GENERATION 2.0
Inspired to build the world’s leading high-science retina pipeline
OUR PIPELINE
Our pipeline is designed to address key limitations of today’s therapies and bring new science to the treatment of retinal diseases.
OUR CANDIDATES
Tarcocimab tedromer
1 Molecule, 1 Target
KSI-501
1 Molecule, 2 Targets
Triplet Medicines
1 Molecule, Many targets
Tarcocimab tedromer1 Molecule, 1 Target
An investigational anti-VEGF biologic designed for class-leading durability
Tarcocimab tedromer is designed to maintain potent and effective drug levels in ocular tissues for longer than existing anti-VEGF therapies.
Built on our proprietary Antibody Biopolymer Conjugate (ABC) Platform, tarcocimab tedromer is purposefully designed with a science for durability and is being studied as a 6-month durability therapy with a strong focus in diabetic eye disease.
Unique potential for long-interval dosing while preserving the flexibility to dose monthly
1.Across five tarcocimab tedromer pivotal studies for diabetic macular edema, diabetic retinopathy, retinal vein occlusion and wet age-related macular degeneration.
2.According to the product label for aflibercept, ranibizumab, faricimab and expectations for high-dose aflibercept (reported clinical data).
Five Phase 3 studies across high-prevalence retinal diseases with a focus in diabetic eye disease
TARCOCIMAB TEDROMER FOR DIABETIC MACULAR EDEMA
Approximately 30% of patients with diabetes have diabetic retinopathy (DR) and are at risk for vision loss, but many of these patients are unaware because they do not have symptoms and do not receive timely and regular vision care. For those diagnosed with DR, physicians typically wait to treat until the patient progresses or develops a sight-threatening complication such as diabetic macular edema due to the onerous burden of frequent intravitreal injections required by existing anti-VEGF agents. This delayed treatment approach does not lead to the best vision outcomes for patients as untreated patients often progress, developing vision-threatening complications that are preventable if treated early.
Our lead investigational medicine, tarcocimab tedromer, is a novel anti-VEGF biologic in a Phase 3 clinical study for non-proliferative diabetic retinopathy (NPDR). It is designed to evaluate tarcocimab’s efficacy as a once every six-month treatment in preventing vision-threatening complications and reversing DR severity for patients with NPDR. Tarcocimab demonstrated extended ocular half-life in pre-clinical studies and is expected to provide an important dosing advantage compared to established anti-VEGF therapies.
Tarcocimab is purposefully built with a science of durability, in our case the science of our Antibody Biopolymer Conjugate (ABC) platform, and both the molecule and pivotal program are designed to demonstrate twice yearly dosing for diabetic eye disease, including DME and NPDR. Tarcocimab could be a potential gamechanger for diabetes patients by providing the opportunity for real prevention of vision loss.
TARCOCIMAB TEDROMER FOR DIABETIC RETINOPATHY
Today’s standard of care for patients with diabetic macular edema (DME) is intravitreal injections that target VEGF. Established anti-VEGF therapies require frequent injections, often monthly to every 3 months for the majority of patients. Many patients are not able to adhere to this burdensome treatment schedule, as demonstrated by the fact that about 30% of patients with DME discontinue treatment in any given year, putting them at high risk for vision loss and blindness. Newly approved anti-VEGF agents demonstrated efficacy with every 4-month dosing in clinical trials for some patients but their durability in the real world remains to be proven.
Our lead investigational medicine, tarcocimab tedromer, is a novel anti-VEGF biologic in two Phase 3 clinical studies for DME and is designed to demonstrate 6-month durability for the majority of patients, while preserving flexibility for monthly dosing for high-need patients, providing patients and physicians a broad spectrum of dosing regimens not offered by other anti-VEGFs. Tarcocimab demonstrated extended ocular half-life in pre-clinical studies and is expected to provide an important dosing advantage compared to established anti-VEGF therapies and to provide patients with long-term control of their DME while reducing the injection burden.
Tarcocimab is purposefully built with a science of durability, in our case the science of our Antibody Biopolymer Conjugate (ABC) platform, and both the molecule and pivotal program are designed to provide long-interval durability by demonstrating twice yearly dosing for diabetic eye disease, including DME and NPDR.
