Kleo: small molecule immuno-oncology

How Kleo's small molecules mimic or enhance antibodies for immuno-oncology

Kleo Pharmaceuticals Inc. is tapping small molecules' advantages over biologics by synthesizing compounds that mimic or modify the functions of antibodies as cancer immunotherapies.

The company spun out of Yale University in 2015 with IP developed in the lab of co-founder David Spiegel, a professor of chemistry and pharmacology who is the company’s chief scientific adviser.

Kleo CEO Doug Manion, former SVP and head of specialty development at Bristol-Myers Squibb Co., said the start-up's three platforms -- ARMs, SyAMs and MATEs -- are based on the premise that synthetic small molecules can carry out the same functions as biologics: antigen attachment and host immune cell activation. And because of their smaller size, Kleo's products should have better tissue penetration than biologics, which is an advantage for treating solid tumors.

The company's ARMs (Antibody Recruiting Molecules) are synthetic peptides or small molecules with two heads, one each for antigen binding and antibody binding, connected by a tunable linker. The molecules "basically convert any antibody into one that recognizes a specific tumor," Manion said.

SyAMs (Synthetic Antibody Mimics) are similarly bifunctional synthetic peptides or small molecules, with one end that binds an antigen and another that binds and activates immune cells such as T and NK cells. SyAMS are therefore directly comparable to T cell-engager bispecifics, he said.

MATEs (Monoclonal Antibody Therapy Enhancers) are conceptually similar to antibody-drug conjugates (ADCs). But instead of attaching a cytotoxin to a mAb to directly kill cancer cells, Kleo attaches small molecules that enhance or grant the mAb new functions -- for example, the ability to target CD3 and activate cytotoxic T cells -- to kill cancer cells indirectly via engagement with immune cells.

While Kleo is developing its platforms in tandem, ARMs, which is in proof-of-concept (POC) testing in animals, is the most advanced. Manion said the company is validating all three platforms with CD38, a marker for multiple myeloma (MM) and other hematologic malignancies, as the target.

In partnership with PeptiDream Inc., Kleo is also identifying and optimizing macrocyclic/constrained peptides for development as ARMs or SyAMs.

Kleo plans to approach pharma companies to discuss partnerships once it has validated one of the platforms. Manion added: "We think that the MATE platform is going to be particularly attractive to makers of existing monoclonals," because the platform complements mAb therapies and companies are pursuing next-generation mAbs.

Kleo hopes to have its first product in the clinic by 1H20. Manion said the product would likely be an ARM and targeting CD38, but might come form the SyAM or MATEs platforms instead. He declined to disclose a lead indication.

The company has raised $34 million to date, including a $21 million series B round in November. Manion declined to disclose how long the funding would last, but said it would support Kleo through at least a human POC trial of its first asset.


Kleo Pharmaceuticals Inc., New Haven, Conn.

Technology: Small molecules that mimic or modify antibody functions

Disease focus: Cancer

Clinical status: Preclinical

Founded: 2015 by David Spiegel and Roy Prieb

University collaborators: Yale University and Magna Graecia University

Corporate partners: PeptiDream Inc.

Number of employees: 17

Funds raised: $34 million

Investors: Biohaven Pharmaceutical Holding Co. Ltd., PeptiDream Inc., Connecticut Innovations and Yale University

CEO: Doug Manion

Patents: Undisclosed

Companies and Institutions Mentioned

Bristol-Myers Squibb Co. (NYSE:BMY), New York, N.Y.

Kleo Pharmaceuticals Inc., New Haven, Conn.

PeptiDream Inc. (Tokyo:4587), Tokyo, Japan

Yale University, New Haven, Conn.

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