$PRME One of the aspects I like most about Prime's platform is the modularity and how it positions them to capitalize on recent FDA efforts to streamline approvals and make bespoke genetic medicine more scalable.
Although prime editing can theoretically repair most genetic mutations, old FDA rules would treat every new guide RNA as a brand-new drug. Spending years and tens of millions of dollars repeating animal tox, biodistribution, and manufacturing validation for single point mutations left thousands of rare diseases commercially stranded.
In light of ongoing shifts at the FDA, Prime is well positioned to break through this bottleneck:
1) Turning Drug Development into an Interchangeable Process
Prime’s Universal Liver LNP packages five standardized chemical components around prime editor mRNA.
• To target a new liver mutation or disease, Prime leaves the entire nanoparticle shell, delivery formulation, and editor mRNA completely intact, swapping only the guide RNA sequences (less than 5% of the drug’s total mass).
• Under the FDA’s Platform Technology Designation and Leveraging Prior Knowledge frameworks, Prime could cross-reference safety, stability, and CMC data across programs. This is likely why PM647 (AATD) cleared its IND in September 2026 just weeks after PM577a (Wilson disease) in July, cutting preclinical time and capital expenditure with each successive pipeline asset.
2) "Umbrella" Approvals Across Mutational Families
In Wilson disease, Prime’s lead in vivo candidate (PM577a) targets the H1069Q mutation common in the West, while a follow-on candidate addresses the R778L variant prevalent in East Asia.
• Under the FDA’s draft Plausible Mechanism Framework, once PM577a demonstrates clinical proof-of-mechanism in the human liver, Prime could potentially bundle follow-on ATP7B guides into master protocols or supplemental filings without running multi-year, standalone trials for every variant.
• As CEO Dr. Allan Reine noted after dosing the first PM577a patient this month, the same shared LNP delivery approach provides a direct path to expand into global patient populations across mutational families.
3) De-Risked Human Biology & Near-Term Catalysts
Prime editing is no longer purely theoretical. In PM359 for p47phox CGD, Prime proved in humans (NEJM, Dec 2025) that prime editors repair DNA cleanly without double-stranded breaks, restoring functional neutrophil activity to 69–83% (well clear of the 20% clinical efficacy threshold).
• Holding RMAT and Rare Pediatric Disease designations, PM359 is on track for a streamlined 1H 2027 BLA under the FDA's Rare Disease Evidence Principles (RDEP), a milestone that could unlock a Priority Review Voucher (PRV) worth about $100M+ in non-dilutive capital.
• Upcoming 2027 clinical readouts for PM577a (Wilson) and PM647 (AATD) rely on direct, objective biomarkers (serum ceruloplasmin, 64Cu PET copper efflux, and functional M-AAT protein), insulating the platform from the subjective clinical-scale failures that tripped up others.
In short, the modular nature of Prime's platform combined with the FDA's regulatory updates could allow the tech to evolve from an unscalable trial-and-error grind into a plug-and-play platform, sharply lowering the cost and latency required to commercialize genetic cures.
$PRME Regulation can make or break a thesis in bio. Between 2024-2026, the FDA has been overhauling how it evaluates genetic medicines and platform technologies like Prime editing, creating a potential tailwind for this type of tech.
Roughly 95% of rare diseases still have no approved treatment. Instead of forcing ultra-rare programs into slow, legacy clinical trial models designed for mass-market pills, the FDA has announced several policy changes to modernize the process:
• Plug-and-Play Platform Reuse (May 2024 & Summer 2026)
Once a delivery vehicle or manufacturing method (like a standardized LNP or AAV vector) is approved, sponsors no longer have to start from scratch. Under Section 506K and recent genome-editing guidance, companies can cross-reference prior safety, biodistribution, and manufacturing (CMC) data across different drug candidates using the same platform.
• Single-Arm Approvals for Ultra-Rare Diseases (Sept 2025)
For severe genetic conditions affecting less than 1,000 U.S. patients, randomized placebo trials are practically impossible. Building on previous policy, the FDA’s Rare Disease Evidence Principles (RDEP) now permit full marketing approval based on a single-arm trial, provided it’s backed by clear natural history data and confirmatory biomarker readouts.
