Lucid Diligence Brief: Regeneron and Tessera team on TSRA-196 for AATD

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Dive deeper

Seven questions, 60-second thesis frame.

What changed, and when

Regeneron and Tessera team on TSRA-196 for AATD with partnership announced on 01 Dec 2025. The global collaboration aims to co-develop and co-commercialise TSRA-196 for alpha-1 antitrypsin deficiency, with $150 million upfront including equity, 50:50 cost and profit share, and up to $125 million in near- and mid-term milestones, plus IND and multiple CTA filings targeted by year-end 2025. (Tessera press release) Independent coverage confirms the structure and timing, with several outlets framing the total headline value at $275 million. (Fierce Biotech, BioPharma Dive, FT markets summary of GlobeNewswire)

60-second thesis frame

TSRA-196 aims to correct SERPINA1 mutations in vivo via Tessera’s RNA Gene Writing and non-viral LNP delivery, positioning as a one-time therapy that could address both lung and liver disease in AATD, where current care is lifelong augmentation and liver transplant for severe hepatic disease. (Tessera press release, FDA patient-focused AATD document) De-risking signals include NHP and mouse data showing efficient SERPINA1 editing and favorable specificity, and a clear regulatory plan to file IND and CTAs in 2025. (Tessera NHP data, Jun 20, 2024, Tessera press release) Competitive bar is rising as Beam’s BEAM-302 has early clinical proof-of-concept in AATD, while Intellia discontinued its NTLA-3001 AATD program in Jan 2025, sharpening focus on modality and outcome benchmarks. (Beam PR, Mar 10, 2025, BioPharma Dive on Intellia discontinuation) Payer calculus will hinge on one-time value versus high annual costs of augmentation, and durability plus hepatic benefit claims. (Alpha-1 Foundation statement to FDA)

The seven diligence questions

Clinical

• What on-target editing rate, Z-AAT reduction, and functional M-AAT restoration thresholds will define success in first-in-human dosing, and how will durability be measured over 12–24 months, including hepatic histology or MRI-PDFF where relevant?
• Does non-viral LNP delivery plus RNA Gene Writer maintain high liver specificity and low off-target signals in humans consistent with NHP, and what is the immunogenicity management plan for repeat dosing if needed? (Tessera NHP data, Jun 20, 2024)

Payer or Access

• What real-world comparator and value narrative will be used against lifelong augmentation therapy and its costs, and can TSRA-196 credibly claim liver benefit that augmentation lacks? (Alpha-1 Foundation to FDA, FDA Prolastin resources)
• Will early coding and payment pathways be pursued, and how will coverage address genotype restrictions and long-term safety monitoring typical for in vivo gene editing?

Ops or Adoption

• What is the site-readiness plan for infusion, hepatic monitoring, and longitudinal labs, and can supply of clinical-grade LNP and mRNA scale for expansion cohorts without CMC delays?

Competitive

• How will TSRA-196 differentiate versus BEAM-302’s emerging clinical profile on AAT restoration, Z-AAT reduction, safety, and durability, and what bar would trigger program reprioritisation? (Beam PR, Mar 10, 2025)

Team or Cap table

• Are governance, profit-share, and global rights clear if the program expands to adjacent genotypes or extrahepatic manifestations, and are there closing conditions such as HSR that could push timelines? (Tessera press release notes HSR condition, FTC HSR guide, 30-day waiting period)

Red flags

• IND and CTA filings slip past Dec 2025 or trigger a clinical hold due to preclinical package gaps or CMC questions. (Tessera press release)
• Early human safety signals in liver enzymes, immunogenicity, or unintended edits that diverge from NHP and mouse data. (Tessera NHP data)
• Competitor data materially outperforms on AAT restoration and Z-AAT reduction, resetting regulator and payer expectations. (Beam PR)

Next catalyst

HSR waiting-period milestone after filings, then IND and initial CTAs targeted by Dec 2025, with potential IND clearance in early 2026 subject to FDA review. (Tessera press release, FTC HSR overview)

FAQ

• What exactly changed by Regeneron and Tessera’s announcement on 01 Dec 2025 to jointly develop TSRA-196, and why does it matter for AATD?
  They formed a global 50:50 collaboration for TSRA-196, with $150 million upfront and equity to Tessera, up to $125 million in additional milestones, and plans to file IND and CTAs by end-2025, aiming at a one-time corrective therapy for AATD. (Tessera press release, Fierce Biotech, BioPharma Dive)
• What is the regulatory path after the 01 Dec 2025 announcement by Regeneron and Tessera, and what are next formal steps in the US, UK, and EU?
  The parties cite IND and multiple CTAs by Dec 2025, followed by standard agency review windows, and the deal itself is subject to HSR pre-merger clearance in the US. (Tessera press release, FTC HSR guide)
• Which endpoints are likely in the first TSRA-196 study by Tessera and Regeneron, and how meaningful would they be?
  Early endpoints will likely include safety, pharmacodynamics, Z-AAT reduction, and restoration of functional AAT, mirroring competitor design logic and registry precedents. A posted study record for TSRA-196 exists on ClinicalTrials.gov, indicating PiZZ adult enrollment and genetic inclusion criteria. (ClinicalTrials.gov NCT07227207)
• What safety issues matter post-Regeneron’s and Tessera’s announcement, and could they change real-world use?
  In vivo editing in the liver requires close monitoring of transaminases, off-target edits, and immunogenicity. Prior NHP data for TSRA-196 reported high liver specificity and no germline or off-target editing, but translation to humans remains to be proven. (Tessera NHP data)
• How might major US payers view access after Regeneron’s and Tessera’s news on 01 Dec 2025, given augmentation as current care and coding needs for a one-time therapy?
  Payers will weigh one-time cost against lifelong augmentation and its limitations, including lack of liver benefit, and will expect robust durability data and post-treatment monitoring plans before broad coverage. (Alpha-1 Foundation statement to FDA, FDA Prolastin resources)

Publisher / Disclosure

Publisher: LucidQuest Ventures Ltd. Produced: 02 Dec 2025, 10:00 London. Purpose: general and impersonal information. Not investment research or advice, no offer or solicitation, no suitability assessment. UK: directed at investment professionals under Article 19(5) and certain high-net-worth entities under Article 49(2)(a)–(d) of the Financial Promotion Order 2005. Others should not act on this. Sources and accuracy: public sources believed reliable, provided “as is,” may change without notice. No duty to update. Past performance is not reliable. Forward-looking statements carry risks. Methodology: questions-first framework using public sources. No conflicts. Authors do not hold positions unless stated. © 2025 LucidQuest Ventures Ltd.

Entities / Keywords

Regeneron; Tessera Therapeutics; TSRA-196; Gene Writing; RNA Gene Writer; non-viral LNP; SERPINA1; AATD; alpha-1 antitrypsin; Z-AAT; M-AAT; IND; CTA; HSR; FDA; EMA; MHRA; ClinicalTrials.gov NCT07227207; NHP data; ASGCT; FASEB; augmentation therapy; Prolastin-C; Beam Therapeutics; BEAM-302; base editing; Intellia Therapeutics; NTLA-3001; BioPharma Dive; Fierce Biotech; FT GlobeNewswire; payer access; durability; off-target; immunogenicity; liver specificity; first-in-human; profit share 50–50; $150 million upfront; $125 million milestones

 

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