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Updates abound in this year’s AMD pipeline poster
Download the Pipeline PDFsThis content originally ran as a poster in the May/June issue. Check out the print publication to view the full size poster, or use the links below to download the PDFs.
Dry AMD Pipeline PDFWet AMD Pipeline PDFWatch as Peter K. Kaiser, MD, explains the poster and follow along with the graphics below.
Every year I update this poster —now in its fifth iteration (for those keeping score at home)—to give my fellow retina specialists a quick snapshot of where we stand in drug development. It’s made for those of us juggling packed clinics and barely enough time to breathe. What should you know about? What should you keep an eye on? And what major changes to the treatment landscape and developmental pipeline are worth highlighting?
In terms of wet age-related macular degeneration (AMD), I decided to remind my retina specialist colleagues about the redesigned Port Delivery System with Ranibizumab (Genentech/Roche). This technology is back in the treatment armamentarium for retina specialists (Spoiler alert: the new septum-overmold bond is sturdier and hopefully may prevent septum dislodgement). We also introduce readers to the wingless integration signaling pathway (Wnt, pronounced “wint”), which researchers have begun targeting. Although we are years away from a potential treatment that leverages this pathway, we nevertheless should keep it on our radar.
The ever-expanding dry AMD section of this year’s poster continues a familiar trend—steady growth in the pipeline. While we’ve seen a few failures, the number of new treatments, spanning a wide range of mechanisms, continues to climb.
Rethinking how to organize the summary of dry AMD treatments posed some unique challenges. For example, the longest list of pipeline treatments falls under the “Suppress Inflammation” section, and to square the realities of print layout and page real estate, we placed it most prominently on the left side of the poster. This does not mean, however, that these options are furthest upstream in the dry AMD treatment flowchart, nor are they more legitimate than options that appear elsewhere on the poster.
I’d like to call your attention to the box titled, “New Evidence on the Efficacy of AREDS Supplements in AMD,” which explores a recent study showing that certain combinations of oral micronutrient supplementation could play an important role in mitigating the risk of vision loss in patients with GA.1 AREDS vitamins remain one of our oldest options, but age has not made them any less useful. If you’re looking for a surprising update, don’t skip this callout box.
As always, we are eager to hear your suggestions, comments, and criticisms of this annual poster. If you need to reach the team that assembles this project so that we can consider your input next year, email me, Peter K. Kaiser, MD, at pkkaiser@gmail.com or Cara Deming, Executive Director of Special Projects at Bryn Mawr Communications, at cdeming@bmctoday.com.
1. Keenan TDL, Agrón E, Keane PA, et al; Age-Related Eye Disease Study Research Group; Age-Related Eye Disease Study 2 Research Group. Oral antioxidant and lutein/zeaxanthin supplements slow geographic atrophy progression to the fovea in age-related macular degeneration. Ophthalmology. 2025;132(1):14-29.
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Click the below to see how certain therapies play a role in treating dry AMD.
MOBILE USERS:
We recommend that you access this portion of the Pipeline on a desktop computer.
While a larger screen will make it easier to navigate and visualize the Suppress Inflammation diagram below, the mobile experience contains the same content.
Send yourself an email reminder to access this page from a computer »Hover the numbers in the diagram or in the list below to see where each therapy suppresses inflammation along the pathway.
See the diagram below showing where each therapy suppresses inflammation along the pathway.
