Carna Biosciences, Inc.

Carna Biosciences, Inc.

Pipeline

Carna has leveraged its expertise in kinase biology to establish an innovative product pipeline focused on cancer and immune disorders. We achieve success by coupling our deep understanding of cell signaling with our extensive drug discovery expertise to generate therapeutics that inhibit kinases and provide new treatment options for patients with high unmet medical needs.

  • COMPOUND
  • TARGET
    • Discovery
    • Preclinical
    • Early Clinical
    • Late Clinical
  • PARTNER
  • REGION
  • AS-0141
  • TARGET: CDC7/ASK
  • Discovery Preclinical Early Clinical Late Clinical
  • PARTNER:
  • REGION:
AS-0141
AS-0141 is a potent, selective, orally bioavailable small molecule inhibitor of CDC7 kinase, originally discovered by Carna. AS-0141 exhibited a potent anti-proliferative activity against various cancer cell lines including solid and blood cancers with minimal effects against normal cells. In several human tumor xenograft models, oral administration of AS-0141 demonstrated strong anti-tumor efficacy. AS-0141 is currently being evaluated in an open-label Phase I study in patients with unresectable advanced, recurrent, or metastatic solid tumors. This study consists of two parts: the dose escalation part that aims to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of AS-0141 and the expansion cohort aimed at ensuring the appropriateness of PR2D and evaluating the preliminary anti-tumor effect.
CDC7
CDC7 (cell division cycle 7) is a serine-threonine kinase that plays a critical role in DNA synthesis and is required for the activation of DNA replication origins throughout the S phase of the cell cycle. Inhibition of CDC7 in cancer cells causes lethal S phase or M phase progression, whereas normal cells survive, most likely through induction of cell cycle arrest at the DNA replication checkpoint. It has been reported in the literature that CDC7 is overexpressed in many cancers including colon cancer, kidney cancer, bladder cancer, breast cancer, cervical cancer and leukemia.
  • Small
    Molecule
  • TARGET: Kinase
  • Discovery Preclinical Early Clinical Late Clinical
  • PARTNER: Gilead Sciences
  • REGION: Worldwide
  • Small
    Molecule
  • TARGET: Kinase
  • Discovery Preclinical Early Clinical Late Clinical
  • PARTNER: Sumitomo Dainippon Pharma
  • REGION: Worldwide
  • AS-0871
  • TARGET: BTK
  • Discovery Preclinical Early Clinical Late Clinical
AS-0871
AS-0871 is an investigational small molecule drug designed to bind non-covalently to Bruton's tyrosine kinase (BTK) with high selectivity, currently in development for inflammatory and immune disorders. In in vitro experiments, AS-0871 strongly inhibited B cell and basophil activation and suppressed production of inflammatory cytokines such as TNF-α, IL-17, MCP-1 and IL-6 in human blood. Oral administration of AS-0871 demonstrated the excellent therapeutic effects in a mouse model of collagen-induced arthritis. In addition, AS-0871 prevented IgE-mediated skin inflammation in mice and rats.
In a First-in-Human Phase I randomized single ascending dose (SAD) study in healthy volunteers (EudraCT 2019-004348-31), AS-0871 was safe and well-tolerated at all dose levels tested from 25 mg to 900 mg. AS-0871 achieved plasma level to demonstrate pharmacodynamic effects with strong inhibition of anti-IgD-induced CD69 expression in naïve B cells and anti-IgE-induced CD63 expression in basophils at doses of 100 mg and above.
A multiple ascending dose study to confirm the safety and tolerability and to determine the effective doses for Phase 2 is scheduled to begin in the second half of 2021.
BTK inhibitors in inflammatory and immune disorders
BTK is a Tec family tyrosine kinase expressed in B cells and myeloid cell populations including monocytes, macrophages, neutrophils, basophils and mast cells. BTK has a crucial role in B cell antigen receptor (BCR) signaling during B cell development and activation. In autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus, aberrant BCR signaling is considered to promote diseases through production of autoantibodies. In addition to BCR signaling, BTK mediates downstream signaling of the Fcγ receptors in myeloid cells to produce inflammatory cytokines such as IL-6 and TNF-α, which would aggravate RA symptoms. In allergic diseases, BTK is a critical enzyme for Fcɛ receptor (FcɛR) signaling in mast cells and basophils to regulate release of chemical mediators such as histamine and leukotrienes. Therefore, BTK is being paid attention as an attractive therapeutic target for the treatment of autoimmune diseases and allergic diseases.
  • AS-1763
  • TARGET: BTK
  • Discovery Preclinical Early Clinical Late Clinical
AS-1763
AS-1763 is a highly selective, orally bioavailable, non-covalent inhibitor of both the wild type and C481S mutant Bruton’s tyrosine kinases (BTK) for the treatment of chronic lymphocytic leukemia (CLL) and other B cell malignancies. First generation covalent BTK inhibitors including ibrutinib are key therapeutic options for patients with B cell malignancies. However, patients are reported to develop resistance during the treatment due to substitution of cysteine residue at 481 position with serine (C481S mutation) in BTK, which prevents the covalent binding of the first generation irreversible BTK inhibitors. In in vitro experiments, AS-1763 significantly abrogates cell proliferation in both wild type and C481S mutant BTK lymphoma cells, strongly suggesting AS-1763 will be a new therapeutic option for treating patients with B cell malignancies both having wild type and C481S mutation in BTK.
A Phase I clinical trial of oral AS-1763 is currently underway in the Netherlands (EudraCT 2020-005599-37). This Phase I study is a randomized, double-blind, placebo controlled, single ascending dose (“SAD”) study in healthy male and female adult subjects, and will assess the safety and tolerability of AS-1763 as primary outcome measures and pharmacokinetics/pharmacodynamics as secondary outcome measures.
BTK inhibitors in CLL and B cell malignancies
BTK plays a crucial role in B cell antigen receptor (BCR) signaling which is essential for B cell development, and BTK has been recognized as a validated therapeutic target for B cell malignancies including CLL. First generation covalent BTK inhibitors have been appreciated as a promising targeted therapy for patients with B cell malignancies. However, the emergence of clinical resistance to these covalent BTK inhibitors is becoming serious concerns. BTK C481S mutation predominantly confers this drug resistance by preventing covalent binding of the first generation BTK inhibitors. Therefore, there is a high unmet medical need for new therapeutic approaches to overcome the BTK C481S-mediated resistance. The next generation non-covalent BTK inhibitor is expected to be a promising option to treat patients with BTK C481S mutation.
  • AS-1763
    (BN102)
  • TARGET: BTK
  • Discovery Preclinical Early Clinical Late Clinical
  • PARTNER: BioNova Pharmaceuticals
  • REGION: China
  • Small
    Molecule
  • TARGET: ALK5
  • Discovery Preclinical Early Clinical Late Clinical
  • Small
    Molecule
  • TARGET: malaria
  • Discovery Preclinical Early Clinical Late Clinical
  • Small
    Molecule
  • TARGET: CDK1
  • Discovery Preclinical Early Clinical Late Clinical
  • Small
    Molecule
  • TARGET: STING
  • Discovery Preclinical Early Clinical Late Clinical