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Today Novartis announced that it will terminate the acquisition of STING agonist ADU-S100 from Aduro, primarily with Novartis' own PD-1 antibody spartalizumab, and the combination therapy development with Squibb Yervoy, but Aduro is also ready to continue to develop this product with Keytruda in stage 2 clinical head and neck cancerThe ADU-S100/spartalizumab combination produced only 9% response rate in phase 1 clinical, and the ADU-S100/Yervoy combination produced only 7% response rate in PD-1 drug-resistant blacksAduro shares are down another 10 per cent to $1 a share today, down from $40 at its peakthe analysis of the drug source
Aduro was one of the pioneers of immunotherapy, and its Lister Bacterial Platform (LADD) produced crX-207, a pancreatic cancer tumor vaccine based on mesopretin, but failed in phase III in 2017ADU-S100 should be the earliest human STING agonist, another STING agonist called DMXXA, although the animal efficacy is good but only activates the mouse STING, the binding force with human STING is very lowIn 2015, IO and Biotech both bought the product in a bubble-era period with a down payment of $200 million and a $500 million mileage paymentNovartis also acquired a 2.7 percent stake in Aduro for $25 million and invested $25 million to develop the productSTING is an intracellular detection of warning signalmechanisms discovered in the last 10 years or soAny double-stranded DNA activates an enzyme called cGAS to produce a natural STING agonist, cGAMP, which activates the immune system and clears dangerous cellsNormal double-stranded DNA is in the nucleus, but tumors and damaged cells may have DNA flowing into the cytoplasmSTING and cells indicate that the TLR family is the main component of the natural immune system, STING agonists are similar to TLR agonists with high toxicity, ADU-S100 requires intra-tumor administrationEven the two STING agonists that are now in clinical practice are very generic, with few one-sided effects, and only with PD-1 antibodies can they see some signalsAlthough many patients had lower doses (one of the early clinical goals was to find the maximum tolerable dose), these data showed that the first generation of STING agonist treatment windows were smallerIn previous years, Glaxo has found a class of STING agonists that can be systematically drugged, but so far there is no clinical datathe company that benefited the most from STING was IFM, which sold STING agonists and antagonists at high prices to Squibb and Novartis, respectivelySTING remains one of the key targets of concern to the pharmaceutical industry, with at least 10 companies having different types of STING agonists, but the use of key components such as STING requires a lot of explorationIntra-tumor injection solves the problem of selectivity to some extent, and other mechanism drugs through this route of administration has shown some early efficacy, such as last month's in-tumor administration of the TLR9 agonist CMP-001 unilateral compound in the evil black all produced a good responseCompound combinations may also be a strategy, but it is debatable whether the same lack of selective PD-1 drugs is the best combination partnerLow levels of activation of STING may make tumor cells more sensitive to certain targeted drugs, and the CRISPR system knocks out different genes that may find that low-level STING activation is not tolerated, providing a direction for highly selective STING combination therapiesOf course, there are many techniques for targeted delivery, but this may require that the drug itself be sufficiently activeIn any case, now that broad-spectrum cancer drugs have become a contradictory term, STING must be more selective in order to make a drug.