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Vor Biopharma says in journal that CD33-deficient HSCs can successfully engraft into the bone marrow of their host

May 29, 2019 Off By BusinessWire

Preclinical study supports Vor’s approach for empowering targeted
immunotherapies through hematopoietic stem cell editing

Paper co-authored by Vor co-founder Dr. Siddhartha Mukherjee

BOSTON–(BUSINESS WIRE)–Vor
Biopharma, an immuno-oncology company pioneering engineered
hematopoietic stem cell (HSC) therapies for hematologic malignancies,
today announced a publication in the scientific journal Proceedings
of the National Academy of Sciences (PNAS) titled “Gene-Edited
Stem Cells Enable CD33-Directed Immune Therapy for Myeloid Malignancies.”
The research describes the successful editing of HSCs that are
engineered to be selectively deficient in the myeloid lineage antigen
CD33. These CD33-deficient HSCs were shown to successfully engraft into
the bone marrow of their host. Furthermore, there was evidence these
cells could functionally repopulate the hematopoietic system. When
subjected to aggressive doses and regimens of CD33-targeted
immuonotherapies in a murine model of acute myeloid leukemia (AML),
Vor-engineered HSCs were protected from depletion by the immunotherapy
while cancer cells were selectively targeted.

These newly published results are the basis for Vor’s lead product
candidate, VOR33, and outline Vor’s unique therapeutic approach. The
paper was co-authored by Vor co-founder Siddhartha Mukherjee, M.D.,
D.Phil, of Columbia University Irving Medical Center, and his team.

Vor’s approach is designed to enable broadly targeting lineage antigens,
which are attractive targets but face serious limitations, since they
are expressed on both healthy cells and cancerous cells. Currently,
targeting lineage antigens for treating hematologic malignancies
depletes the healthy blood cells of the targeted lineage, causing severe
toxicities. These toxicities have prevented the successful development
or broader use of several otherwise promising drugs. In patients,
Vor-engineered HSCs are expected to mature and differentiate into
healthy blood cells that do not display a particular lineage antigen,
therefore making that lineage antigen tumor-specific and safe to target.

The preclinical research published today suggests that VOR33 cells will
produce healthy blood cells that will not display the lineage antigen
CD33, and therefore will not be depleted by CD33-targeted therapies. The
publication further indicates that this approach minimizes on-target
toxicities and maximizes the potency of lineage-targeted
immunotherapies, including antibody-drug conjugates, bispecific
antibodies, and chimeric antigen receptor (CAR) T cells.

“We are hoping to protect the patient’s immune system from damage during
targeted immunotherapy treatment. This approach has the potential to
transform the use of immunotherapies in hematologic diseases by enabling
the use of highly potent drugs, improving dosing, and fundamentally
changing the treatment paradigm. The novelty of the strategy is that
rather than focus only on the cancer, we are making the host – the
patient – resistant to the therapy, so that the cancer remains
vulnerable. This strategy has never been attempted in cancer,” said Dr.
Mukherjee. “This preclinical study demonstrates that Vor’s technology
can clear leukemia and repopulate healthy hematopoietic cell populations
through the use of engineered HSCs combined with a CAR-T or an
antibody-drug conjugate (ADC) or a range of other targeted immunotherapy
approaches. Remarkably, we saw that it was also possible to use a CAR-T
and an ADC in combination without untoward myelosuppression. This
research gives us great hope as we advance toward the clinic with VOR33
and look to expand our novel approach into other cancers.”

In February 2019, Vor announced the completion of a $42 million Series A
financing round led by 5AM Ventures and RA Capital to advance its lead
candidate for the treatment of AML towards the clinic, and to further
build its pipeline to treat hematologic malignancies. In November 2018,
Vor announced that the United States Patent and Trademark Office issued
U.S. Patent No. 10,137,155, which covers compositions and methods
related to using modified HSCs to enable targeted immunotherapies. This
patent, the first of its kind and foundational for the field,
established Vor as the pioneer in developing modified HSC therapies to
enable targeted immunotherapy. Subsequent to this patent’s initial
filing, additional laboratories successfully replicated key aspects
underlying the technology.

About VOR33
Vor’s lead product candidate, VOR33, is designed
to produce healthy blood cells that lack CD33, potentially protecting
them from the toxic effects of CD33-targeted immunotherapies. CD33 is a
myeloid lineage antigen that is present in the majority of acute myeloid
leukemias (AML) but is also expressed abundantly on normal myeloid
cells. Depletion of normal myeloid progenitor cells during treatment for
AML limits the dosage and duration of CD33-targeted therapies. By
empowering CD33-targeted therapy, VOR33 has the potential to overcome
current limitations.

About Vor Biopharma
Vor
Biopharma is taking a fundamentally novel approach to treat cancer
by developing engineered hematopoietic stem cells (HSCs). Vor’s
engineered HSCs are designed to generate healthy, functional blood cells
that lack the binding site of lineage antigen-targeted therapies.
Removal of the binding site protects these HSCs from depletion by
lineage antigen-targeted immunotherapies.

Vor’s platform is broad and could potentially be used to vastly improve
the therapeutic window of several lineage antigen-targeted therapies,
such as antibody drug conjugates (ADCs), bispecific antibodies, and
chimeric antigen receptor T cells (CAR-Ts). This technology platform is
covered by broad intellectual property exclusively licensed from
Columbia University, as well as Vor-owned intellectual property.
Co-founded by PureTech Health (LSE: PRTC) and Siddhartha Mukherjee,
M.D., D.Phil, Vor is working with some of the world’s leading
oncologists and immunologists to develop a pipeline of potentially
life-altering immunotherapies that extend beyond what is possible with
current treatment.