AstraZeneca PLC

Over decades, antibodies have established themselves as a key therapeutic modality for a wide range of diseases. But antibodies as they are found in nature did not evolve to be used as drugs, says James Lazarovits, co-founder and CEO of Archon Biosciences. These proteins became drugs because scientists co-opted them to do things. One of the limitations of currently available antibodies is the therapeutic window, which is the dose range within which a drug achieves its therapeutic effect without also causing dose-limiting toxicity. Lazarovits describes this window as the interplay between how much of the drug gets to where you want it to go versus how much goes where you don’t want it to go (thereby causing toxic effects). The technology of Archon changes the size and shape of an antibody, adjusting how a therapy gets where it needs to go in the body, what it does when it gets there, and whether or not it stays there. The Seattle-based startup emerged from stealth this past week with $20 million in funding for R&D of what could become a new class of antibody drugs. The field of antibody drug R&D includes efforts in multivalency, which is the ability to bind to multiple sites on the same target, and multispecificity, which is binding to two or more different antigens. These antibodies can be good for certain application, but not as good for others, Lazarovits said. Rather than engineering an antibody by altering the order of amino acids that make up a protein or adding different arms or multiple binding domains, Archon designs antibodies in a way that controls their structures. Archon calls its drugs antibody cages, or AbCs. These antibodies are made in a way that plugs into the established format for manufacturing antibodies, simply adding an additional work step at the end of the manufacturing process. But this additional step gives the antibody features it did not have in the first place. Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech An AbC offers tunability that is not found naturally in antibodies, Lazarovits said. More than just turning a target on or off, the AbC’s structure can adjust how much. Antibodies often require secondary signals to activate. While that’s achievable and controllable in a closed system, within a patient and across patient populations it become more difficult. Lazarovits said the structure of the AbC can autonomously activate pathways without needing something to happen elsewhere. “The structure that we make changes how we actually activate the biology of a cell surface,” he said. “It’s not whether the antibody binds the target, it’s how it binds to the target.” The Archon technology comes from the University of Washington’s Institute for Protein Design, which is led by David Baker, the professor of biochemistry awarded the 2024 Nobel Prize in Chemistry for his work in computational protein design. Computational protein companies that have spun out of the institute include vaccine developer Icosavax, which was acquired by AstraZeneca last year for $800 million up front, and A-Alpha Bio, whose technology for analyzing protein-protein interactions has landed partners such as Bristol Myers Squibb. Archon co-founder George Ueda worked with Baker for more than a decade. Lazarovits said their research initially aimed to develop proteins that had never existed in nature. Then they aimed to design proteins with unique structures. From there, they aimed to see if those structures could do something. presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum Lazarovits entered the picture about five-and-a-half years ago bringing a background in antibody delivery. Baker gave both Ueda and Lazarovits faculty positions. Their research landed $7 million in grant funding to further develop what became the AbC platform. The scientists were able to generate preclinical data to show what problems these novel antibodies could address. This research was published in 2021 in the journal Science. Lazarovits said the research also helped the scientists understand what kind of capital would be needed to use this new antibody science to develop novel drugs. Archon was incorporated in early 2023. Archon is not yet disclosing the therapeutic indications it is researching. But Lazarovits said the programs the startup has selected address well-characterized targets that have been elusive to the pharmaceutical industry. Based on preclinical research, Archon understands the contingencies for activating and deactivating its selected targets. What that could mean for an Archon drug is similar activity compared to an already available medication but fewer side effects, increased potency, or some combination of both, Lazarovits said. He added that the company is pursuing acute indications, not chronic therapies. By focusing on well-known, sought-after targets that have remained elusive, the “check box” of data Archon needs is very standardized, Lazarovits said. The company knows the data it needs to collect and it knows what to show to demonstrate how its antibodies are differentiated. Knowing all of this at the outset means generating the data can happen quickly. The startup’s strategy resonated with investors. Archon’s seed financing was led by Madrona Ventures, a Seattle-based venture capital firm that has invested in several artificial intelligence-enabled biotech companies, such as Ozette and Nautilus Biotechnology. Other participants in the Archon financing include DUMAC Inc., Sahsen Ventures, WRF Capital, Pack Ventures, Alexandria Venture Investments, and Cornucopian Capital. Lazarovits said the funding gives Archon runway of about two years. More than generating data to demonstrate the science of AbCs, Archon will use its new capital to build a business case. Eventually, the startup aims to strike up partnerships with larger companies, Lazarovits said . When that happens, he wants to have enough data to know which assets to partner out and which ones to keep build value for the young company. Conversations with pharma companies and additional investors are already underway, Lazarovits said. “Because this is such an amenable technology for partnerships, we’re getting our ducks in a row,” he said. “If you try to do everything, you’re going to do everything pretty poorly.” Image: Archon Biosciences