1
OMS721 (Omeros)
MASP-2 Inhibition
2
ANX007 (Annexon)
C1q Inhibition
3
Iptacopan (Novartis)
Complement Factor B Inhibition
4
Pegcetacoplan (Apellis) FDA Approved
C3 Inhibition
5
CB-2782-PEG (Catalyst Biosciences)
C3 Protease
6
AMY106 (Amyndas Pharmaceuticals)
C3 Inhibition
7
SLN501 (Silence Therapeutics/ Mallinckrodt Pharmaceuticals)
siRNA C5 mRNA Inhibition
8
Efdamrofusp alfa (Innovent Biologics)
sCR1/VEGF Inhibition
9
CR1/CR2 Gene Therapy
10
CR1 Gene Therapy
11
NM5072 (NovelMed)
Properdin Inhibition
12
Danicopan (Alexion Pharmaceuticals/AstraZeneca)
Complement Factor D Inhibition
13
BCX9930 (BioCryst Pharmaceuticals)
Complement Factor D Inhibition
14
KNP-301 (Kanaph Therapeutics)
C3b/VEGF Inhibition
15
AGN-151151 (AbbVie)
C5 Inhibition
16
cemdisiran (Alnylam Pharmaceuticals)
siRNA C5 mRNA Inhibition
17
Avacincaptad pegol (Astellas) FDA Approved
C5 Inhibition
18
ALXN1720 (Alexion)
C5 Inhibition
19
pozelimab/cemdisiran (Regeneron)
c5 Inhibition
20
PASylated Nomacopan (Akari Therapeutics)
C5/LTB4 Inhibition
21
KNP-302 (Kanaph Therapeutics)
C3b and CD59 Inhibition
22
sCD59 Gene Therapy
23
Complement Factor H Gene Therapy
24
Complement Factor H Gene Therapy
25
Short-Form Complement Factor H Gene Therapy
26
Complement Factor H Gene Therapy
27
CB-4332 (Catalyst Biosciences)
Recombinant Complement Factor I
28
AVD-104 (Aviceda Therapeutics)
Complement Factor H Activation
TMi-018 (Translatum Medicus)
Blocks M1 Transcriptome Expression
K8 (Inflammasome Therapeutics)
doxycycline (Galderma Labs)
View More
New research suggests that oral micronutrient supplementation could play an important role in mitigating the risk of vision loss in patients with GA.1
It remains to be seen how retina specialists will apply these data, but they nevertheless suggest that they have another arrow in their quiver.
RORA Anti-imflammatory Protein Gene Therapy
Selective σ-2 Inhibition
Connexin43 Inhibition
Photobiomodulation
FAS Inhibition
DNA Plasmid Expressing Transferrin
siRNA TTR mRNA Inhibition
HMG-CoA Reductase Inhibition
ELOVL2 gene therapy
Ferroptosis Inhibition
Deuterium-Stabilized DHA
Gene Therapy to Reduce Oxidative Stress
Continue to scroll to see which pathway and receptors are targeted with each therapy.
RGX-314 (REGENXBIO, AbbVie) AL-001 (Beijing Along Biopharmaceutical Co) HG202 (HuidaGene Therapeutics Co) ixoberogene soroparvovec (Adverum Biotechnologies) NG101 (Neuracle Genetics) LX102 (InnoStellar Biotherapeutics) E301 (Samsung) FT-003 (Frontera) ABI-110 (Avirmax Biopharma) 4D-150 (4D Molecular Therapeutics) EXG-102-031 (Exogenesis Bio) KH631 (Kanghong Biotech) HG202 (HuidaGene Therapeutics) BD311 (Shanghai BDgene Therapeutics Co) pegaptanib (Bausch + Lomb) FDA approved Port Delivery System (Genentech/Roche) FDA approved ranibizumab (Genentech/Roche) FDA approved ranibizumab-nuna (Samsung/Biogen) FDA approved ranibizumab-eqrn (Sandoz) FDA approved ranibizumab-Ximluci (Xbrane Biopharma) EMA approved ranibizumab-RanizuRel (Reliance Life Sciences) India FDA approved Ranibizumab-razumab (Intas Pharmaceuticals) India FDA approved LUBT010 (Lupin Ltd/Amman) ranibizumab-Ranivisio (Teva) EMA Approved SCT520FF (SinoCellTech) SJP-0133 (Senju Pharma) BCD100 (BIOCND/Qilu) CKD-701 (Chong Jun Dang) Bevacizumab (Genentech/Roche) Off-label Bevacizumab-vikg (Outlook Therapeutics) EMA approved / Ophthalmic