9 December 2024
PureTech
Health plc
PureTech Presents Data for
LYT-200 (anti-galectin-9 monoclonal antibody) for
Relapsed/Refractory AML/MDS at the 2024 ASH Annual
Meeting
LYT-200 is generally safe
and well-tolerated as a single agent as well as in combination with
standard-of-care venetoclax and hypomethylating
agents
LYT-200 demonstrates
clinical benefit as a single agent, with two partial responses and
59% of evaluable patients achieving stable disease or
better
In combination, two complete
responses were seen and 80% of evaluable patients achieved stable
disease or better[1]
Data support LYT-200 as a
potential first-line treatment for AML/MDS
patients
PureTech Health plc
(Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the
"Company"), a clinical-stage biotherapeutics company dedicated
to changing the lives of patients with devastating diseases,
presented data from the dose escalation phase of its ongoing Phase
1b trial evaluating LYT-200, a first-in-class anti-galectin-9
monoclonal antibody, in patients with relapsed or refractory acute
myeloid leukemia (AML) and myelodysplastic syndromes (MDS) at the
2024 American Society of Hematology (ASH) Annual Meeting in San
Diego, California.
LYT-200 is currently being evaluated
both as a monotherapy and in combination with the standard-of-care
venetoclax and hypomethylating agents (HMA) for patients whose
disease is relapsed/refractory to at least one line of prior
treatment. It targets galectin-9, a glycan-binding protein that is
significantly upregulated in AML and MDS and plays a key role in
disease development, progression, immune interference and drug
resistance. Initial results show a favorable safety profile across
both arms and all dose levels with no dose limiting toxicities, as
well as evidence of response, hematological improvement and
sustained disease management.
"Relapsed/refractory acute myeloid
leukemia is one of the most dire cancer diagnoses, with 50% of
patients non-responsive to or relapsing after initial treatment and
a median survival time of less than six months,[2]" said Luba Greenwood, J.D.,
Entrepreneur-in-Residence at PureTech who is leading the Gallop
Oncology work. "We are encouraged to see that LYT-200 achieved
responses as well as long-term disease stabilization in heavily
pre-treated patients, and we look forward to progressing LYT-200 as
a critical therapeutic option with the potential to treat most AML
patients."
In the monotherapy arm, patients
received LYT-200 at five dose levels (2.0 mg/kg to 16.0 mg/kg).
Across all dose levels, LYT-200 induced clinical benefit and
responses in heavily pre-treated, relapsed/refractory AML/MDS
patients, even in those with complex cytogenetics and mutations
such as KRAS, NRAS, BRAF as well as patients previously fully
refractory to standard of care. Out of 22 evaluable patients who
received monotherapy, 59% achieved stable disease or better with
two partial responses. The mean duration on treatment is greater
than two months, which exceeds the standard overall survival of
approximately 1.7 months in venetoclax/HMA-refractory
patients.[3]
When administered in combination with
venetoclax/HMA, results demonstrate that LYT-200 may enhance the
efficacy of standard-of-care therapies, even in relapsed or
refractory patients. In the combination arm, patients received
LYT-200 across three dose levels (4.0 mg/kg to 12.0 mg/kg) with
venetoclax/HMA. Out of 15 evaluable patients who received
combination therapy, 80% achieved stable disease or better, with
two experiencing complete responses and one patient achieving a
morphologic leukemia free state (MLFS).1 The combination
regimen has also demonstrated clinical benefit in patients with
KRAS/NRAS mutations and the mean duration on treatment up until the
point of data cut-off is greater than two months.
"Galectin-9 is an essential driver of
both disease proliferation and immune suppression in AML that has
not yet been addressed therapeutically," said Aleksandra Filipovic,
M.D., Ph.D., Head of Oncology at PureTech. "LYT-200 represents a
novel approach for treating AML via a two-gear mode of action that
kills cancer cells directly via apoptosis and DNA damage, as well
as by re-activating central anti-cancer effectors of the immune
system. We are excited by these Phase 1 data that demonstrate the
transformative potential of this dual mechanism of LYT-200, both as
a single agent and in combination with existing standard-of-care
treatments."
