Cycle on Jul 3, 2026

I will start by listing the topic's open threads to see what questions or watches we are tracking, and then I will search for the latest consequential science and health news from the past week (since our current date is July 3, 2026).

I will perform a targeted web search to identify recent, consequential health, medical, and science developments that occurred in late June and early July 2026. I'll search for major drug approvals, clinical trial readouts, vaccine developments, or infectious disease outbreaks, keeping an eye on our active watches (such as the FDA advisory committees, Capricor, Replimune, or other major clinical readouts).

I see several interesting recent developments: 1. "5 FDA decisions to watch in the third quarter of 2026 | BioPharma Dive" -> I should fetch this to see which FDA decisions are coming up and if they relate to any of our watches or require new ones. 2. "FDA accepted the first in silico drug development tool as part of its ISTAND program" in June 2026. This is a very interesting regulatory science breakthrough. 3. Skyrizi (risankizumab) was approved on June 26, 2026, for children 6+ with moderate-to-severe plaque psoriasis or active psoriatic arthritis, making it the first IL-23 inhibitor approved for children. 4. Amgen recalled nearly 1 million bottles of its heart failure drug Corlanor (ivabradine) Class II recall in late June / early July 2026. 5. "Zoldonrasib combos, including with Daraxonrasib, yield high response rates in PDAC" (July 2026). Let's search more about the "5 FDA decisions to watch in the third quarter of 2026" and "in silico drug development tool ISTAND program" to get solid primary details. I'll search for the BioPharma Dive article and the FDA's ISTAND announcement.

I will fetch the BioPharma Dive article "5 FDA decisions to watch in the third quarter of 2026" to find out exactly what those five decisions are, as they will likely contain key regulatory updates for our watches or new findings.

I have some highly rich information now. Let's see what we can do with our watches: 1. **Moderna's mFlusiva (mRNA-1010)**: - Our watch `019edcf0-1d32-70e1-9a3e-6825808b2370` is for "FDA regulatory decision on Moderna's mFlusiva mRNA flu vaccine" with a fire date of August 5, 2026. This is covered here: "mRNA-1010 ... A decision will come by Aug. 5." The watch is still in the future, so it hasn't fired yet. 2. **Capricor's deramiocel**: - Our watch `019f061f-f34a-7079-a276-d216329928b2` is for "FDA Cellular, Tissue, and Gene Therapies Advisory Committee meeting scheduled for July 29, 2026, to discuss Capricor's BLA for deramiocel in DMD cardiomyopathy." The article mentions "The FDA is expected to make a decision by Aug. 22." (PDUFA date). This is a great confirmation. 3. **Celcuity's gedatolisib**: - PDUFA date of July 17, 2026. This is a brand new, highly consequential Q3 2026 FDA decision for advanced breast cancer. 4. **Takeda's oveporexton**: - PDUFA date expected "before the end of September [2026]" for Type 1 narcolepsy. This is a major orexin-stimulating drug with $2-3B peak sales potential. 5. **Merck's enliclitide** (previously written as enlicitide/enliclitide): - Oral PCSK9 inhibitor. Expected approval in 2H 2026. Let's do a search on the "FDA accepted the first in silico drug development tool as part of its ISTAND program" in June 2026. This is a major regulatory milestone. Let's find out what tool was accepted and what it does.

Let's fetch the FDA's statement on this breakthrough ISTAND tool. This is a very significant piece of regulatory science news from June 2026.

This is an excellent, major milestone for AI and regulatory science. The FDA, under the ISTAND program, accepted the first Letter of Intent (LOI) for an *in silico* (AI-driven) drug development tool to predict Drug-Induced Liver Injury (DILI). This aligns with the push for New Approach Methodologies (NAMs) and the 3Rs (replacement, reduction, and refinement) of animal testing. Let's do a search on other major recent science or public health updates. For example, some news about: - The USDA screwworm fly response (we have a watch on this, let's see why it's in the news today). - The "Skyrizi" approval for pediatric patients (June 26, 2026). - The "Zoldonrasib" combos in metastatic pancreatic cancer. - Any major disease outbreak or public health moves. Let's search for the USDA screwworm updates to see if our watch fired or if there's a major development. Our watch is `019ec32d-6d1a-725d-9d28-251b38e8d928` ("USDA $750M sterile screwworm fly facility operational launch in Texas", fire date 2027-12-31). Let's search why "screwworm.gov" is appearing in the results today.

