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Siamab Therapeutics Announces Publication in PLOS ONE of Positive Data from Preclinical Studies of its ST1 Antibody Therapeutic in Development for Ovarian Cancer


Findings Demonstrate Anti-Tumor Activity and a Favorable Safety
Profile of Humanized Anti-STn Antibody Drug Conjugate in Multiple
Ovarian Carcinoma Models and a Pilot Toxicology Study

Therapeutics, Inc.,
a biopharmaceutical company developing novel
glycan-targeted cancer therapeutics, today announced the publication of
positive preclinical data for its ST1 antibody drug conjugate (ADC) in
multiple models of ovarian cancer. Siamab's lead ST1 program targets
Sialyl-Tn (STn), a tumor-associated carbohydrate antigen (TACA), which
is expressed on ovarian and other solid tumors and is associated with
metastatic disease, poor prognosis, chemo-resistance, and reduced
overall survival. The paper describes study data demonstrating that
Siamab's humanized anti-STn ADC provides a novel glycan-specific
targeting mechanism for the potential treatment of ovarian carcinoma.
The data were published online in the peer-reviewed journal PLOS

"The published data continue to validate the potential for a
STn-targeted therapy in treating ovarian cancer, which today has limited
effective treatment options and poor long-term survival," said Jeff
Behrens, president and chief executive officer of Siamab. "Our growing
body of preclinical evidence with the ST1 program highlights a strong
activity profile across a range of ovarian cancer models."

Rueda, Ph.D.,
director of The Vincent Center for Reproductive
Biology at Massachusetts General Hospital, and the principal
investigator of studies described in the paper said, "This new paper
includes important recent murine patient derived xenograft (PDX)
findings that show that the compound is both effective in multiple PDX
models and well-tolerated with no target-related toxicities. The known
specificity of STn for malignant tissue in combination with the high
affinity and STn-specific selectivity of the humanized ST1 antibody
therapeutic provide a compelling rationale to evaluate ST1-ADC in
patients with STn-expressing ovarian tumors."

In the paper titled, "Humanized anti-sialyl-Tn antibodies for the
treatment of ovarian carcinoma," Siamab researchers and collaborators
report findings that show Siamab's humanized anti-STn ADC demonstrated in
cytotoxicity specific to STn-expressing ovarian cancer cell
lines and inhibited tumor growth in vivo in both cell line- and
PDX ovarian cancer mouse models. No significant weight loss or other
gross clinical changes were observed for any of the treatment groups in
these models, indicating the therapy was well tolerated by all groups.

The paper also describes additional data from a pilot toxicity study in
nonhuman primates (NHP) that demonstrates that Siamab's humanized
anti-STn ADC has a favorable safety and pharmacokinetic profile. There
were only mild monomethyl auristatin E (MMAE)-class related
hematological effects with none being attributed to the targeting of
STn. Dose concentrations in the NHP toxicity study were 12 times higher
than concentrations used in preclinical mouse models where anti-tumor
activity was observed. No weight loss or deaths occurred in the pilot
toxicity study. A histopathology review of all major organs showed no
observations linked to STn target-associated toxicity.

Ovarian cancer is the most deadly gynecologic cancer in the United
States. Despite surgical debulking and chemotherapy, the five-year
survival rate remains below 50%. Ovarian cancer has few common
targetable mutations, amplifications and/or deletions. The
identification of additional alterations in ovarian cancer is key to
developing effective, targeted therapies.

Glycosylation of proteins is one of the most abundant and diverse
post-translational modifications, with more than half of all human
proteins estimated to be glycosylated.1 Targeting an altered
glycosylation pattern specific to tumor cells may offer significant
anti-cancer benefit.

STn is expressed on a significant number of ovarian cancers, including
the well-known ovarian cancer biomarkers CA-125 (MUC16) and MUC1, and is
rarely present on normal tissue, which makes it a favorable target for
therapeutic intervention in ovarian cancer.2,3 Elevated serum
levels of STn occur in the majority of ovarian cancer patients and
correlate with lower progression-free survival and overall five-year
survival rates.4

About Siamab Therapeutics, Inc.
Siamab Therapeutics, Inc. is
a biopharmaceutical company developing novel cancer therapeutics
targeting cancer-specific carbohydrate antigens seen on multiple solid
tumors. Siamab's proprietary platform enables the rapid discovery and
development of therapeutic antibodies that bind with unprecedented
specificity and affinity to the novel class of carbohydrate antigens
present on cancer cells called tumor-associated carbohydrate antigens
(TACAs). TACAs are exciting cancer targets due to their cancer
specificity, association with a chemoresistant phenotype, and ability to
suppress immune function in solid tumors. The company's lead program,
ST1, targets Sialyl-Tn (STn), a tumor specific antigen expressed on
multiple solid tumors including ovarian, gastric, colon, prostate,
pancreatic and lung cancers. ST1 is in late-stage preclinical studies
for the treatment of solid tumors. Visit
to learn more about the company.

1. Christiansen, M. N., Chik, J., Lee, L.,
Anugraham, M. & Abrahams, J. L. Cell surface protein glycosylation in
cancer. Proteomics Dec 12, 1-46 (2013).

2. Akita, K. et al. Different levels of sialyl-Tn antigen
expressed on MUC16 in patients with endometriosis and ovarian cancer. Int.
J. Gynecol. Cancer
22, 531-8 (2012).

3. Tarp, M. A. et al. Identification of a novel cancer-specific
immunodominant glycopeptide epitope in the MUC1 tandem repeat. Glycobiology
17, 197-209 (2007).

4. Kobayashi, H., Terao, T., & Kawashima, Y. Clinical
evaluation of circulating serum sialyl Tn antigen levels in patients
with epithelial ovarian cancer. J. Clin. Oncol. 9, 983-7 (1991).

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