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here . Earnings season is in full swing, and we’ve got recaps for you for all the Big Pharma companies that reported this week. Plus, news of an AbbVie neuro buyout, new semaglutide data in MASH and experts discuss what an RFK Jr.-led crusade against public health agencies would look like for biopharma. — Max Gelman Biotech and pharma leaders are grappling with Donald Trump’s embrace of Robert F. Kennedy Jr. , who has extensively criticized vaccines and the drug industry, routinely embraces many conspiracy theories, and has made threats to force out FDA staff. Zachary Brennan has the details here. Rounding up the biggest earnings news of the week, Eli Lilly lowered the top end of its full-year revenue guidance by $600 million on Wednesday, triggering a significant one-day drop in stock price. Lilly attributed the guidance to “investing heavily in increasing the supply of tirzepatide .” Meanwhile, Novartis has recorded an $800 million impairment after reviewing “certain clinical trial data” just five months after closing its $2.9 billion deal for MorphoSys . CEO Vas Narasimhan remains confident and touted the company’s overall M&A track record. And Pfizer made its first substantive comments on the activist investor pushing for changes at the company this week while talking up the strength of its other programs including its plans in obesity . AstraZeneca said its China president Leon Wang is under investigation in the country, though not much is known about the nature of the investigation. Throughout the year, AstraZeneca has reiterated how important China is to the overall health of its business, with $1.6 billion of its revenue (about 12%) coming from the country. Last week, it was reported that a BeiGene executive was under investigation in China for alleged ties to an insurance fraud case while she was at AstraZeneca. In its third acquisition of the year, AbbVie said it will pay $1.4 billion in cash to buy the Phase 1 Alzheimer’s and neuroscience biotech Aliada Therapeutics . The deal adds to AbbVie’s big bet on CNS medicines after spending $8.7 billion last year to acquire Cerevel Therapeutics . Aliada’s study is investigating intravenous (or under-the-skin) doses of the anti-pyroglutamate amyloid beta antibody. The startup delayed data for a psilocybin program that’s one of the leaders in psychedelic drug development, pushing one study back about six months and another roughly one year. CEO Kabir Nath told Max Bayer that there had been delays in accruing data in the earlier study, citing a “logistical complexity” like having to arrange for therapists to participate in sessions. The company will lay off 30% of its employees, and its chief communications officer and chief legal officer/general counsel will both depart. SPOTLIGHT Q&A: Jade CEO talks about reverse merger and IgAN drugs ‘Imitation is best form of flattery’: Regeneron CEO comments on Amgen’s Eylea biosimilar Atlas of tumors reveals in 3D how cells change into cancer MORE IN R&D MORE IN PHARMA MORE IN STARTUPS MORE IN DEALS MORE IN FDA+ MORE IN MANUFACTURING MORE IN HEALTH TECH

A panel of three judges on the US Court of Appeals for the Third Circuit didn’t offer too many hints at which side it would take as it heard oral arguments on Wednesday from a trio of last-ditch challenges to the new government drug price negotiations consolidated together by Bristol Myers Squibb, Johnson & Johnson and AstraZeneca. The appeal comes as federal judges earlier this year shot down a series of challenges to the Inflation Reduction Act’s negotiations provision brought by Bristol Myers, J&J, AstraZeneca , Boehringer Ingelheim and Novo Nordisk . The government in August completed its first round of negotiations with all 10 participating drugs. Lawyers for BMS, J&J and AstraZeneca on Wednesday again argued that the companies don’t really have a choice with the government-set negotiation process. Paying a steep penalty if they refuse the negotiation or accepting a debarment from the entire Medicare and Medicaid program are not actual options, they contended. “All we want is to not be compelled to sell a drug under threat of government sanction,” Jones Day’s Yaakov Roth, representing BMS, said at the oral argument . He also referred to the negotiations as a “gun to the head,” noting that companies don’t really have an option. But the judges pushed back, saying the companies would not be put out of business by the negotiations program, as they can still sell on the private market. HHS’ lawyer Lindsey Powell and CMS’ lawyer Catherine Padhi argued that the companies are voluntarily participating and still making profits off the negotiated prices. Some of the participants of the first round of negotiations softened their tone and none of the companies indicated that the negotiated prices would immediately affect their bottom lines. Kevin King, J&J’s lawyer, took issue with “maximum fair price” as a term that CMS compels companies to use to describe the price that the government sets for participating drugs. He said usage of the term “fair price” makes the process look more like a negotiation. That message has been picked up by government officials saying that this program has “brought manufacturers to the table,” King added, noting that President Joe Biden touted the negotiations at the State of the Union address. “By telling the manufacturers that they need to tell the world that the prices set by CMS, which by statute have to be highly discounted, are the maximum fair prices, the program is requiring manufacturers to indict their own conduct,” King said. Circuit Judge Arianna Freeman asked King if companies are prevented from issuing a press release saying a negotiated price is not fair. King said they are not prevented from issuing such a statement, but that doesn’t change the language that the government is using in its contracts. “You can achieve the same maximum prices for the drugs without putting words in our mouth,” King said. HHS and CMS’ lawyers stressed that the term “maximum fair price” is a specific legal term and should not be understood according to any colloquial meaning around the idea of fairness. Circuit Judges Thomas Hardiman and Peter Phipps also referred to the term “maximum fair price” as “oxymoronic” and “Orwellian” at different points in the oral argument, but it remained unclear if they were buying into the drugmakers’ position on the language.