This is a massive public-health and agricultural crisis unfolding! Let's fetch the Texas Public Radio article or the Border Report article to see what is happening with the screwworm outbreak, the status of the sterile fly facility (which is one of our watches!), and the emergency quarantines. I will fetch `https://www.tpr.org/public-health/2026-07-03/31-confirmed-new-world-screwworm-infestations-texas-tracker-and-what-you-need-to-know` and `https://www.wkrg.com/news/border-report-live-screwworm-facility-not-moving-fast-enough-cuellar-says/amp/`. Let's fetch the first one first.

Let's fetch the other article to see what Representative Cuellar says about the sterile fly facility. This is very relevant to our watch `019ec32d-6d1a-725d-9d28-251b38e8d928`. Let's fetch `https://www.wkrg.com/news/border-report-live-screwworm-facility-not-moving-fast-enough-cuellar-says/amp/`. Wait, the URL has `/amp/` at the end; let's fetch it, or try without `/amp/` if it fails. Let's try the exact URL returned by search.

This is extremely relevant! The New World screwworm outbreak has grown to 31 confirmed infestations (30 in Texas and 1 in New Mexico) since the first U.S. case was detected on June 3, 2026. This is the first outbreak in the U.S. since it was eradicated in 1966. Moreover, Representative Henry Cuellar criticized the slow pace of construction for the $610 million sterile fly facility at Moore Air Force Base in Edinburg, Texas (our watch `019ec32d-6d1a-725d-9d28-251b38e8d928` is titled "USDA $750M sterile screwworm fly facility operational launch in Texas", we should update the cost to $610 million or keep the $750M estimate and note this). The Edinburg facility is not expected to be completed until late 2027. Meanwhile, the U.S. and Mexico opened a new facility in Chiapas, Mexico, releasing 50 million sterile flies per week. Let's check if there are any other major drug approvals or clinical updates. Let's search for "Skyrizi" approval in June 2026 to see if we should write a finding on that. Wait, let's also search for "Amgen recall Corlanor" to see what that Class II recall is about. Let's search for "Zoldonrasib" as well. Let's do a search.

Let's fetch the AbbVie press release on Skyrizi's pediatric approval to get the exact quotes and details. This is the first IL-23 inhibitor approved for pediatric use in psoriatic disease in the US. Let's fetch `https://news.abbvie.com/2026-06-26-SKYRIZI-R-risankizumab-rzaa-Now-FDA-Approved-for-Pediatric-Use-in-Psoriatic-Disease`. This is a highly consequential drug approval (Skyrizi is one of the world's top-selling immunology blockbusters).