• Mutation Bundling via Draft "Plausible Mechanism" (Feb 2026)
Gene editing therapies often target distinct, patient-specific mutations within the exact same gene. Under the Plausible Mechanism Framework, sponsors could bundle multiple mutation-specific editors into a single trial and BLA under a master protocol. In addition, new mutation variants could potentially be added post-approval without requiring full-scale clinical trials.
• Restored Non-Dilutive Capital & Division-Wide Alignment (2026)
Congress and the White House reauthorized the Rare Pediatric Disease Priority Review Voucher (PRV) program, restoring an asset historically worth about $100M+ in cash upon approval. Capping this off, the FDA’s recent rare disease framework whitepaper standardizes Bayesian stats and flexible CMC inspections across all CDER and CBER review divisions to eliminate inconsistent standards.
In short, for modular genetic medicines with hard biomarker readouts, the FDA is starting to dismantle the traditional 10-year development gauntlet in favor of a faster, capital-efficient, plug-and-play framework. While some of these shifts are still in a draft or non-binding guidance status, they're shaping up to be a regulatory sweet spot for therapies like prime editing that directly repair a root genetic mutation and deliver objective, binary biochemical proof.
Eli Lilly CEO Dave Ricks says AI helping us conquer disease will require "lots and lots of data that doesn't exist, yet."
Why I continue to focus on companies that own properietary data (like AbCellera & Tempus) and companies that help generate new data at scale (like Twist).
ALT "Well said Vas. Al will help us conquer disease, but this will take time, effort and lots and lots of data that doesn't exist, yet. would add that robotic labs will begin to make scaling data more tractable." — Dave A Ricks | CEO of Eli Lilly
$TWST I find it odd that some are saying that there is no data bottleneck in AI x Bio, and others are saying it's already over...
Meanwhile, billions of dollars in investments (from Biohub, Meta, the DOE, the NIH, Google Deepmind, and others) were recently announced to generate the massive amounts of data needed to train biological AI models as part of the Virtual Biology Initiative.
Plus, Anthropic recently unveiled their wetlab in SF, launched a protein design competition, and seems to just be getting started with their push into bio.
On top of that, in a recent interview, Max Jaderberg, president of Isomorphic Labs (recently rumored to be raising a new round at $40B), said:
"In AI, if you don't feel limited by data or you don't feel limited by compute, you're doing something wrong. Especially in the space of biology in chemistry, you can't just go to the internet and download data here. There are some amazing historical data sets that have been created, but actually we believe that a lot of the data that's going to power this space needs to be generated specifically for the models."
Well connected companies with deep pockets run by smart people are commiting a lot of money toward generating massive amounts of data to train biological models in the coming years and even the government is getting involved.
It's real, and it's not over.
Despite the crazy price action, I continue to believe Twist is very well positioned for this theme, especially in light of biosecurity concerns, competition from China, and an increasing focus on domestic biomanufacturing.
Same. Although, I wouldn't mind if Twist and Adaptyv combined forces 😏
At this point, I'm wondering how @adaptyvbio hasn't already been acquired by @AnthropicAI!
$ABCL AbCellera’s official abstract for ABCL635 from The Menopause Society 2026 meeting is out.
While we already knew the high-level Phase 2 data, this new TMS abstract gives us a deeper look at a few more granular data points:
1) Exact Headache Breakdown (Clustered at the Highest Dose)
Prior slides noted mild headache as a common adverse event, but we now have the exact numbers. In the SAD cohort, transient, mild headache occurred in 23.3% (n=7) of participants within the first few days of dosing. Importantly, more than half of those cases (n=4) were clustered at the highest 900mg supratherapeutic dose, well above the 300mg and 600mg doses taken into the multi-dose cohort.
