Page 15 - 2021 Spring CMTA Report - Special Research Edition

The CMTA has acquired and characterized best-in-class Confidential Partner B: The testing resource is
mouse and rat models of CMT1A so we know when to “therapy agnostic” and can be used to evaluate gene
test a drug, for how long and what signifiers of therapy approaches as well as ASOs, biologicals and
improvement need to be measured. Currently, six models small molecules. Our first alliance partner in this area has
are well characterized and available, representing four been evaluating the delivery of its gene modifying system,
different types of CMT. Expert contract research packaged inside an AAV virus, to nerves in CMT1A animals.
organizations have been engaged to perform the testing The gene localization studies are still in progress, and if
under CMTA direction, and our agreement structure lowers delivery is sufficiently effective, this will be followed in
common barriers to entry such as confidentiality, retention 2021 by a complete series of preclinical efficacy studies to
of intellectual property and long-term financial commitment. determine if the approach can correct the CMT1A defect
In addition to the validated CMT animal models, the CMTA and restore normal function in the animals.
and the New York Stem Cell Foundation (NYSCF) have put Confidential Partner C is developing a novel biological
together a collection of patient-derived stem cell lines for approach to treat CMT and asked for our help in evaluating
CMT, including CMT1A. These cell lines give companies its candidate in both Type 1 (CMT1A) and Type 2 models.
the ability to test therapies on patients’ own genes, the first These studies showed promising results in both models,
step to enabling a personalized medicine strategy. and together we are pursuing studies to determine the site
A number of companies are engaged in testing for CMT1A of action of the candidate therapeutic, which may not be
with us. Of the four CMT types currently in preclinical directly in the nerve but at the junction of nerve and
testing, CMT1A has attracted the highest interest due to muscle. Additional studies are being discussed that would
its prominence in the CMT patient population. All therapy examine further biomarker elevation in both models and
modalities are represented in the current portfolio of assess the survival of peripheral nerve in the completed
alliance activity, from small molecules to biologicals to studies.
genetic modifiers. InFlectis BioScience, a French startup company, is
Sanofi was our first alliance partner for CMT1A and in working to develop a new approach to CMT1B and
2020 evaluated small molecules that came from this joint CMT1A. Sponsored research studies have been performed
program as potential new alliance partners have expressed in the CMTA STAR consortium to assess drug effects in
interest in acquiring them. In addition, Sanofi has asked the both animal models and InFlectis is currently raising funds
CMTA to lead testing of a new small-molecule approach for clinical trial testing of the molecule in patients.
that has been advancing for a different but related disease Pharnext, a French company, is developing a combination
area. In 2020, Sanofi restructured, closing its neuroscience of several known drugs for the treatment of CMT1A,
unit in Boston. which when given together may be effective at slowing
Ionis Pharmaceuticals was the first partner to progression of the disease. The small molecule
demonstrate that a genetic modifier of the PMP22 gene combination showed benefit in early clinical trials, and
(anti-sense oligonucleotides or ASOs) could effectively regulatory authorities have asked the company for an
repair CMT1A defects in animal models of the disease. additional, expanded trial using the highest proposed dose
Since then, Ionis has been working to solve a generally combination. The company has raised additional funds for
understood limitation of its technology–the delivery of the this clinical trial extension, and is currently continuing to
ASOs to the target Schwann cells. They have acquired from dose patients. Results are expected in the second quarter
us CMT1A stem cell lines in the NYSCF repository for use in of 2021.
testing different approaches to enhance ASOs delivery. We The CMTA has supported Pharnext with patient advocacy
are awaiting results from this work, which would allow efforts and is providing biomarkers in preparation for Phase
its CMT1A effort to advance if successful. III clinical trials.
Regenacy owns a drug candidate that has been in human
testing for a different disease but may have value in
treating CMT. Regenacy accessed our testing resource to
evaluate the candidate in several CMT types, including
CMT1A. The results of the evaluations were mixed, and
Regenacy is evaluating which efforts merit further study
via an external collaboration to test activity in cell-based
models of CMT.
Confidential Partner A owns a drug candidate derived
from a program at a major pharmaceutical company.
Based on known evidence of the drug target’s possible
role in CMT disorders, the company pursued evaluation
in both Type 1 (CMT1A) and Type 2 CMT animal models.
We provided partial evidence of effect in CMT1A, and
very detailed data that the drug’s effect was primarily on
sensory, not motor, nerves. From this data, the company
concluded that the benefit of using this drug class in
CMT therapy was not sufficiently compelling and the effort
was terminated.

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