Propelling Therapeutics Forward: De-Risking Successes
In line with the Foundation's mission to accelerate Parkinson's disease research, we aim to de-risk the field, making it as attractive as possible for all researchers, particularly industry groups that will play a significant part in commercializing therapies. For the vast majority of the research projects we fund, we do not take a stake in intellectual property or revenue.
The Foundation's team actively manages our portfolio of over 400 grants, using our expertise to share insights, provide assistance and connect awardees with relevant experts when appropriate. In addition to providing supplemental funding, we seek to actively connect these awardees with industry groups to foster collaborations.
Thanks to the Foundation's funding and support, there are several de-risking successes. Key collaborations include:
- AFFiRiS (Austria-based biotech) is focused on developing vaccines for treatment of various diseases
- Following work on a vaccine for Alzheimer's disease, AFFiRiS initiated work on Parkinson's disease with the AFFITOPE® PD01 vaccine, achieving preclincal proof of concept in March 2010
- PD01 targets alpha-synuclein, triggering an immune response, allowing the patient's immune system to reduce this protein
- MJFF provided AFFiRiS funding in 2010 to complete preclinical development of the PD01; work then advanced to a phase I clinical trial
- A second grant was awarded to AFFiRiS in 2011 for a first-in-humans clinical trial to assess safety and tolerability (study currently on-going)
- Following MJFF's support and financial commitment of approximately $2M, AFFiRiS received investments from two venture capital firms, Santo VC and MIG Funds, for a combined investment of €25M, with the option to invest an additional €30M combined.
- In 2014, AFFiRiS announced a €6M grant from the European Union to continue developing vaccines against PD and multiple system atrophy.
- Mutations in the GBA gene are associated with Parkinson's disease and cause a loss of GCase enzyme activity. Such loss could lead to build-up of the protein alpha-synuclein, which leads to cell death in PD.
- Amicus Therapeutics is developing compounds to increase GCase enzyme activity and prevent alpha-synuclein aggregation.
- MJFF funded exploration of one compound, AT2101, in 2006.
- While AT2101 proved effective in pre-clinical studies, Amicus improved its properties to maximize its effect on Parkinson's disease.
- MJFF funded pre-clinical study of the optimized compound, AT3375, in 2010.
- In 2013, Biogen Idec signed on to partner with Amicus on their development of drugs to heighten GCase activity. This investment was made possible by the foundation built through MJFF support.
- The protein alpha-synuclein clumps in the cells of people with Parkinson's, leading to cell death.
- Proteostasis Therapeutics is developing a drug to increase the degradation rate of aggregation-prone proteins such as alpha-synuclein by inhibiting an enzyme that plays a role in the process.
- MJFF funded pre-clinical work to develop a chemical compound to target this enzyme, Usp14.
- In 2013, Proteostasis announced a partnership with Biogen Idec to continue development of Usp14 inhibitors for treatment of Parkinson's disease and other diseases marked by protein aggregates, such as Alzheimer's disease.
- MJFF funded biotech ProteoTech in 2006 to identify small molecule compounds that could disrupt alpha-synuclein aggregates and/or protect against Lewy body formation (including potential neuroprotective effect).
- ProteoTech tested compounds in both cell and pre-clinical models of Parkinson's disease. The company collaborated with Dr. Benjamin Wolozin (Boston University) and Eliezer Masliah (UCSD) on these models, respectively.
- MJFF provided approximately four years of funding to ProteoTech, until October 2009, and results were promising.
ProteoTech and Avid Radiopharmaceuticals collaborated to develop compounds for radiotracers to detect Lewy bodies in the brain, which would be seen via a PET scan, as a diagnostic tool for Parkinson's disease.
- They secured a joint grant from MJFF in 2009.
- Avid has continued to pursue this project on their own, via continued MJFF funding.
- ProteoTech secured a deal with GSK in late 2011 to advance their alpha-synuclein therapeutic program for PD.
- Biotech reMYND conducted pre-clinical work in Parkinson's disease with ReS9-S7, a compound that inhibits neurotoxicity associated with alpha-synuclein aggregation. However pre-clinical dose-response data to estimate the therapeutic dose was needed.
- The Foundation funded reMYND in 2009¬†to conduct these pre-clinical dose-response studies.
- reMYND was able to show that ReS9-S7 was active at low doses in models, indicating a potentially large safety window in patients.
- Following this additional pre-clinical dose-response work, reMYND entered into a partnership with Roche from 2010 to 2012 to advance their PD and Alzheimer's disease programs, and compounds with improved pharmacokinetics were developed.
- reMYND is continuing development of the compounds for PD.
- Signum focused on developing therapeutics targeting PP2A, phosphoprotein phosphatase 2A.
- Pre-clinical data on an early lead compound targeting alpha-synuclein disaggregation was generated, but further optimization was needed. Additionally, further validation of target relevance, in human brain tissue, needed to be completed.
- MJFF funded Signum to conduct these two studies in 2010.
- Collaboration with MJFF played an impactful role in Signum moving their work forward, and in 2011, GSK and Signum announced a broad-based research and development collaboration to work to screen and identify compounds that target PP2A.
- Previous studies showed people who took calcium channel blockers — a class of high blood pressure medications — had a lower incidence of Parkinson's disease.
- MJFF funded pre-clinical research at Northwestern University to study one calcium channel blocker, isradipine, in PD models.
- With positive pre-clinical results, isradipine moved to Phase II. Since the compound is already approved as a hypertension drug, it was allowed to skip Phase I safety testing.
- Due to its commercial availability, isradipine is not attractive to industry, so Foundation support was necessary to advance development.
- MJFF funded the Parkinson Study Group for the Phase II study, which showed safety and tolerability in people with Parkinson's.
- With this data made possible by Foundation funding, the Parkinson Study Group was awarded $23 million for the Phase III study by the National Institutes of Health.
- The effects on motor symptoms of oral levodopa medication can wear off before the next designated dosage time. To quickly alleviate motor symptoms when they re-emerge, Civitas Therapeutics has developed a dry-powder form of levodopa, which can be inhaled.
- MJFF funded the Phase I study to test the pharmacokinetics and safety of the formulation, called CVT-301.
- The Phase II study, also funded by the Foundation, determined a selective dose and confirmed the pharmacokinetic profile.
- With additional MJFF support, the Phase II-b study demonstrated efficacy in relief of ‚Äúoff‚ÄĚ episodes during chronic, at-home use.
- In 2013, Civitas announced they raised $38 million from investors to continue development of CVT-301 and leverage their respiratory platform for other diseases.
- The effects on motor symptoms of oral levodopa medication can wear off before the next designated dosage time. To quickly alleviate motor symptoms when they re-emerge, Cynapsus Therapeutics has developed a thin-film, under-the-tongue drug formulation.
- The drug, apomorphine (a dopamine agonist), is available for this indication but only in an injectable form.
- The Cynapsus film strip, APL-130277, aims for easier usability and a longer window of relief from motor symptoms.
- MJFF funded the Phase I study to test the pharmacokinetic profile and safety.
- In 2014 Cynapsus announced the completion of a $25 million short form prospectus financing via the public markets to progress APL-130277 further toward regulatory approval.