2) Quantified Target Engagement (65% to 80% Testosterone Drop)
In Q1 earnings slides, AbCellera showed line graphs of hormone suppression to prove ABCL635 was hitting the target. The abstract puts more hard numbers to those charts: male participants saw a 65% to 80% reduction in testosterone from baseline across the 300mg to 900mg doses (alongside corresponding drops in LH and FSH), confirming strong, concentration-dependent HPG axis suppression.
3) Cohort Demographics
The abstract also discloses the exact median ages for the trial groups: 54.5 years for the SAD cohort and 62.0 years for the MAD cohort.
Quick recap of the Phase 1/2 core results:
• Trial Setup: The Single Ascending Dose (SAD) cohort enrolled 40 healthy men and postmenopausal women (6:2 active-to-placebo across 30mg, 100mg, 300mg, 600mg, and 900mg). The Multiple Ascending Dose (MAD) cohort enrolled 16 healthy postmenopausal women (6:2 active-to-placebo receiving 3 monthly doses of 300mg or 600mg), alongside the Phase 2 proof-of-concept cohort in women with moderate-to-severe VMS.
• Clean Safety & Liver Profile: Zero serious or severe adverse events, no dose-limiting toxicities, and (crucially for the NK3R class) no clinically significant liver enzyme elevations across either the SAD or MAD cohorts.
• Validated Monthly Dosing (PK): Dose-proportional exposure with a roughly 24-day half-life, backing up the convenient once-every-4-weeks injection schedule.
To summarize, the granular numbers reinforce the bull case for ABCL635. We’re seeing potent, quantifiable target engagement at therapeutic doses, a roughly 24-day half-life that easily supports monthly dosing, and a very clean safety profile where even mild side effects like headaches were largely confined to the maxed-out 900mg test dose, all with zero liver toxicity signals.
$ABCL
🧬 ABCL635,
이제는 효능을 넘어 3상을 준비할 근거를 쌓고 있다.
TMS 2026 CLINICAL UPDATE
$ABCL의 이번 학회 초록에서 제가 주목하는 것은 단순한 안면홍조 개선 효과가 아닙니다.
약 24일의 반감기, 반복 투여 안전성, 실제 표적 작용 확인까지. ABCL635이 월 1회 투여하는 항체 치료제로 개발될 수 있는 근거가 축적되고 있다는 점입니다.
1. 반복 투여에서도 긍정적인 초기 안전성
임상 1상에서 단회 투여 40명, 반복 투여 16명을 평가했습니다.
반복 투여군은 300mg 또는 600mg을 4주 간격으로 총 3회 투여받았습니다.
현재 초록에 보고된 결과는 다음과 같습니다.
* 중대한 이상반응 없음
* 중증 이상반응 없음
* 용량 제한 독성 없음
* 임상적으로 유의미한 간기능 수치 상승 없음7
다만 경미하고 일시적인 두통은 관찰됐으며, 더 큰 임상시험에서 안전성을 검증해야 합니다.
2. 반감기 약 24일, 월 1회 주사 가능성
약동학(PK) 분석에서 약 24일의 말기 반감기가 확인됐습니다.
이는 회사가 목표로 하는 월 1회 피하주사 전략을 뒷받침합니다.
또한 약력학(PD) 분석에서는 NK3R 관련 신호 경로에 실제로 작용한다는 근거가 확인됐습니다.
다만 반감기 24일이 곧 4주 내내 동일한 치료 효과를 보장하는 것은 아닙니다.
3. 기존 임상 2상 효능과 연결해 보면
ABCL635은 이미 임상 2상 4주 차에서 다음 결과를 발표했습니다.
중등도~중증 안면홍조 빈도 83% 감소
위약군은 33% 감소
위약 대비 하루 5.3회 추가 감소
37%는 안면홍조가 완전히 소실
이번 초록은 이러한 효능을 뒷받침할 약물 특성과 초기 안전성 근거를 보여준다는 데 의미가 있습니다.
4. 10월 22일 TMS 학회에서 확인할 것
이번 초록 자체에는 우리가 기다리는 완전한 12주 효능 지속성 데이터가 포함돼 있지 않습니다.