TARCOCIMAB TEDROMER FOR WET AMD
Our lead investigational medicine, tarcocimab tedromer, is a novel anti-VEGF biologic that includes an anti-VEGF antibody stably conjugated to a phosphorylcholine biopolymer, the central tenet of our Antibody Biopolymer Conjugate (ABC) platform.
Tarcocimab tedromer is administered as an intravitreal injection and demonstrated strong efficacy in 59% of wet AMD patients who were treated every 5 months and comparable safety to standard of care anti-VEGF therapy aflibercept dosed every two months in our Phase 2b/3 study in wet AMD patients. It is currently being studied in the Phase 3 DAYLIGHT study as a monthly treatment against aflibercept dosed every two months to provide the flexibility of monthly dosing for patients that need frequent injections. Primary results of the Phase 2b/3 study, evaluating tarcocimab tedromer’s efficacy, durability and safety, are now available here
TARCOCIMAB TEDROMER FOR RETINAL VEIN OCCLUSION
Current standard of care for retinal vein occlusion (RVO) are anti-VEGF therapies that require monthly intravitreal injections to achieve optimal outcomes. However, many patients are unable to adhere to this intensive dosing regimen and real-world outcomes for RVO patients do not meet the promise shown in clinical trials.
Our lead investigational medicine, tarcocimab tedromer, is a novel anti-VEGF biologic that achieved positive primary outcomes in the Phase 3 BEACON study in RVO. This pivotal study showed that tarcocimab tedromer doubled the treatment interval from monthly to every other month while achieving similar vision improvement for RVO patients compared to standard of care dosed monthly. Tarcocimab is the only anti-VEGF therapy that has demonstrated similar vision outcomes in RVO with a doubling of the treatment interval for all patients versus monthly aflibercept. Primary results available here.
Tarcocimab is purposefully built with a science of durability, in our case the science of our Antibody Biopolymer Conjugate (ABC) platform and is expected to provide an important dosing advantage in RVO compared to established anti-VEGF therapies.
Results from our Phase 1b and Phase 3 BEACON studies
Tarcocimab tedromer has consistently shown strong durability data in early and late-stage clinical studies.
BEACON Phase 3 study in RVO:
Tarcocimab Q8W was non-inferior to aflibercept Q4W1
1. The Phase 3 BEACON study is a global, multi-center, randomized study designed to evaluate the durability, efficacy and safety of tarcocimab tedromer Q8W vs. aflibercept Q4W in patients with macular edema due to RVO. NCT04592419 (https://clinicaltrials.gov/show/NCT04592419)
- Tarcocimab Q8W is the first anti-VEGF therapy to demonstrate non-inferiority to monthly aflibercept while doubling the treatment interval from monthly to every-other-month dosing
- Tarcocimab Q8W improved BCVA and OCT CST comparably to aflibercept Q4W from baseline to Week 24 in all RVO patients
- Primary results available here
Phase 1b study in DME, RVO and wet AMD:
Over 2/3 of patients were on a 6-month or longer treatment-free interval at Year 12
2. Phase 1b is a randomized, open label study to evaluate multidose safety, efficacy and durability in wet AMD, DME and RVO. 2.5 & 5 mg doses pooled. Includes only patients that received all (3) loading doses and either a) received a dose before Week 52 or b) did not receive a dose and were followed for at least six months after the last loading dose (Week 32 visit). Interval at Year 1 reflects the treatment interval ongoing at the Week 52 visit (where available) or the last interval before Week 52.
- 69% of patients with DME were on a 6-month or longer treatment-free interval at Year 1 after 3 loading doses. Mean BCVA gain of +7.6 ETDRS letters
- 66% of patients with RVO and wet AMD were on a 6-month or longer treatment-free interval at Year 1 after 3 loading doses
- One-year results available here
Tarcocimab tedromer and the ABC Platform are purposefully designed for increased durability
See how tarcocimab compares to today's anti-VEGF molecules →
HOW TARCOCIMAB COMPARES TO TODAY'S ANTI-VEGF MOLECULES
Learn more about the science of our ABC Platform →
Tarcocimab tedromer aims to maintain therapeutic activity for longer.
