July 2019
Volume 60, Issue 9
ARVO Annual Meeting Abstract  |   July 2019
Phase 1 first-in-human study of KSI-301: a novel anti-VEGF antibody biopolymer conjugate with extended durability
Author Affiliations & Notes
  • Sunil S Patel
    Retina Research Institute of Texas, Abilene, Texas, United States
  • Joel Naor
    Kodiak Sciences Inc., Palo Alto, California, United States
  • Almas Qudrat
    Kodiak Sciences Inc., Palo Alto, California, United States
  • Diana V Do
    Ophthalmology, Byers Eye Institute, Stanford University School of Medicine, California, United States
  • Desiree Buetelspacher
    Kodiak Sciences Inc., Palo Alto, California, United States
  • hong liang
    Kodiak Sciences Inc., Palo Alto, California, United States
  • D. Victor Perlroth
    Kodiak Sciences Inc., Palo Alto, California, United States
  • Footnotes
    Commercial Relationships   Sunil Patel, Kodiak Sciences Inc. (C); Joel Naor, Kodiak Sciences Inc. (E); Almas Qudrat, Kodiak Sciences Inc. (E); Diana Do, Kodiak Sciences Inc. (C); Desiree Buetelspacher, Kodiak Sciences Inc. (E); hong liang, Kodiak Sciences Inc. (E); D. Victor Perlroth, Kodiak Sciences Inc. (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3670. doi:
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      Sunil S Patel, Joel Naor, Almas Qudrat, Diana V Do, Desiree Buetelspacher, hong liang, D. Victor Perlroth; Phase 1 first-in-human study of KSI-301: a novel anti-VEGF antibody biopolymer conjugate with extended durability. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3670.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : Real world vision outcomes of anti-VEGF therapy are limited by the high treatment burden of existing agents. KSI-301 is a novel antibody biopolymer conjugate that inhibits VEGF. Its design optimized both size and molar dose to improve intraocular durability. With a molecular weight of 950 kDa achieved by site-specific conjugation of an antibody to an 800 kDa branched phosphorylcholine biopolymer, KSI-301 demonstrates high bioavailability to key ocular tissues (retina and choroid/RPE), has high affinity for VEGF (KD 6.75 pM), and is delivered via standard intravitreal injection. In the rabbit ocular pharmacokinetic model KSI-301 has ocular tissue half-lives of 10+ days in the retina and 12.5+ days in the choroid in comparison to 3-4 days for Lucentis and 4-5 days for Eylea. This first-in-human study sought to evaluate initial safety and tolerability of KSI-301, and to establish a maximum tolerated dose. Bioactivity was evaluated by measuring visual function and retinal anatomy.

Methods : Previously-treated or naïve subjects with DME were eligible. In this open-label, single ascending dose study, study eyes received one intravitreal injection of KSI-301 (1.25 mg, 2.5 mg, or 5 mg) and were then followed for 12 weeks. The primary endpoint was Week 2. Three subjects were enrolled in each cohort; dose escalation was based on review by a DSMC.

Results : Nine subjects were enrolled. The Phase 1 study met its objective of safety and tolerability. At the primary endpoint, no drug-related adverse events, no intraocular inflammation, and no dose-limiting toxicities were observed. All dose levels were well tolerated. After a single dose of KSI-301, rapid-onset, high-magnitude improvements in BCVA with corresponding reductions in macular thickness on OCT were observed at all dose levels. The patients are continuing to be followed through 12 weeks.

Conclusions : A single intravitreal injection of KSI-301 was safe and well tolerated at all dose levels tested. Bioactivity was demonstrated at all dose levels providing a preliminary proof-of-concept for KSI-301 in retinal vascular diseases and for the antibody biopolymer conjugate approach. The results support continued clinical development of KSI-301; a multiple-dose Phase 1b study in patients with wet AMD, DME, or RVO is now underway, and a series of Phase 2 studies in wet AMD and DME is being planned.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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