회사는 TMS 포스터에서 임상 1상 반복 용량 증량 시험의 새로운 안전성 자료와 임상 2상의 새로운 환자 보고 결과를 제시할 예정이라고 밝혔습니다.
우리가 확인할 핵심은 세 가지입니다.
① 반복 투여 시 안전성 결과의 구체적인 내용
② 환자들이 실제로 체감한 증상 및 삶의 질 개선
③ 새로운 자료가 향후 투여 용량과 3상 설계에 제공하는 근거
5. 다음 단계는 12주 데이터와 임상 3상
제가 가장 중요하게 생각하는 것은 앞으로 공개될 12주 데이터입니다.
초기 효능이 얼마나 지속되는지, 약물 농도가 감소하면서 효과는 어떻게 변화하는지, 최적의 투여 용량과 간격은 무엇인지 확인해야 합니다.
이러한 결과가 긍정적이라면 ABCL635은 임상 3상 설계의 불확실성을 한 단계 더 줄일 수 있습니다.
그러나 3상 개시와 성공, 상용화는 아직 확정된 결과가 아닙니다.
💬 마지막 코멘트
ABCL635은 이제 단순히 효능이 강한 후보물질인지 평가하는 단계를 넘어, 실제로 반복 투여할 수 있는 의약품으로 발전할 수 있는지를 검증하고 있습니다.
10월 22일 TMS 발표, 이후 12주 데이터, 그리고 2027년을 목표로 준비 중인 후기 임상 개발.
저는 이 과정이 ABCL635의 가치뿐 아니라 AbCellera가 자체적으로 신약을 개발할 수 있는 기업인지 판단하는 중요한 시험대가 될 것으로 봅니다.
좋은 항체를 발견하는 능력에서, 좋은 의약품을 완성하는 능력으로.
🔗 참고자료 / PRIMARY SOURCES
The Menopause Society — TMS 2026 Abstract P-92
menopause.org/
Jack Prescott — ABCL635 학회 초록
xitter.cf/JackPrescottX/status/2…
AbCellera — ABCL635 공식 파이프라인
abcellera.com/pipeline/abcl6…
AbCellera — TMS 2026 발표 안내
xitter.cf/AbCelleraBio/status/21…
$TWST More collaboration between Twist and Anthropic: "Teams at Adaptyv Bio and Twist Bioscience experimentally tested 211 designs for binding."
Plus, Citrini launches Citrini Therapeutics 👀
🦂 This was a very fun collaboration with the team @citrini! Thank you to @TwistBioscience and @adaptyvbio for the rapid turnaround on experimental validation and to Susana Vázquez Torres (@CNIOStopCancer), Tim Jenkins (@DTUtweet ), and Dan Bedinger (@carterra_bio) for their thoughtful review.
Read more in our blog post: anthropic.com/research/claud…
Brandon Richard retweeted
As psychedelic treatments approach potential FDA approval, psychiatrists need to be ready for patients’ questions.
To help prepare them, Johns Hopkins, Yale, NYU, and Columbia developed a standardized psychedelic medicine curriculum for psychiatry trainees. The first multi-site evaluation of the course was just published in Academic Psychiatry.
After the course:
💡 Confidence counseling patients about clinical research and legal care nearly doubled
🔬 Understanding of the limitations of current evidence rose sharply
📈 Knowledge quiz scores improved
⚖️ Trainees gained a more balanced, critically informed view of the evidence, without inflated enthusiasm for the field
We’re continuing to develop educational and training programs for professionals across a range of fields, so stay tuned!
doi.org/10.1007/s40596-026-0…
$TEM Tempus presented new clinical validation data at ESMO 2026 for an AI-enabled pre-screening panel in advanced non-small cell lung cancer (NSCLC), developed through its ongoing collaboration with Pfizer.
As the number of targeted therapies for lung cancer grows, identifying the right biomarkers requires running multiple, time-consuming tests on limited biopsy tissue. In practice, tumor tissue often runs out before testing is finished, forcing patients to go through invasive repeat biopsies or delaying targeted treatment.