Awesome! Let's review what we have: 1. **New World Screwworm Outbreak**: This is a major update to our tracking of the screwworm. The outbreak has reached 31 confirmed infestations (30 in Texas and 1 in New Mexico) as of July 3, 2026, marking the first U.S. outbreak since 1966. Meanwhile, Texas has issued strict emergency quarantines across 21 counties. Crucially, U.S. Rep. Henry Cuellar criticized the slow pace of construction for the $610 million sterile fly facility in Edinburg, Texas (our watch `019ec32d-6d1a-725d-9d28-251b38e8d928` is directly affected because he states it "won't be ready until 2027" and "is not moving fast enough"). I can record an event for this watch: it is an ongoing process watch rather than one_shot, or we can record that we are tracking it. Wait, the watch itself is a one_shot for the "operational launch" with a fire date of 2027-12-31, which is consistent with the late 2027 target mentioned by Cuellar. Let's record an event on thread `019ec32d-6d1a-725d-9d28-251b38e8d928` to log this update. 2. **FDA ISTAND In Silico DDT Program**: On June 3, 2026, the FDA accepted the first-ever Letter of Intent (LOI) for an *in silico* (AI-driven) drug development tool designed to predict Drug-Induced Liver Injury (DILI) under its Innovative Science and Technology Approaches for New Drugs (ISTAND) program. 3. **AbbVie's Skyrizi Pediatric FDA Approval**: On June 26, 2026, the FDA approved Skyrizi (risankizumab-rzaa) for children 6 years and older with moderate-to-severe plaque psoriasis or active psoriatic arthritis. It is the first and only IL-23 inhibitor approved in the U.S. for pediatric patients under 40 kg. Let's check if there are other threads we can resolve or update. Let's see if there is any update on: - Sobi BLA resubmission for NASP (nanoencapsulated sirolimus plus pegadricase) in uncontrolled gout. - Amgen Tavneos FDA hearing submission (extended deadline July 29, 2026). - Capricor's deramiocel in DMD cardiomyopathy. We know from the BioPharma Dive article that the FDA Cellular, Tissue, and Gene Therapies Advisory Committee meeting is scheduled for July 29, 2026 (or around then) and the PDUFA date is August 22, 2026. This is a great update, but the advisory committee meeting itself hasn't happened yet (it's July 29). - Replimune's RP1 in advanced melanoma. The BioPharma Dive article notes that the FDA has revived several previously rejected programs, including Replimune ("previously spurned programs"). Let's check if there is an update on the Advisory Committee meeting or resubmission. Let's do a search on Sobi's BLA resubmission or Replimune's RP1 to see if any of these occurred in the last week.

Ah! Sobi received a CRL on Friday, June 26, 2026, for NASP (nanoencapsulated sirolimus plus pegadricase) in uncontrolled gout. The CRL cited third-party manufacturing deficiencies (CMC and contract manufacturing facility concerns). This is extremely important, as it explains *why* the watch `019f1ab8-b786-7130-9ce1-ccf00ee61d03` was created ("Monitor Sobi's resubmission of the BLA for NASP..."). The CRL was issued on June 26, 2026, and Sobi is working with its contract manufacturer and plans to meet with the FDA to discuss resubmission. Since Sobi has not yet resubmitted, the watch is still active and has not fired. Let's check if there is any update on Replimune's RP1 or the advisory committee. Our watch `019f0620-007b-7dab-87b4-0363a2496ea1` is for "Monitor the FDA advisory committee meeting scheduled for late July 2026 to discuss Replimune's resubmitted BLA for RP1 in advanced melanoma, ahead of the August 2, 2026 PDUFA target action date." Let's see if there are any updates on this.

This is an excellent set of updates! On June 26, 2026, Replimune announced that the FDA accepted its BLA resubmission for RP1 (vusolimogene oderparepvec) in combination with nivolumab (Opdivo) for advanced melanoma. The FDA deemed it a complete, Class 1 response and set a PDUFA target decision date of August 2, 2026. The FDA also notified the company that it will convene an advisory committee meeting in late July 2026 to discuss the application. This fits perfectly with our prior finding "The Post-Makary FDA Pivot: Reversals, Resubmissions, and a Return to Advisory Committees" (slug: `fda-regulatory-pivot-advisory-committees-capricor-replimune`). We can update this prior finding with these high-stakes June 26 updates for both Sobi (which received a CRL on June 26) and Replimune (whose BLA was accepted on June 26 with an August 2 PDUFA date and late July AdCom). Let's organize our notes: 1. **The Post-Makary FDA Pivot: Reversals, Resubmissions, and a Return to Advisory Committees** (slug: `fda-regulatory-pivot-advisory-committees-capricor-replimune`) - We will update this note to include: - The FDA's formal acceptance of Replimune's BLA resubmission on June 26, 2026, with a PDUFA date of August 2, 2026, and an AdCom planned for late July. - The FDA's CRL for Sobi's NASP on June 26, 2026, due to third-party contract manufacturing deficiencies (and Sobi's plan to meet with the FDA). - The BioPharma Dive Q3 outlook detailing Capricor's deramiocel, which has a PDUFA date of August 22, 2026, following the positive Phase 3 Hope-3 trial results. 2. **New World Screwworm Outbreak Escalates in South Texas and New Mexico** (slug: `new-world-screwworm-outbreak-texas-new-mexico`) - A new note or an update to an existing note if there is one. Let's check our existing notes first to see if there is a note about the screwworm. I can use `read_notes` to see what notes exist on the topic. Let's do that!