KSI-5011 Molecule, 2 Targets
An investigational first-in-class dual inhibitor biologic designed to address both vascular permeability and inflammation
Inflammation has been shown to play a significant role in retinal vascular disease. However, no treatments exist that concurrently address vascular permeability and inflammation.
KSI-501, our second investigational medicine built on our Antibody Biopolymer Conjugate (ABC) platform, is designed to inhibit VEGF and IL-6, a pro-inflammatory cytokine and immune growth factor, combining two powerful mechanisms of action to address retinal vascular disease and the underlying inflammatory cascade.
KSI-501: two powerful mechanisms of action that may enhance efficacy beyond anti-VEGFs
IL-6 levels are significantly elevated in eyes with retinal vascular disease and are implicated in anti-VEGF treatment resistance
Vitreous IL-6 levels in patients with retinal vascular disease vs. control1
DME: diabetic macular edema; PDR: proliferative diabetic retinopathy; BRVO: branch retinal vein occlusion; CRVO: central retinal vein occlusion; RD: retinal detachment.
1. Yoshimura et al. (2009). PLoS ONE 4(12): e8158.
Aqueous humor IL-6 levels significantly correlate with anti-VEGF treatment response in wet AMD2
2. Adapted from Chalam et al. (2014). Journal of Ophthalmology, Article ID 502174. Mean with SEM plotted.
A significant portion of DME patients (30%-66%) have evidence of persistent disease activity despite frequent anti-VEGF treatment
In pre-clinical studies, dual inhibition of VEGF and IL-6 by KSI-501 demonstrated normalization of inner and outer blood retinal barriers compared to anti-VEGF or anti-IL-6 monotherapy
Inner blood-retinal barrier: leakage from vascular endothelium disruption leads to macular edema and hemorrhage
Outer blood-retinal barrier: RPE integrity prevents choroidal vascularization from invading the retina
Orphan development path with concurrent exploration in high-prevalence retinal diseases
The ongoing Phase 1 study is in DME initially with the possibility to expand into uveitic macular edema (UME).
HOW KSI-501 CAN HELP
Today’s standard of care treatments for retinal vascular diseases are designed to target VEGF alone. However, many patients with retinal vascular disease do not respond well to anti-VEGF monotherapies. Our second investigation medicine, KSI-501, is a first-in-class bispecific Antibody Biopolymer Conjugate (ABC) designed to target VEGF and IL-6, thereby addressing the concurrent inflammation and abnormal angiogenesis and vascular leakage observed in the pathogenesis of retinal vascular diseases.
KSI-501 is an anti-VEGF and anti-IL-6 biopolymer conjugate designed to provide dual and potent inhibition of (i) VEGF-mediated angiogenesis and vascular permeability through a soluble decoy receptor inhibiting the binding of VEGF-A and PLGF to their cognate receptors and (ii) IL-6 mediated inflammation through an antibody that binds soluble interleukin-6, inhibiting its binding to both soluble and membrane-bound IL-6 receptors. In cell-based assays KSI-501 inhibits angiogenesis and normalizes inner and outer blood retinal barriers; dual inhibition of VEGF and IL-6 by KSI-501 confers superior normalization of cell morphology and junctional biology compared to either anti-VEGF or anti-IL-6 monotherapy.
We believe KSI-501 has the potential to become a new category of retinal medicines with greater therapeutic efficacy than existing therapies while also benefiting from the promising long-interval durability of Kodiak’s ABC Platform.
The initial pivotal program is likely to be in UME because there is a high unmet need for patients with UME:
Uveitis features chronic intraocular inflammation that can result in UME that is often resistant to anti-VEGF monotherapy
There is no approved targeted therapy for UME
Patients may require treatment with systemic or intravitreal steroids, immunosuppressants and/or biologics, each of which can have serious side effects
Additional indications to be explored include DME and wet AMD. In DME, there is strong preclinical and clinical evidence on the role of IL-6 in driving inflammation and anti-VEGF treatment response. In wet AMD, there is preclinical evidence IL-6 is implicated in the development of exudative choroidal neovascularization and clinical evidence suggesting elevated aqueous IL-6 levels in patients with low or no anti-VEGF treatment response.