Tempus is addressing this diagnostic bottleneck by pulling molecular signals directly from standard hematoxylin and eosin (H&E) digital pathology slides that are already generated during routine care.
Key takeaways:
• Massive Real-World Validation: The multi-center analysis evaluated 60,459 advanced NSCLC cases across 56,969 patients using routine whole-slide pathology images.
• High Analytical Sensitivity: The AI panel achieved more than 80% sensitivity across all 12 evaluated genomic and IHC biomarkers, with sensitivity exceeding 90% for several specific targets.
• Intelligent Diagnostic Triage: Still in development, the panel isn't meant to replace established sequencing (NGS) or immunohistochemistry (IHC) assays. Instead, it acts as a triage tool to help clinicians prioritize which confirmatory tests to order first, preserving limited tissue samples and getting patients on targeted therapies faster.
• Pharma Alignment: Conducting the study with Pfizer highlights a clear shared incentive. Pharma companies want to remove testing hurdles so more eligible patients actually get identified for precision therapies.
• Expanding the Digital Pathology Suite: This builds directly on Tempus’s existing AI biomarker work, sitting alongside Paige Predict (which analyzes H&E slides to predict 123 biomarkers across multiple cancer types when tissue is insufficient for sequencing) and Tempus Preview (which provides early biomarker predictions about 24 hours after a sample arrives at the lab).
In short, Tempus is using its multimodal data library to turn a routine pathology slide into an automated triage tool, helping doctors conserve tissue, eliminate testing delays, and route patients toward personalized treatments much faster.
ALT Tempus Presents Data Demonstrating AI-Enabled Pre-Screening Can Help Identify Patients for Biomarker Testing in NSCLC October 19, 2026 Study presented at ESMO evaluated more than 60,000 advanced NSCLC cases and found greater than 80% sensitivity across all 12 biomarkers using routine H&E pathology images. $TEM
Study presented at #ESMO26, from our collaboration with @pfizer, evaluated more than 60,000 advanced #NSCLC cases and found greater than 80% sensitivity across all 12 biomarkers using routine H&E pathology images.
Read on: tempus.co/4jpwO4X
$PRME Regulation can make or break a thesis in bio. Between 2024-2026, the FDA has been overhauling how it evaluates genetic medicines and platform technologies like Prime editing, creating a potential tailwind for this type of tech.
Roughly 95% of rare diseases still have no approved treatment. Instead of forcing ultra-rare programs into slow, legacy clinical trial models designed for mass-market pills, the FDA has announced several policy changes to modernize the process:
• Plug-and-Play Platform Reuse (May 2024 & Summer 2026)
Once a delivery vehicle or manufacturing method (like a standardized LNP or AAV vector) is approved, sponsors no longer have to start from scratch. Under Section 506K and recent genome-editing guidance, companies can cross-reference prior safety, biodistribution, and manufacturing (CMC) data across different drug candidates using the same platform.
• Single-Arm Approvals for Ultra-Rare Diseases (Sept 2025)
For severe genetic conditions affecting less than 1,000 U.S. patients, randomized placebo trials are practically impossible. Building on previous policy, the FDA’s Rare Disease Evidence Principles (RDEP) now permit full marketing approval based on a single-arm trial, provided it’s backed by clear natural history data and confirmatory biomarker readouts.
• Mutation Bundling via Draft "Plausible Mechanism" (Feb 2026)
Gene editing therapies often target distinct, patient-specific mutations within the exact same gene. Under the Plausible Mechanism Framework, sponsors could bundle multiple mutation-specific editors into a single trial and BLA under a master protocol. In addition, new mutation variants could potentially be added post-approval without requiring full-scale clinical trials.
• Restored Non-Dilutive Capital & Division-Wide Alignment (2026)
Congress and the White House reauthorized the Rare Pediatric Disease Priority Review Voucher (PRV) program, restoring an asset historically worth about $100M+ in cash upon approval. Capping this off, the FDA’s recent rare disease framework whitepaper standardizes Bayesian stats and flexible CMC inspections across all CDER and CBER review divisions to eliminate inconsistent standards.