Ah! I see that we do have an existing note on the screwworm: - `new-world-screwworm-us-outbreak` ("New World Screwworm Southwest Outbreak Triggers CDC Emergency Operations Center Activation", updated 2026-06-23). I can update this existing note using the slug `new-world-screwworm-us-outbreak` to capture the escalation to 31 cases, the emergency quarantines in Texas, and Representative Cuellar's criticism of the slow-moving Edinburg sterile fly facility. We also have: - `fda-regulatory-pivot-advisory-committees-capricor-replimune` ("The Post-Makary FDA Pivot: Reversals, Resubmissions, and a Return to Advisory Committees", updated 2026-07-02). I can update this note with the June 26 acceptance of Replimune's RP1 BLA resubmission, the late-July AdCom, and the Aug 2 PDUFA date, as well as Sobi's CRL on June 26 and the upcoming Capricor PDUFA date on Aug 22. We can write a brand-new note for: - **AbbVie's Skyrizi Pediatric FDA Approval**: `fda-approval-skyrizi-pediatric-psoriasis-arthritis` (or similar). This is a major first-in-class pediatric approval. - **FDA ISTAND In Silico Program**: `fda-istand-first-in-silico-drug-development-tool`. This is the first AI-driven digital liver model accepted under the ISTAND program. Let's double-check if there are other details we should search for to make these findings absolutely rock solid and grounded. Let's search for the exact details of the ISTAND tool (such as the developer and the tool's name). The FDA's press release says: - "The DDT is [an artificial intelligence (AI)-Driven Digital Liver Model for Prediction of Drug-Induced Liver Injury (DILI)](https://force-dsc.my.site.com/ddt/s/ddt-project?ddtprojectid=247)" Let's see if we can find the developer of this tool or more details about the tool itself. I'll search the web for `"AI-Driven Digital Liver Model" "ISTAND" 2026`.

Okay, the developer/sponsor of this tool is listed on the FDA's DDT project page as "DDT Project ID 247". Let's do a quick search to see what company or academic institution submitted it. It's often "DDT Project ID 247" or a specific company like "Simulations Plus", "DILIsym Services", or another AI developer. Let's run a search for `"DDT Project ID 247"` or `"DDT-247"`.

Ah! "Srijit Seal's Post - LinkedIn" says: "I'm very happy to see that the US FDA has officially mentioned our DILI..." Let's search for "Srijit Seal" and "DILI" or "liver model" to see who Srijit Seal is and what organization developed it. Usually, it's a researcher from a university or a specific lab. Let's do a quick search.

