CC, eerste stuk over ARO-AAT
Thanks Vince. Good afternoon everyone and thank you for joining us today. As we have discussed in the past, our driving focus has always been to bring our technology to patients who can benefit from it. This means treating all types of diseases, both common and rare, and getting to any part of the body. Put simply, it means going to where disease is, from a population standpoint and a physiological and anatomical standpoint. As such, we are constantly working to expand the reach of our products to address various populations by scaling our production capabilities, improving administration convenience, and optimizing dosing schedule. We are also constantly striving to expand our proprietary TRiMTM platform to reach new cell types and address new disease areas without adequate treatment options.
By the third quarter of this year, we expect to have clinical candidates targeting four distinct cell types, addressing high prevalence indications such as chronic HBV and cardiovascular disease, to rarer conditions such as cystic fibrosis and AAT liver disease. It was not that long ago that many thought RNAi may only be relevant to conditions with liver-expressed proteins, and even then only for rare diseases. We at Arrowhead have always been committed to reaching different diseases throughout the body and have devoted considerable resources and many years of innovation and effort to strive to make that a reality. We believe that we are now on the cusp of potentially gaining clinical validation and showing the world that RNAi can reach and silence gene targets in the lung, tumor, and skeletal muscle.
We expect a data-rich next couple months, including: ARO-HSD data in NASH patients and those at risk of having NASH, ARO-AAT data in patients with AAT liver disease, ARO-ENAC data in healthy volunteers and a small number of CF patients, ARO-HIF2 data in patients with renal cell carcinoma and ARO-DUX4 data in animal models for FSHD. Three of these expected data readouts relate to three cell types that, to our knowledge, have not been successfully addressed by RNAi in humans. It is not big pharma with tens of thousands of employees and hundreds of billions in market value that may be on the cusp of a breakthrough in one of these areas; it is Arrowhead with less than 300 employees and a market value of approximately $7 billion that may be nearing a breakthrough in all three.
Think about how that positions us for potential value creation over the near, mid, and long-term, and what it says about our ability to innovate and our potential to lead in this field. Our liver directed pipeline already has six candidates in clinical studies, with additional undisclosed programs in preclinical development. In addition, as you’ve seen over the last couple years, once we achieve clinical validation, each successive candidate in the same cell type builds on learnings from each program that went before it. We believe this provides a higher probability of success and lower risk profile than other modalities.
We expect our pipeline to potentially double in size over the next few years. We also hope to access a new cell type every 18 months to 24 months, so we believe our potential for growth will continue to expand dramatically. It’s this leverage that gives us confidence about the future of our company, our rapidly expanding pipeline, and the patients we hope to serve. We believe this represents the future for Arrowhead and for the RNAi field broadly. We’re also making substantial progress on our current pipeline programs with the potential for key value drivers in the near-term.
Let’s talk about a few of these. First, we announced some of the 12-month biopsy results from the 2002 open label study of ARO-AAT last week. We intend to present a fuller dataset at an upcoming medical meeting, pending abstract acceptance, but I want to provide some context. These results were incredibly exciting to us, our partners at Takeda, the investigators in the study, and to the patient community. To review, the results demonstrated that ARO-AAT treatment led to a consistent and substantial reduction in intra-hepatic mutant Z-AAT protein, both monomer and polymer; a consistent decrease in histological globule burden; improvements in fibrosis; and improvements in other relevant biomarkers of liver health.
Specifically, after 48 weeks of treatment with ARO-AAT in cohort 2, the following results were observed: Four of the five patients achieved a one or greater stage improvement in Metavir fibrosis stage, with no worsening of fibrosis in the fifth patient. All five patients demonstrated reductions in histological globule assessment scores; and, total intra-hepatic Z-AAT decreased by 77% to 97%. After only 24 weeks of treatment, the following results were observed: Two of the four patients achieved a one or greater stage improvement in Metavir fibrosis stage, with no worsening of fibrosis in the other two patients. The two patients who improved fibrosis stages during treatment had cirrhosis at baseline. All four patients demonstrated reductions in histological globule assessment scores; and, total intra-hepatic Z-AAT decreased by 72% to 95%.