What changed, and when

Vyriad closed the final $25 million tranche of its Series B on 23 Dec 2025, taking the round to $85 million and guiding first-in-human testing of VV169 in relapsed or treatment-refractory multiple myeloma in 2026 (Vyriad press release). Independent carry and trade outlets echoed the terms and clinical intent (Business Wire, BioWorld brief, Yahoo Finance).

60-second thesis frame

Signal is timely, funding is founder-led, and modality momentum is real. Vyriad is pushing an in-vivo CAR-T, VV169, using a retargeted lentiviral vector, LV-169, to transduce T cells in situ and generate BCMA CAR-T cells with a single IV dose, aiming to skip apheresis, ex-vivo manufacturing, and lymphodepletion (Vyriad ASH 2025 data note). Preclinical ASH posters reported complete tumor clearance in mice and muted inflammatory cytokines, supporting IND-enablement for a 2026 start (Vyriad ASH 2025 data note). Platform credibility is helped by a 2024 Novartis in-vivo CAR-T collaboration (Vyriad–Novartis collaboration, Fierce Biotech coverage). Field validation is emerging from peers with early human data in multiple myeloma, but human translation, immunogenicity, and payer classification for in-vivo delivery remain the main execution risks (Kelonia ASH 2025 release, Reuters on Interius deal).

The seven diligence questions

Clinical

• Does VV169 achieve reliable in-vivo T-cell transduction and expansion in first-in-human MM without lymphodepletion, and what dose window balances potency with cytokine safety seen preclinically (Vyriad ASH 2025 data note)?
• How does persistence compare with ex-vivo BCMA CAR-Ts, and can re-dosing be done safely if transgene immunity arises (context from peers’ early human readouts, Kelonia KLN-1010) (Kelonia ASH 2025 release)?

Payer or Access

• How will Medicare and commercial payers classify and pay for an in-vivo CAR-T product, given current CAR-T coverage under NCD 110.24 and MS-DRG 018 for inpatient claims (CMS NCD 110.24, CGS MS-DRG 018 guidance)?
• If VV169 avoids apheresis and cell processing, do payers expect lower total episode costs or create new site-of-care rules for gene therapy-like products, and will unique HCPCS or crosswalks be required initially (ASTCT coding options, Apr 2025)?

Ops or Adoption

• Can Vyriad manufacture LV-169 at commercial scale with serum-stable, T-cell-targeted envelopes while keeping COGS and release testing timelines favorable to outpatient delivery (Vyriad in-vivo platform overview)?

Competitive

• How differentiated is VV169 versus other in-vivo CAR-T approaches in MM and autoimmune, and what is the durable access moat as peers advance clinical programs and M&A accelerates (Kelonia first-in-human, Gilead/Kite–Interius acquisition, BMS–Orbital acquisition) (Kelonia ASH 2025 release, Reuters on Interius, BMS press release on Orbital)?

Team or Cap table

• Does founder-led governance and the Stine-backed Series B syndicate provide runway and discipline through first-in-human milestones, and how do Novartis and Regeneron partnerships shape capital needs (Vyriad 23 Dec 2025 PR, 2022 Series B investor roster, Vyriad–Novartis collaboration)?

Red flags

• Human translation risk from mouse to first-in-human, including vector immunogenicity, off-target transduction, and insertional mutagenesis, despite encouraging cytokine profiles in preclinical data (Vyriad ASH 2025 data note).
• Reimbursement ambiguity for in-vivo delivery that does not map neatly to existing CAR-T autologous codes and MS-DRG pricing frameworks in early commercialization (CMS NCD 110.24, ASTCT coding options).
• Competitive overhang as multiple in-vivo CAR-T entrants show early human signals and trigger strategic M&A that can compress differentiation windows (Kelonia ASH 2025 release, Reuters on Interius).

Next catalyst

Planned U.S. IND clearance and Phase 1 first-patient-in for VV169 in 2026, with formal trial listing expected on ClinicalTrials.gov, per company guidance (Vyriad 23 Dec 2025 PR, Vyriad ASH 2025 data note).

FAQ

• What exactly changed by Vyriad’s “final $25M Series B” news on 23 Dec 2025, and why does it matter for multiple myeloma?
  Vyriad completed its Series B at $85 million to support first-in-human testing of VV169, an in-vivo BCMA CAR-T candidate for relapsed or treatment-refractory multiple myeloma in 2026 (Vyriad press release, Business Wire).
• What is the regulatory path after Vyriad’s news on its $25M Series B and what are the next formal steps in the US, UK, and EU?
  The company guides to a 2026 U.S. first-in-human start, implying IND submission, FDA safe-to-proceed, and subsequent trial registration, then analogous clinical trial authorizations in the UK and EU for expansion if pursued (Vyriad ASH 2025 data note). Medicare’s existing CAR-T NCD provides a template for U.S. trial coverage while coding pathways for in-vivo products evolve (CMS NCD 110.24).
• Which endpoints or data underpinned the momentum cited in Vyriad’s announcement of $25M Series B on 23 Dec 2025?
  At ASH 2025 Vyriad reported 100 percent tumor clearance in murine MM models after a single VV169 infusion, with low inflammatory cytokines and resistance to re-challenge, supporting clinical translation (Vyriad ASH 2025 data note). Peers have begun showing human signals in MM, increasing confidence that in-vivo CAR-T can be clinically active (Kelonia ASH 2025 release).
• How does VV169 differ mechanically from approved therapies like Carvykti or Abecma?
  Approved therapies are ex vivo, requiring patient T-cells to be extracted, modified in a lab, and reinfused weeks later. VV169 is an off-the-shelf lentiviral vector injected intravenously that seeks out and modifies T-cells directly within the patient’s bloodstream (Beacon Blog, FirstWord Pharma).
• What role do Regeneron and Novartis play in Vyriad’s current strategy?
  Regeneron is a long-term investor and partner on oncolytic viruses, while Novartis signed a collaboration in Nov 2024 specifically to develop in vivo CAR-T assets using Vyriad’s vector platform. These partnerships validate the underlying delivery technology and provide non-dilutive capital (Vyriad partnerships, Fierce Biotech).
• How will major U.S. payers treat access after Vyriad’s news on its $25M Series B, including prior auth or step edits, and are codes available?
  Medicare covers CAR-T under NCD 110.24 and maps inpatient episodes to MS-DRG 018, but in-vivo modalities may need interim coding and pricing solutions before product-specific HCPCS are assigned, with payers likely to require prior authorization similar to ex-vivo CAR-Ts (CMS NCD 110.24, CGS MS-DRG 018 guidance, ASTCT coding options).

Publisher / Disclosure

Publisher: LucidQuest Ventures Ltd. Produced: 25 Dec 2025, 16:59 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

Vyriad; VV169; LV-169; multiple myeloma; BCMA; in-vivo CAR-T; lentiviral vector; engineered G protein; Stephen Russell; Novartis; Regeneron; Business Wire; BioWorld; ASH 2025; IND; ClinicalTrials.gov; CMS; NCD 110.24; MS-DRG 018; HCPCS; Q2041; Medicare; prior authorization; Kelonia; KLN-1010; Interius; Kite Pharma; Gilead; Orbital Therapeutics; Bristol Myers Squibb; payer access; vector immunogenicity; insertional mutagenesis; manufacturing scale; outpatient administration; serum stability; transduction efficiency.