Our goal with KSI-501 is to develop a first-in-class biologic by combining two powerful mechanisms of action – anti-immune (new) and anti-permeability (core of therapy today) – for high-prevalence retinal disease and orphan disease UME
Triplet Medicines1 Molecule, Many targets
Multi-mechanism, multi-modality targeted biologic for complex retinal and systemic diseases
Triplet medicines combine the benefits of our Antibody Biopolymer Conjugate (ABC) Platform for long-interval dosing of biologics with a new feature that adds sustained release of 100s of small molecules to target three or more mechanisms of action, enabling treatment of complex, multifactorial diseases.
Designing a new generation of targeted therapy for high-prevalence multifactorial diseases
Our triplet ABC medicines aim to broaden what’s possible with antibody conjugate therapies
Antibody Drug Conjugate (ADC) therapies are revolutionizing the way cancer is treated today by delivering highly potent cancer-killing agents directly to cancer cells via a targeted antibody. With our ABC triplet medicines, we aim to build on this foundation in notable ways:
ADC
- Primarily developed to treat cancer today
- Constrained by its Drug Antibody Ratio (DAR) of up to 8
- Limited to using small molecules that are highly potent and cytotoxic with serious side effects
- Antibody primarily serves as a targeting agent to deliver cytotoxic small molecules to cancer cells
ABC Triplet Medicine
- Designed for ophthalmic and also systemic diseases such as cancer
- Designed to provide DARs of 50, 100 and up to 250 by embedding the biopolymer with small molecules
- Enables the use of mechanistic small molecules rather than cytotoxins
- Biopolymer can also be stably linked to a protein therapeutic (e.g., antibody)
- Same durability benefit enabled by the ABC Platform
- Antibody can be designed to target a cell or a biological pathway
Our goal with our triplet medicines is to deliver greater therapeutic benefit for multifactorial diseases in the eye and systemically by modulating multiple distinct pathological processes in parallel
How tarcocimab compares to today’s anti-VEGF molecules
An investigational anti-VEGF biologic designed for long-interval dosing
Tarcocimab tedromer is designed to maintain potent and effective drug levels in ocular tissues for longer than existing anti-VEGF therapies.
Built on our proprietary Antibody Biopolymer Conjugate (ABC) Platform, tarcocimab tedromer is purposefully designed with a science for durability and is being studied as a 6-month durability therapy with a strong focus in diabetic eye disease.
Unique potential for long-interval dosing while
preserving the flexibility to dose monthly
- Across five tarcocimab tedromer pivotal studies for diabetic macular edema, diabetic retinopathy retinal vein occlusion and wet age-related macular degeneration.
- According to the product label for aflibercept, ranibizumab, faricimab and expectations for high-dose aflibercept (reported clinical data).
Five Phase 3 studies across high-prevalence retinal diseases with a focus in diabetic eye disease
Results from our Phase 1b and Phase 3 BEACON studies
Tarcocimab tedromer has consistently shown strong durability data in early and late-stage clinical studies.
BEACON Phase 3 study in RVO:
Tarcocimab Q8W was non-inferior to aflibercept Q4W1
- Tarcocimab Q8W is the first anti-VEGF therapy to demonstrate non-inferiority to monthly aflibercept while doubling the treatment interval from monthly to every-other-month dosing
- Tarcocimab Q8W improved BCVA and OCT CST comparably to aflibercept Q4W from baseline to Week 24 in all RVO patients
- Primary results available here
- The Phase 3 BEACON study is a global, multi-center, randomized study designed to evaluate the durability, efficacy and safety of tarcocimab tedromer Q8W vs. aflibercept Q4W in patients with macular edema due to RVO. NCT04592419 (https://clinicaltrials.gov/show/NCT04592419)
Phase 1b study in DME, RVO and wet AMD:
Over 2/3 of patients were on a 6-month or longer treatment-free interval at Year 12
- 69% of patients with DME were on a 6-month or longer treatment-free interval at Year 1 after 3 loading doses. Mean BCVA gain of +7.6 ETDRS letters
- 66% of patients with RVO and wet AMD were on a 6-month or longer treatment-free interval at Year 1 after 3 loading doses
- One-year results available here
- Phase 1b is a randomized, open label study to evaluate multidose safety, efficacy and durability in wet AMD, DME and RVO. 2.5 & 5 mg doses pooled. Includes only patients that received all (3) loading doses and either a) received a dose before Week 52 or b) did not receive a dose and were followed for at least six months after the last loading dose (Week 32 visit). Interval at Year 1 reflects the treatment interval ongoing at the Week 52 visit (where available) or the last interval before Week 52.