Pharmacodynamic assessments of
treated patients, using gene and protein analyses of patient cells,
validate the LYT-200 dual mode of action, and reveal AML cellular
pathways as well as specific immune cell types which may be most
critical for response.
Based on these data, LYT-200 will
continue development in relapsed/refractory AML/MDS towards a Phase
2 clinical trial. PureTech previously announced that it intends to
advance LYT-200 via its Founded Entity, Gallop Oncology.
About LYT-200
LYT-200 is a fully human IgG4
monoclonal antibody targeting a foundational oncogenic and
immunosuppressive protein, galectin-9, for the potential treatment
of hematological malignancies and locally advanced metastatic solid
tumors, including head and neck cancers, with otherwise poor
survival rates. A wide variety of preclinical data support the
potential clinical efficacy of LYT-200 and the importance of
galectin-9 as a target and suggest a potential opportunity for
biomarker development. PureTech has presented data
demonstrating high expression of galectin-9 across various solid
tumor types and blood cancers and has found that, in several
cancers, galectin-9 levels correlate with shorter time to disease
relapse and poor survival. Preclinical work also demonstrates
single mechanistic and anti-tumor efficacy of LYT-200 in multiple
animal and patient-derived tumor cell models. For example, LYT-200
outperforms anti-PD-1 in preclinical models as a single agent.
LYT-200 also synergizes with anti-PD-1 in activating CD4 and CD8 T
cells in in vivo cancer
models. LYT-200 is currently being evaluated in two ongoing
Phase 1/2 adaptive design trials for the potential treatment of
AML/MDS and head and neck cancers.
About PureTech Health
PureTech is a clinical-stage
biotherapeutics company dedicated to giving life to new classes of
medicine to change the lives of patients with devastating diseases.
The Company has created a broad and deep pipeline through its
experienced research and development team and its extensive network
of scientists, clinicians and industry leaders that is being
advanced both internally and through its Founded
Entities. PureTech's R&D engine has resulted in the development
of 29 therapeutics and therapeutic candidates, including three that
have been approved by the U.S. Food and Drug Administration. A
number of these programs are being advanced by PureTech or its
Founded Entities in various indications and stages of clinical
development, including registration-enabling studies. All of the
underlying programs and platforms that resulted in this pipeline of
therapeutic candidates were initially identified or discovered and
then advanced by the PureTech team through key validation
points.
For more information,
visit www.puretechhealth.com or
connect with us on X (formerly Twitter)
@puretechh.
Cautionary Note Regarding Forward-Looking
Statements
This press release contains
statements that are or may be forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995.
All statements contained in this press release that do not relate
to matters of historical fact should be considered forward-looking
statements, including without limitation those related to
development plans for LYT-200, potential benefits to patients, and
our future prospects, developments and strategies. The
forward-looking statements are based on current expectations and
are subject to known and unknown risks, uncertainties and other
important factors that could cause actual results, performance and
achievements to differ materially from current expectations,
including, but not limited to, those risks, uncertainties and other
important factors described under the caption "Risk Factors" in our
Annual Report on Form 20-F for the year ended December 31,
2023, filed with the SEC and in our other regulatory
filings. These forward-looking statements are based on assumptions
regarding the present and future business strategies of the Company
and the environment in which it will operate in the future. Each
forward-looking statement speaks only as at the date of this press
release. Except as required by law and regulatory requirements, we
disclaim any obligation to update or revise these forward-looking
statements, whether as a result of new information, future events
or otherwise.
Contact:
PureTech
Public Relations
publicrelations@puretechhealth.com
Investor Relations
IR@puretechhealth.com
UK/EU Media
Ben Atwell, Rob
Winder
+44 (0) 20 3727 1000
puretech@fticonsulting.com
US
Media
Justin Chen
+1-609-578-7230
jchen@tenbridgecommunications.com
