Dogma Therapeutics Emerges from Stealth Mode and Announces Oral PCSK9 Inhibitor Program

Discovery program accelerated by a unique collaboration between
Dogma, Charles River, & Viva Biotech

CAMBRIDGE, Mass.–(BUSINESS WIRE)–The word “undruggable” has hampered pursuit of the most compelling
biological targets, drawing from established opinion that
pharmacological modulation was not possible. Scientists at Dogma
(“Dogma”) were determined to challenge this assumption.
Dogma has discovered an orally-bioavailable small molecule PCSK9
inhibitor. By strategically focusing on small molecule inhibitors, Dogma
can readily combine their compounds with current standard of care and
dramatically disrupt the health economics of PCSK9-based therapies.

Several antibody-based inhibitors emerged following the rapid
accreditation of the PCSK9 target through human genetics. However,
despite large outcome trials showing a 15-20% reduction in cardiac
events, the cost-effectiveness and wide use of antibody-based PCSK9
injectables has been questioned. Alternate approaches to PCSK9
inhibition have been stymied by the expansive binding surface targeted
by the antibodies, and to date, only indirect approaches to PCSK9
inhibition by small molecules have been reported.

Dogma has discovered small molecule inhibitors that directly bind to a
novel, cryptic binding pocket in PCSK9. Guided by dozens of
high-resolution x-ray structures of inhibitors bound to the PCSK9
protein, these molecules have been optimized to picomolar affinity. When
orally administered to dyslipidemic non-human primates, multiple Dogma
inhibitors elicit significant and robust lowering of LDL-C following
multiple weeks of administration.

We are excited to progress our first-generation oral PCSK9 inhibitor
into the clinic to understand the potential for LDL lowering with our
approach,” noted co-founder Brian Hubbard, Ph.D. “Human data with our
oral PCSK9 inhibitor will provide valuable feedback for ongoing research
and catalyze our ability to deliver this important modality to more
patients. I would like to thank our scientific partners to date –
Charles River and Viva Biotech – for their commitment to this project
and their world-class problem solving.”

Since inception, Dogma has developed a highly collaborative research
model that leverages scientific expertise across the globe. This
collaborative model was created by Charles River, a leading,
full-service drug discovery and early-stage development company, who,
with its global, integrated
drug discovery and safety assessment platform
, has worked on 85% of
drugs approved by the FDA in 2018. In this project, Charles River
scientists and project leads contributed medicinal chemistry, structural
biology and biophysics, cell biology and PK/PD expertise. “Charles River
has played an integral role in the launch and progression of Dogma with
their broad drug discovery expertise and knowledge,” noted Hubbard.

Our team is extremely proud to have worked closely with Dogma
throughout the development of its oral PCSK9 inhibitor,” said Birgit
Girshick, Corporate Executive Vice President of Global Discovery and
Safety Assessment at Charles River. “This ground-breaking project could
prove transformational in the management of hypercholesterolemia and
cardiovascular disease.”

The second key partner, Viva Biotech, is a leading structure-based,
integrated drug discovery platform company. Viva has a full spectrum of
early-stage drug discovery technologies from hit identification to
clinical candidate nomination, combined with a unique equity-for-service
model. Viva has incubated more than 30 startup biotech companies similar
to Dogma and plans to work with 100 more in the next 2 years.

It was an exceptionally rewarding experience for our team to have a
close partnership with Dogma and Charles River as we rapidly advanced
the program towards clinical study,” said Zhixiong Ye, Chief Scientific
Officer at Viva Biotech. “An orally-bioavailable small molecule PCSK9
inhibitor will greatly impact the unmet medical needs of cardiovascular

More information on the teams can be found here:

Dogma Therapeutics:
River Laboratories:

This press release contains forward-looking
statements that can generally be identified by words such as “will,” or
similar expressions. You should not place undue reliance on these
statements. Such forward-looking statements are based on our current
beliefs and expectations regarding future events, and are subject to
significant known and unknown risks and uncertainties. Should one or
more of these risks or uncertainties materialize, or should underlying
assumptions prove incorrect, actual results may vary materially from
those set forth in the forward-looking statements. This press release
does not require an update of any forward-looking statements as a result
of new information, future events or otherwise.


Michael Serrano-Wu, Ph.D.