Tarcocimab tedromer and the ABC Platform are purposefully designed for increased durability
Tarcocimab tedromer aims to maintain therapeutic activity for longer.
An investigational first-in-class dual inhibitor biologic designed to address both vascular permeability and inflammation
Inflammation has been shown to play a significant role in retinal vascular disease. However, no treatments exist that concurrently address vascular permeability and inflammation.
KSI-501, our second investigational medicine built on our Antibody Biopolymer Conjugate (ABC) platform, is designed to inhibit VEGF and IL-6, a pro-inflammatory cytokine and immune growth factor, combining two powerful mechanisms of action to address retinal vascular disease and the underlying inflammatory cascade.
KSI-501: two powerful mechanisms of action that may enhance efficacy beyond anti-VEGFs
IL-6 levels are significantly elevated in eyes with retinal vascular disease and are implicated in anti-VEGF treatment resistance
Vitreous IL-6 levels in patients with retinal vascular disease vs. control1
DME: diabetic macular edema; PDR: prolifera tive diabetic retinopathy; BRVO: branch retinal vein occlusion; CRVO: central retinal vein occlusion; RD: retinal detachment.
1.Yoshimura et al. (2009). PLoS ONE 4(12): e8158.
Aqueous humor IL-6 levels significantly correlate with anti-VEGF treatment response in wet AMD2
A significant portion of DME patients (30%-66%) have evidence of persistent disease activity despite frequent anti-VEGF treatment
In pre-clinical studies, dual inhibition of VEGF and IL-6 by KSI-501 demonstrated normalization of inner and outer blood retinal barriers compared to anti-VEGF or anti-IL-6 monotherapy
Inner blood-retinal barrier: leakage from vascular endothelium disruption leads to macular edema and hemorrhage
Outer blood-retinal barrier: RPE integrity prevents choroidal vascularization from invading the retina
Orphan development path with concurrent exploration in high-prevalence retinal diseases
The ongoing Phase 1 study is in DME initially with the possibility to expand into uveitic macular edema (UME).
The initial pivotal program is likely to be in UME because there is a high unmet need for patients with UME:
Additional indications to be explored include DME and wet AMD. In DME, there is strong preclinical and clinical evidence on the role of IL-6 in driving inflammation and anti-VEGF treatment response. In wet AMD, there is preclinical evidence IL-6 is implicated in the development of exudative choroidal neovascularization and clinical evidence suggesting elevated aqueous IL-6 levels in patients with low or no anti-VEGF treatment response.
Our goal with KSI-501 is to develop a first-in-class biologic by combining two powerful mechanisms of action – anti-immune (new) and anti-permeability (core of therapy today) – for high-prevalence retinal disease and orphan disease UME
Multi-mechanism, multi-modality targeted biologic for complex retinal and systemic diseases
Triplet medicines combine the benefits of our Antibody Biopolymer Conjugate (ABC) Platform for long-interval dosing of biologics with a new feature that adds sustained release of 100s of small molecules to target three or more mechanisms of action, enabling treatment of complex, multifactorial diseases.
Designing a new generation of targeted therapy for high-prevalence multifactorial diseases
Our triplet ABC medicines aim to broaden what’s possible with antibody conjugate therapies
Antibody Drug Conjugate (ADC) therapies are revolutionizing the way cancer is treated today by delivering highly potent cancer-killing agents directly to cancer cells via a targeted antibody. With our ABC triplet medicines, we aim to build on this foundation in notable ways:
ADC
|
ABC Triplet Medicine
|
Our goal with our triplet medicines is to deliver greater therapeutic benefit for multifactorial diseases in the eye and systemically by modulating multiple distinct pathological processes in parallel