In short, for modular genetic medicines with hard biomarker readouts, the FDA is starting to dismantle the traditional 10-year development gauntlet in favor of a faster, capital-efficient, plug-and-play framework. While some of these shifts are still in a draft or non-binding guidance status, they're shaping up to be a regulatory sweet spot for therapies like prime editing that directly repair a root genetic mutation and deliver objective, binary biochemical proof.
$PRME The FDA's new Rare Disease Framework Initiative is well-timed for Prime, especially considering their $108.8M in cash as of Q2 (runway into 2027).
Roughly 30M Americans have a rare disease ($997B annual burden), yet only about 5% have an approved therapy. Historically, the FDA’s 18+ rare disease programs were applied unevenly across review divisions (for example, the FDA rejecting uniQure’s plan to file a single-arm BLA in Huntington’s and mandating a sham-surgery trial).
The new framework aims to fix this division-by-division inconsistency by calibrating evidence and manufacturing rules to what is realistically attainable in small populations. This initiative caps a 13-month wave of CBER and CDER reforms to make regulatory flexibility the default norm.
Here are 4 ways the FDA's 2025–2026 rare disease overhaul could directly impact Prime:
1) De-Risking PM359's 1H 2027 BLA
While seeking a CGD partner to focus capital on in vivo liver programs, Prime is advancing PM359 (granted RMAT in June) toward a 1H 2027 BLA on Phase 1/2 data.
Unlike Huntington's (which has about 40,000 U.S. patients), p47phox CGD affects fewer than 1,000 U.S. patients and has a clear biochemical readout in functional neutrophil activity (exceeding 20% restores immune function, and PM359 hit 69–83% in NEJM). This checks every box of the FDA's Rare Disease Evidence Principles (RDEP) criteria for a single-arm filing.
2) Removing CMC Bottlenecks & Unlocking a $100M+ PRV
Historically, ex vivo stem cell therapies have been delayed by manufacturing (CMC) hurdles rather than clinical efficacy. Pairing the framework's risk-based CMC rules with CBER's Jan 2026 policy (dropping the 3-PPQ-lot mandate and allowing concurrent batch release and post-approval spec tweaks) could sharply cut the time and cost to make PM359 BLA-ready.
With Rare Pediatric Disease status (recently extended by Congress through 2029), approval also unlocks a Priority Review Voucher (PRV) worth $100M–150M+ in non-dilutive cash.
3) Scaling the "Universal Liver LNP" Platform
PM577a (Wilson disease, H1069Q), its R778L follow-on, and PM647 (AATD, PiZ) share the same GalNAc Universal Liver LNP and Prime Editor mRNA, swapping only the guide RNAs (pegRNA/ngRNA). Two 2026 FDA policies turn this modularity into a major moat:
• Platform Data Reuse (June 2026 Guidance): Safety, biodistribution, and CMC data from PM577a (first patient dosed Oct 5) can be reused across programs (evidenced by PM647 clearing its IND on Sept 24, just two months after PM577a).
• Mutation Bundling (Feb 2026 Plausible Mechanism Framework): Editors targeting different mutations in the same gene (like Wilson's ATP7B variants or Cystic Fibrosis CFTR variants) can be tested under one master protocol, bundled into a single BLA, and expanded to rarer variants.
4) Fast-Tracking 2027 Liver Readouts via Biomarkers
Instead of waiting 5–10 years for clinical cirrhosis or emphysema outcomes, the framework supports accelerated registration using direct mechanistic biomarkers:
• PM577a (Wilson): Measuring how effectively the liver clears copper into bile (via 64Cu PET imaging), blood ceruloplasmin (copper-carrying protein) levels, 24-hr urinary copper, and chelator withdrawal.
• PM647 (AATD): Restoring normal M-AAT protein levels and reducing toxic Z-AAT protein accumulation.
In short, the FDA is systematically removing the biggest historical roadblocks in gene editing for rare diseases, giving Prime a faster, clearer, and more capital-efficient path to validate its platform and monetize its pipeline.