Formulation TAB014 (Zhaoke Ophthalmology) CT-P16 (Celltrion) alymsys (Amneal Pharmaceuticals/mAbxience) AK-3008 (Anhui Anke Biotechnology) MIL-60 (Beijing Mabworks Biotech) brolucizumab (Novartis) FDA approved abicipar pegol (Molecular Partners) KNP-301 (Kanaph Therapeutics) tarcocimab tedromer (Kodiak Sciences) VLTR-559 (Valitor) high-dose aflibercept (Regeneron) FDA approved aflibercept (Regeneron) FDA approved aflibercept-ayyh (Amgen) FDA Approved aflibercept-jbvf (Biocon) FDA Approved aflibercept-yszy (Samsung/Biogen) FDA Approved ALT-L9 (Altos Biologics) MYL-1701 (Mylan/Momenta) SB15 (Samsung) RBS-001 (Rophibio) SCD411 (Sam Chun Dang Pharmaceutical Co./Fresenius Kabi) SOK583A1 (Sondoz/Novartis) OT-702 (Ocumension Therapeutics/Shandong Boan) FY203 (Formycon/Coherus) CT-P42 (Celltrion) AVT-06 (Alvotech) conbercept (Kanghong Biotech) CDE Approved IBI302 (Innovent Biologics) IBI333 (Innovent Biologics) ★ AG-73305 (Allgenesis Biotherapeutics) ★ gersizangitide (AsclepiX Therapeutics) faricimab (Genentech/Roche) FDA Approved BI 836880 (Boehringer Ingelheim) ASKG-712 (AffaMed, AskGene Pharma) ABP-201 (AbPro) IBI324 (Innovent Biologics) zifibancimig (Roche) RO-104 (RevOpsis) EB-105 (Eluminex Biosciences)Caveolin Modulator
SRPK1 Inhibitor
Inhibition of Insulin Receptor Substrate 1 (IRS-1)
Melanocortin Receptor Agonist
Bcl-xL inhibitor
Squalamine analog
TGF-Beta2 Antisense Oligonucleotide
Indoleamine 2,3-dioxygenase (IDO) Inhibitor
Block cAMP/Cortactin Pathway
cp-asiRNA-CTGF/CCN2 Inhibitor
FGF2 Inhibitor
FGF2/VEGF Inhibitor
CG-P5 Peptide
CXC Chemokine Receptor 3 Agonist
Anti-VEGF/IL6 Antibody Polymer Conjugate (ABC)
An Intro:
Phosphorylation that occurs after the activation of the wingless integration1 (WNT, sometimes pronounced wint) signaling pathway could be key to the development of AMD.1 Dysregulated WNT signaling may be linked to increased A2E levels in patients with AMD,1 and could contribute to neovascularization.2 Further, the WNT/beta-catenin pathway triggers the aerobic glycolysis cascade, and upregulation of WNT/beta-catenin results in increased concentration of cytosolic lactate, which has been linked to increased expression of VEGF.3
In 2022, a voluntary recall of the PDS occurred following reports of septum dislodgement in real-world patients. Genentech redesigned the PDS and included two important engineering adjustments,1 which have resulted in significantly reduced rates of septum dislodgement:
1. Chang MA. Technical Updates to Port Delivery System With Ranibizumab (PDS) for the Treatment of Neovascular Age-related Macular Degeneration (nAMD), Diabetic Macular Edema (DME), and Diabetic Retinopathy (DR). Paper presented at: 25th Euretina Congress, September 19-22, 2024; Barcelona, Spain.
Image reprinted with permission from Genentech/Roche.
This content originally ran as a poster in the May/June issue. Check out the print publication to view the full size poster, or download the PDFs.
If you wish to include a candidate for wet AMD, dry AMD, or GA therapy in next year's poster, email Peter K. Kaiser, MD, at pkkaiser@gmail.com and Cara Deming, Executive Director of Special Projects, at Bryn Mawr Communications, at cdeming@bmctoday.com.
View previous pipelines to see how it has evolved over the years.
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VGX-0111