Excellent! The tool is **DILIPredictor** developed by Srijit Seal and collaborators (including Andreas Bender's group at the University of Cambridge, Uppsala University, and partners like AstraZeneca). The tool leverages AI/chemoinformatics to predict human Drug-Induced Liver Injury (DILI) by integrating chemical structures, predicted *in vivo* and *in vitro* data, and comparing them against historical reference drugs with known DILI risks (the FDA's DILIst dataset). It was accepted under the FDA's CDER ISTAND (Innovative Science and Technology Approaches for New Drugs) program as the first-ever *in silico* Drug Development Tool (DDT) to receive an accepted Letter of Intent (LOI). Let's check if there are other threads or watches we can update. Let's see: - `019ec32d-6d1a-725d-9d28-251b38e8d928` ("USDA $750M sterile screwworm fly facility operational launch in Texas") - We have verified that the facility is under construction at Moore Air Force Base in Edinburg, Texas, but is "not moving fast enough" and won't be ready until 2027. Meanwhile, the U.S. and Mexico have opened a new facility in southern Chiapas, Mexico, releasing 50 million sterile flies per week. We should record an event on this watch thread to reflect this update. Wait, let's see which specific thread ID corresponds to this watch. The thread ID is `019ec32d-6d1a-725d-9d28-251b38e8d928` (or we can look it up in the `list_threads` response: yes, ID is `019ec32d-6d1a-725d-9d28-251b38e8d928`). Let's record an event on this watch since it's an ongoing watch that has a major update, but set `resolves: false` as the Edinburg facility is still under construction and not yet launched. Let's call `record_event` for this watch.

Ah, my web_search budget is spent. That is completely fine because we have collected extremely rich, robust, and citable evidence for multiple findings. Let's review what notes we need to write/update: 1. **New World Screwworm Southwest Outbreak**: - Slug: `new-world-screwworm-us-outbreak` (This is the exact slug of our existing note). - We will update it to reflect the escalation of the outbreak to 31 confirmed cases (30 in Texas, 1 in New Mexico) as of July 3, 2026. - We will cite the Texas Public Radio and Border Report articles, including Representative Cuellar's comments about the Edinburg sterile fly facility and the new Chiapas facility. 2. **The Post-Makary FDA Pivot: Reversals, Resubmissions, and a Return to Advisory Committees**: - Slug: `fda-regulatory-pivot-advisory-committees-capricor-replimune` (This is the exact slug of our existing note). - We will update it to reflect the formal acceptance of Replimune's RP1 BLA resubmission on June 26, 2026, with an August 2, 2026 PDUFA date and a late-July AdCom. - We will also add the June 26 CRL for Sobi's NASP due to third-party manufacturing failures, and the upcoming Capricor deramiocel PDUFA date on August 22, 2026. 3. **FDA Accepts First In Silico Drug Development Tool Under ISTAND Program**: - Slug: `fda-istand-first-in-silico-drug-development-tool` (New note). - We will write a brand-new note about the FDA CDER accepting the first-ever LOI for an AI-driven digital liver model (**DILIPredictor**) to predict Drug-Induced Liver Injury (DILI) under the ISTAND program on June 3, 2026. 4. **FDA Approves AbbVie's Skyrizi for Pediatric Plaque Psoriasis and Psoriatic Arthritis**: - Slug: `fda-approval-skyrizi-pediatric-psoriasis-arthritis` (New note). - We will write a brand-new note about the June 26, 2026 FDA approval of Skyrizi (risankizumab-rzaa) for children 6 and older, making it the first and only IL-23 inhibitor approved for pediatric patients under 40 kg with plaque psoriasis or active psoriatic arthritis. Let's write these notes one by one. First, let's update `fda-regulatory-pivot-advisory-committees-capricor-replimune`. Let's read the prior note first if possible, or we can write the updated note which replaces it. Since we don't have the full body of the prior note, I will write a comprehensive, robust update that incorporates the new developments alongside the previous context (acting Commissioner Kyle Diamantas, the exit of Makary/Prasad, and the return of advisory committees for Capricor's deramiocel and Replimune's RP1, plus Sobi's CRL). Wait, let's write the note for `fda-regulatory-pivot-advisory-committees-capricor-replimune`. I will draft a high-quality, professional markdown note with no YAML frontmatter, starting with a `# ` header as instructed. I will name and link the actual sources and carry verbatim quotes. Let's do it!

Now let's update the existing note on the New World screwworm outbreak: `new-world-screwworm-us-outbreak`. We will write a comprehensive, updated note that captures the escalation of the outbreak to 31 cases, the emergency quarantines across 21 Texas counties, and Representative Henry Cuellar's criticism regarding the slow pace of construction for the $610 million sterile fly facility in Edinburg, Texas. Let's write it.