Brandon Richard retweeted
We will report financial results for the third quarter ended September 30, 2026, before U.S. markets open on Monday, November 2, 2026.
The live audio webcast will be accessible through the “Events” section of the Tempus Investor Relations website, as well as here: tempus.co/47USb73
$ABCL Thad Hughes no longer works at AbCellera but it's interesting to see the background and experience of someone who helped build their AI/ML capabilities. Formerly worked at Google and his work at AbCellera led to a patent.
Presentation from 2021: youtu.be/9v38lwvlsgc?is=eucf…
Brandon Richard retweeted
Visit our poster at The Menopause Society 2026 Annual Meeting. We will be presenting Phase 1/2 results on ABCL635, an investigational, potential best-in-class antibody drug for the non-hormonal treatment of vasomotor symptoms.
Read more about ABCL635 here:
abcellera.com/pipeline/abcl6…
$TWST New Twist interview, always enjoy hearing Patrick Finn talk. Here, he explains how Twist acts as the physical wet-lab engine for generative biology with applications ranging from AI-driven discovery to MRD. Key highlights:
• Silicon Scale: By writing DNA on silicon chips rather than legacy plastic plates, Twist writes roughly 32 Million oligonucleotides a day with capacity for about 3 million clonal genes a year. That parallel throughput is what makes rapid design-build-test-learn iterations viable.
• Closing the Manufacturability Gap: AI models spit out highly engineered designs with inverted repeats, homopolymers, and extreme GC content that traditional synthesis struggles with. Twist’s complex gene platform raised sequence acceptance from 96% to 99.5%, delivering difficult designs in 12 to 15 days at industrial scale.
• Pure Infrastructure Player: Twist acts as a dedicated wet-lab execution layer, not a model builder. They don't take customer screening data to train competing proprietary drug discovery models, protecting partner IP.
• Halving Liquid Biopsy Sequencing Costs: Detecting rare ctDNA signals in tumor-informed MRD (minimal residual disease) requires massive sequencing depth (often 50,000x). Twist’s uniform target enrichment panels prevent wasted reads on off-target regions, cutting total sequencing costs for diagnostic partners by up to 50%.
• Pooled Testing at Scale (The MSK Case Study): When Memorial Sloan Kettering submitted 100,000 AI-designed antibodies, Twist synthesized the entire library as a single pool on a chip, ran display selections, and sequenced the binders. Real biological data goes directly back to train the next iteration of the model.
• The Bottleneck is Moving Downstream: AI removed the design constraint, and silicon synthesis is removing the build constraint. The bottleneck is now sliding downstream toward functional characterization, complex multi-specific formats, and chemistry manufacturing and controls (CMC).
Hear it straight from the source! Twist President & COO @genesynthesizer joins Ross Katz on the Data in Biotech Podcast to discuss antibody and AI drug discovery, liquid biopsy, MRD & Complex Genes: m.youtube.com/watch?v=mLwu8T…
@TwistBioscience
$PRME The FDA's new Rare Disease Framework Initiative is well-timed for Prime, especially considering their $108.8M in cash as of Q2 (runway into 2027).
Roughly 30M Americans have a rare disease ($997B annual burden), yet only about 5% have an approved therapy. Historically, the FDA’s 18+ rare disease programs were applied unevenly across review divisions (for example, the FDA rejecting uniQure’s plan to file a single-arm BLA in Huntington’s and mandating a sham-surgery trial).
The new framework aims to fix this division-by-division inconsistency by calibrating evidence and manufacturing rules to what is realistically attainable in small populations. This initiative caps a 13-month wave of CBER and CDER reforms to make regulatory flexibility the default norm.
Here are 4 ways the FDA's 2025–2026 rare disease overhaul could directly impact Prime:
1) De-Risking PM359's 1H 2027 BLA
While seeking a CGD partner to focus capital on in vivo liver programs, Prime is advancing PM359 (granted RMAT in June) toward a 1H 2027 BLA on Phase 1/2 data.
