One liner: Overview of Ikaria Therapeutics, a pre-clinical project to develop a first-in-class therapy for knee osteoarthritis.
This proposal is based on the supporting documents provided by Ikaria, as well as questions and answers to their team, and senior reviews.
If this goes on-chain, the VITA token holders will ratify the WG’s assessment via a decentralized vote
Scientific & business evaluation : Sebastian Brunemeier, Tuan Dinh, Tim Peterson, anonymous senior reviewer
Shepherd : Tim Peterson
Other squad members : Paolo Binetti, Laurence Ion
Ikaria has a joint rejuvenation therapy nearing clinical development based on controlled-release of fenofibrate via injection into the knee. Fenofibrate, a lipid-lowering agent, approved by the FDA for treating dyslipidemia, has been shown to work on age-related diseases. Initial in-vitro and in-vivo studies are promising. The principal investigator (PI) is a world expert on joint ageing and has a strong team, ready to spin off a biotech company and advance the therapy into the clinic.
This proposal is based on the supporting documents provided by Ikaria, questions and answers to their team, and senior reviews.
Osteoarthritis (OA) is a serious, chronic degenerative joint disease that causes pain, structural changes in the joint tissues, and in the long-term, disability in the people affected. It occurs when the cartilage that cushions the ends of bones in your joints gradually deteriorates.
OA incidence increases with age and affects twice as many women as men (see figure below). This disease is potentially related to two hallmarks of ageing: cellular senescence and loss of proteostasis.
Currently, no disease-modifying therapies exist for OA, with treatments (e.g., NSAIDS) targeting symptoms only. Surgery is the last resort therapy but associated with a lot of pain and complications.
With 240 million people affected by OA worldwide and no disease-altering therapeutics currently available, there is a large market opportunity. There is a strong public health need to reduce reliance on pain medications/opioids for knee OA.
The knee is the most affected joint, therefore it has been selected as the primary target of this project.
An effective therapy would represent a first-in-class drug that could be expanded to other joints and to cover different health areas, mainly those related to age-related diseases.
The applicants propose a new formulation of Fenofibrate (FN) in microspheres as an intra-articular injection (i.e., IA-FN).
Fenofibrate is an approved drug (sold under the brand names Tricor, Fenobrat, etc.) for mainly dyslipidemias, operating as a PPARα agonist, in particular in chondrocytes, the cells responsible for cartilage formation.
The applicants propose a new formulation of FN in microspheres as an IA-FN, a disruptive innovation that provides an extended-release from microspheres for 3 months. The procedure involves local injection that avoids systemic side effects.
This approach is supported by the results of preliminary studies carried out by the team:
- Clinical efficacy of oral FN (O-FN) in a retrospective knee OA cohort of 4796
- Preclinical efficacy of both O-FN and IA-FN in surgically-induced OA in-vivo in mice
In addition, there is an ongoing Phase 2, Randomised, Double-blind, Placebo-controlled Study to evaluate the efficacy and safety of oral FN on quality of life measurements in 216 patients with knee OA.
Since FN is an approved drug with a safe profile, and microspheres are an approved technology for drug delivery, there is a relatively short regulatory path for the IA-FN formulation.
IP is specifically on the intra-articular injection of the novel formulation of FN, IA-FN.
Project leader, Beatriz Carames: Currently Cartilage Biology Unit Group Leader at the Institute of Biomedical Research of A Coruña (INIBIC). Relevant expertise in mechanisms related to OA. BEATRIZ CARAMÉS | SEFAGIA.
Beatriz is supported by clinical and pharmacological expertise within the team:
- Francisco J. Blanco MD, PhD is a Professor of the Medicine Department at the University of A Coruña UDC, a Rheumatologist at the University Hospital of A Coruña (Spain), and a Scientific Director of INIBIC
- Eduardo Domínguez PharmD, PhD is a Senior Researcher at Genomic Medicine group at University of Santiago de Compostela (USC)
- Patricia Díaz PharmD, PhD is an Assistant Professor at Department of Pharmaceutical Technology at USC
- Uxía Nogueira PharmD, PhD. Uxía is a Research Associate in the Cartilage Biology Unit at INIBIC.
Most of the team was previously affiliated with Scripps Research.
This project has already been funded with 1.5 M€ in 2021 by the Spanish Government and the Foundation for Research in Rheumatology, enabling discovery, as well as preliminary validation.
Further funding would support regulatory approval application of IA-FN for OA as a new indication, as well as a Phase I safety trial in individuals with knee OA. The workplan, milestones, and budget breakdown provided by the team are clear and reasonable.
The budget is below.
|Staff Cost||138,000€||Project Manager junior (PhD, MBA): 32.000€ / year (2 years); Scientific operations (PhD): 37.000€ / year (2 years)|
|Services||312.000€||Asphallion: Regulatory roadmap for the development of a new formulation of FN (IA-FN). Budget: 50.000€; Preclinical regulatory for IA-FN trial: CRO for IA-FN formulation (GMP preparation). Budget: 100.000€; Manufacturing of microspheres formulation. Budget: 75.000€; SCReN: Complete management and monitoring of the IA-FN trial will be subcontracted to SCReN to serve as “CRO” for the trial. Budget: 90.000€ (SCReN is the CRO subcontracted for the ongoing FN trial).|
|Ikaria is open to VitaDAO terms, including IP-NFT, royalties, equity blend of deal structure.|
Project Summary: Written Summary.pdf - Google Drive
- “Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy”, U. Nogueira-Recalde, I. Lorenzo-Gómez, F. J. Blanco, M. I. Loza, D. Grassi, V. Shirinsky, I. Shirinsky, M. Lotz, P. D. Robbins, E. Domínguez, B. Caramés, EBioMedicine, 2019
- “Role of the Inflammation-Autophagy-Senescence Integrative Network in Osteoarthritis”, C. Vinatier, E. Domínguez, J. Guicheux, B. Caramés, Frontiers in Physiology, 2018
- “Autophagy and cartilage homeostasis mechanisms in joint health, aging and OA”, M. K. Lotz and B. Caramés, Nat. Rev. Rheumatol, 2011
The authors in bold are Ikaria team members.
- OA represents a significant market with a clear medical need.
- Fenofibrate (FN) is a safe drug that has been shown to work for several age-related conditions, so the chance that it also works for OA is high.
- The team has produced strong supportive evidence of efficacy of the proposed solution OA, both in mice and humans.
- Sound scientific team.
- FN is not a new therapy and is-off patent. The use of microspheres to deliver drugs is not new. So the IP strategy could have some risks.
- Being based in Spain makes fundraising for further clinical trials harder.
- Long study durations in arthritis.
The 4 senior reviewers have expressed a vote in agreement to fund this proposal. Here is the digest:
To quantify the level of conviction, they have provided a score on a scale of 1-5 (with 5 being the highest).
The average score was 4.0/5
Brief qualitative review summaries:
1) “Strong supportive evidence of FN’s potential in OA therapy, both in mice and humans”
2) “Address a clear unmet need. OA is a classic age-driven disease”
3) “Well-established, focused team with a formulation for osteoarthritis (OA). Safe bet”
4) “Clear budget, conscientious team”, “Strong patent position on fenofibrate joint injection”
Here we’ll vote if the Longevity-Dealflow WG’s assessment should go on-chain.
If it succeeds here, the VITA token holders will ratify the WG’s assessment (positive or negative) via a decentralized vote.
- Agree with revisions (please comment)