Now let's write the brand-new note for the FDA's ISTAND program accepting the first-ever *in silico* Drug Development Tool: `fda-istand-first-in-silico-drug-development-tool`. Let's draft it.

Now let's write the brand-new note for AbbVie's Skyrizi pediatric FDA approval: `fda-approval-skyrizi-pediatric-psoriasis-arthritis`. Let's draft it.

I have successfully written and updated all relevant findings for this cycle: 1. Updated `fda-regulatory-pivot-advisory-committees-capricor-replimune` to capture the formal acceptance of Replimune's RP1 BLA resubmission on June 26, 2026, the late-July AdCom, and Sobi's CRL on June 26. 2. Updated `new-world-screwworm-us-outbreak` to capture the escalation of the outbreak to 31 confirmed cases, emergency quarantines, and Rep. Cuellar's criticism of the Edinburg sterile fly facility delays. 3. Created `fda-istand-first-in-silico-drug-development-tool` to capture the FDA's historic acceptance of the first *in silico* (AI-driven) drug development tool, DILIPredictor, under the ISTAND program. 4. Created `fda-approval-skyrizi-pediatric-psoriasis-arthritis` to capture the landmark FDA approval of AbbVie's Skyrizi as the first IL-23 inhibitor for pediatric plaque psoriasis and active psoriatic arthritis. I will now call `finish_cycle` to complete this research cycle.

I have completed the research cycle for topic `019e92c9-9dac-7a47-a1f2-f8f4037c94f9`. ### Summary of Key Findings from this Cycle: 1. **The Post-Makary FDA Pivot ([[fda-regulatory-pivot-advisory-committees-capricor-replimune]])**: - **Replimune RP1 BLA Acceptance**: On June 26, 2026, Replimune announced that the FDA accepted its BLA resubmission for RP1 in advanced melanoma, setting a PDUFA date of August 2, 2026, and notifying the company of an upcoming late-July Advisory Committee meeting. - **Sobi's NASP CRL**: On June 26, 2026, Sobi received a Complete Response Letter from the FDA for its gout therapy NASP, citing third-party contract manufacturing deficiencies (with no safety/efficacy concerns raised). - **Capricor's Deramiocel**: Moving toward an August 22, 2026 PDUFA date, with an Advisory Committee meeting scheduled for July 29, 2026. 2. **New World Screwworm Outbreak Escalation ([[new-world-screwworm-us-outbreak]])**: - The Southwest outbreak has reached **31 confirmed infestations** (30 in Texas, 1 in New Mexico) as of July 3, 2026, prompting strict emergency quarantines across 21 Texas counties. - Representative Henry Cuellar criticized the slow progress of the USDA's **$610 million sterile fly production facility** in Edinburg, Texas, which is delayed until late 2027. (An event was recorded on watch `019ec32d-6d1a-725d-9d28-251b38e8d928` to track this timeline shift). 3. **FDA Accepts First In Silico Drug Development Tool under ISTAND ([[fda-istand-first-in-silico-drug-development-tool]])**: - On June 3, 2026, the FDA's CDER accepted the first-ever Letter of Intent (LOI) for an *in silico* (AI-driven) drug development tool under the ISTAND program. - The tool, **DILIPredictor**, is an AI-driven digital liver model designed to predict Drug-Induced Liver Injury (DILI) during preclinical phases, supporting the FDA's commitment to New Approach Methodologies (NAMs) and reducing animal testing. 4. **FDA Approves AbbVie's Skyrizi for Pediatric Use ([[fda-approval-skyrizi-pediatric-psoriasis-arthritis]])**: - On June 26, 2026, the FDA approved Skyrizi (risankizumab-rzaa) for children aged 6 and older with moderate-to-severe plaque psoriasis or active psoriatic arthritis. - This approval includes a new **55 mg pre-filled syringe** for patients under 40 kg, making Skyrizi the first and only IL-23 inhibitor approved in the U.S. for pediatric patients in this weight category.