Unlike Huntington's (which has about 40,000 U.S. patients), p47phox CGD affects fewer than 1,000 U.S. patients and has a clear biochemical readout in functional neutrophil activity (exceeding 20% restores immune function, and PM359 hit 69–83% in NEJM). This checks every box of the FDA's Rare Disease Evidence Principles (RDEP) criteria for a single-arm filing.
2) Removing CMC Bottlenecks & Unlocking a $100M+ PRV
Historically, ex vivo stem cell therapies have been delayed by manufacturing (CMC) hurdles rather than clinical efficacy. Pairing the framework's risk-based CMC rules with CBER's Jan 2026 policy (dropping the 3-PPQ-lot mandate and allowing concurrent batch release and post-approval spec tweaks) could sharply cut the time and cost to make PM359 BLA-ready.
With Rare Pediatric Disease status (recently extended by Congress through 2029), approval also unlocks a Priority Review Voucher (PRV) worth $100M–150M+ in non-dilutive cash.
3) Scaling the "Universal Liver LNP" Platform
PM577a (Wilson disease, H1069Q), its R778L follow-on, and PM647 (AATD, PiZ) share the same GalNAc Universal Liver LNP and Prime Editor mRNA, swapping only the guide RNAs (pegRNA/ngRNA). Two 2026 FDA policies turn this modularity into a major moat:
• Platform Data Reuse (June 2026 Guidance): Safety, biodistribution, and CMC data from PM577a (first patient dosed Oct 5) can be reused across programs (evidenced by PM647 clearing its IND on Sept 24, just two months after PM577a).
• Mutation Bundling (Feb 2026 Plausible Mechanism Framework): Editors targeting different mutations in the same gene (like Wilson's ATP7B variants or Cystic Fibrosis CFTR variants) can be tested under one master protocol, bundled into a single BLA, and expanded to rarer variants.
4) Fast-Tracking 2027 Liver Readouts via Biomarkers
Instead of waiting 5–10 years for clinical cirrhosis or emphysema outcomes, the framework supports accelerated registration using direct mechanistic biomarkers:
• PM577a (Wilson): Measuring how effectively the liver clears copper into bile (via 64Cu PET imaging), blood ceruloplasmin (copper-carrying protein) levels, 24-hr urinary copper, and chelator withdrawal.
• PM647 (AATD): Restoring normal M-AAT protein levels and reducing toxic Z-AAT protein accumulation.
In short, the FDA is systematically removing the biggest historical roadblocks in gene editing for rare diseases, giving Prime a faster, clearer, and more capital-efficient path to validate its platform and monetize its pipeline.
The FDA today launched the Rare Disease Framework Initiative to reimagine rare disease drug development.
The new framework will adapt aspects of the agency’s long-standing approach designed for larger diseases. It will adopt an optimized, fit-for-purpose framework for rare disease drug development that considers the nuances of a specific disease, patient needs, product type, and attainable evidence. fda.gov/news-events/press-an…
FDA will host a meeting on Oct. 28 at the White Oak campus to collect feedback on the Rare Disease Framework Initiative from patients, disease advocates, industry, and other stakeholders. fda.gov/news-events/fda-meet…
Brandon Richard retweeted
I'm a simple man: 70% to 80% of rare disease are genetic, that's the lions share right there. In the original 2019 $PRME editing paper the authors calculated that prime editing can, in principle, correct up to ~89% of the ~75,000 known pathogenic human genetic variants in ClinVar. (Haven't found a clean number for base editing but probably around 30% to 60%)... Ofc delivery is an unsolved problem and I'm not saying that they can cure any single one of them. What I'm saying is that $BEAM & $PRME are the only ones who have a ball to shoot! Only thing that limits them is cash.
This is a meaningful step to bring better coordination around FDA initiatives to make the process for developing treatments for rare diseases more efficient. Will help accelerate new policy development.
bloomberg.com/news/articles/…
Brandon Richard retweeted
Base editing and prime editing clinical trial landscape, including today’s GSD type I clinical readout from @BeamTx.
