What changed, and when

Caldera Therapeutics launches with total capital of $112.5 million on 14 Jan 2026, and has dosed first subjects in a Phase 1 healthy-volunteer study of CLD-423, a first-in-class IL-23p19 x TL1A bispecific for inflammatory bowel disease. (Business Wire press release) Independent coverage confirms series financing, clinical start, and that CLD-423 was in-licensed from Qyuns Therapeutics in China. (Fierce Biotech)

An Australian registry entry for CLD-423 details a first-in-human randomized, double-blind, placebo-controlled SAD/MAD design in healthy participants, registered 19 Dec 2025. (ANZCTR record ACTRN12625001454460) Qyuns disclosed HREC approval and a milestone payment from Caldera on 8 Dec 2025, and global rights economics. (Qyuns HKEX voluntary announcement, 9 Dec 2025)

60-second thesis frame

IBD has validated each target independently, with IL-23p19 inhibitors already approved in UC and Crohn’s, and TL1A antibodies showing Phase 2 efficacy, so a well-engineered bispecific that co-blocks IL-23 and TL1A could raise remission depth or durability if safety, PK, and immunogenicity cooperate. (ECCO-JCC review of IL-23p19 use in IBD, 2025, JNJ TREMFYA UC label expansion news, NEJM/PubMed, TL1A mAb tulisokibart Phase 2 UC, MSD program update, tulisokibart)

Caldera now has capital, a clear FIH plan, and a licensor with disclosed economics, but it enters a crowded race that includes pure TL1A antibodies in Phase 3 and other IL-23p19 agents already commercial, so proof that a dual-pathway approach beats best-in-class single agents is the key value unlock. (Business Wire press release, Fierce Biotech, Reuters on TL1A competitor results)

The seven diligence questions

Clinical

• Does CLD-423’s SAD/MAD PK support convenient SC maintenance dosing and adequate TL1A and IL-23 pathway coverage without excessive immunogenicity, per the ANZCTR schema and planned sampling? (ANZCTR record)
• Are safety signals in healthy volunteers clean compared with historical IL-23 and TL1A monotherapies, especially hypersensitivity, infections, and laboratory shifts that could foreshadow combination-pathway risks? (NEJM/PubMed, tulisokibart, ECCO-JCC IL-23p19 review)

Payer or Access

• If efficacy is superior, will payers recognize a step-through exemption versus genericized anti-TNF and established IL-23 regimens, or mandate failure on mono-pathway agents first given cost? (Context: IL-23p19 class already reimbursed in UC and Crohn’s.) (JNJ TREMFYA UC label expansion news)
• Could TL1A class head-to-head or network meta-analyses shift payer preference before CLD-423 hits Phase 2, raising evidence hurdles for a bispecific? (Reuters on TL1A competitor results)

Ops or Adoption

• Can Caldera secure Phase 2 global site start-up and drug supply while running assays for dual-pathway PD biomarkers to de-risk dose selection timelines outlined in the registry? (ANZCTR record)

Competitive

• What is the differentiation plan against late-stage TL1A monotherapies and approved IL-23p19 drugs, and are there other IL-23 x TL1A bispecifics on similar timelines that could crowd first-in-class claims? (Fierce Biotech, ScienceDirect review on TL1A and bispecifics in IBD)

Team or Cap table

• Are governance and economics with Qyuns aligned for fast global development, and do milestone and royalty terms leave room for future crossover or partnering without overhang? (Qyuns HKEX voluntary announcement)

Red flags

• Failure to show clean safety or acceptable immunogenicity in HV SAD/MAD would stall the dual-pathway thesis before patient PoC. (ANZCTR record)
• Inability to outperform best-available single-pathway benchmarks in UC or Crohn’s would blunt payer and physician enthusiasm. (JNJ TREMFYA UC label expansion news, Reuters on TL1A competitor results)
• Class competition advances quickly, for example TL1A antibodies moving into Phase 3 in 2025, compressing the window to demonstrate superiority. (MSD program update, tulisokibart, Fierce Biotech)

Next catalyst

Initial Phase 1 SAD cohort completion and first safety or PK update from the ongoing HV study, followed by MAD initiation per the registered design in Australia. (ANZCTR record, Business Wire press release)

FAQ

• What exactly changed by Caldera’s launch news on 14 Jan 2026, and why does it matter for IBD?
  Caldera disclosed total capital of $112.5 million and first dosing in a Phase 1 HV study of CLD-423, a bispecific targeting IL-23p19 and TL1A, marking clinical entry for a dual-pathway IBD strategy. (Business Wire press release, Fierce Biotech)
• What is the regulatory path after first subject dosed in Caldera’s Phase I and where is the trial registered?
  The first-in-human SAD/MAD trial is registered in Australia and includes IV and SC dosing, standard Phase 1 safety and PK endpoints, and extended follow-up. Next formal steps are completion of SAD cohorts, MAD start, and patient PoC protocol submission. (ANZCTR record)
• Which prior data make IL-23p19 and TL1A credible targets for an IBD bispecific?
  IL-23p19 inhibitors are approved in UC and Crohn’s, while TL1A antibodies have shown randomized Phase 2 efficacy in UC and are advancing to Phase 3. These precedents support the biological rationale for dual blockade. (ECCO-JCC IL-23p19 review, NEJM/PubMed, tulisokibart, MSD program update)
• How was Caldera’s CLD-423 sourced, and what are the disclosed economics with the licensor?
  CLD-423 was in-licensed from Qyuns Therapeutics, which reported HREC approval, a US$5 million milestone receipt, and potential future milestones up to US$540 million plus royalties under a global license signed in April 2025. (Qyuns HKEX voluntary announcement, Fierce Biotech)
• How does the competitive landscape affect CLD-423’s bar for success after Caldera’s 14 Jan 2026 announcement?
  With IL-23p19 drugs on market and TL1A antibodies delivering mid-stage wins and heading to Phase 3, CLD-423 must show either superior efficacy or meaningfully better durability, convenience, or safety to win adoption. (JNJ TREMFYA UC label expansion news, Reuters on TL1A competitor results)

Publisher / Disclosure

Publisher: LucidQuest Ventures Ltd. Produced: 15 Jan 2026, 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. © 2026 LucidQuest Ventures Ltd.

Entities / Keywords

Caldera Therapeutics; CLD-423; Qyuns Therapeutics; QX030N; IL-23p19; TL1A; DR3; ulcerative colitis; Crohn’s disease; risankizumab; mirikizumab; guselkumab; tulisokibart; duvakitug; Prometheus Biosciences; Merck MSD; Sanofi; Teva; AbbVie; FutureGen Biopharmaceutical; J&J; FDA; EMA; MHRA; ANZCTR ACTRN12625001454460; HREC; Atlas Venture; LAV; venBio; Omega Funds; Wellington Management; Janus Henderson Investors; healthy volunteers; SAD; MAD; pharmacokinetics; immunogenicity; Australia; HKEX.