve was 3-fold changes (a difference of 0.47 on log-transformed values), and a power calculation shows that this can be resolved with a power of 80% (⍺ at 0.05) using three samples in each group. Therefore, all experiments relied on a minimum of 3 independent donors.

Reporting summary

Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.