Our Investment in TwoStep Therapeutics

Solid Tumor Penetration Remains a Challenge

Despite recent advancements, the potential of targeted therapies for solid tumors remains limited. Patients need more effective and less toxic targeted treatments for cancer. This is particularly true for solid tumors, which represent 90% of all cancer types. 

Some of the current limitations are due to the scarcity of extracellular targets that are highly expressed in solid tumors but minimally or not at all in healthy tissues. Most approved tumor-targeting treatments are effective only for specific subsets of solid tumors, rather than broadly across different types. 

In addition, while Antibody Drug Conjugates (ADCs) have gained significant attention recently, with almost 76 ADC deals made in 2023, these molecules present certain challenges due to complex manufacturing, poor tumor penetration, and currently limited applicability across diverse solid tumor types. 

This situation highlights a significant unmet need for more effective, broadly targeted treatments for cancer, which we believe TwoStep Therapeutics is addressing. 

A Novel Technology that Targets Cancer Broadly

TwoStep Therapeutics leverages a unique and modular polyspecific integrin-binding peptide (PIP) to mediate selectively delivery to virtually any solid tumor. The PIP targets multiple integrin receptors that are both overexpressed in cancer cells and conformationally differentiated compared to those found in healthy tissue. 

TwoStep then exploits integrins not as direct therapeutic targets (aka integrin antagonist) but rather as validated tumor-associated antigens to selectively deliver antitumor agents. This approach of leveraging integrins as targets for cargo delivery is gaining traction – Pfizer/Seagen currently has an ADC in phase 3 clinical trials that targets the β6 subunit of the αvβ6 integrin, which is one of the five tumor-associated integrins that TwoStep’s agent binds to.

The beauty of the technology is in its modularity. The technology offers high versatility and applicability across multiple therapeutic modalities and indications. TwoStep’s PIP technology can carry diverse payloads, ranging from small molecule drugs and radionuclides to larger cargo like oligonucleotides and proteins, making this a very powerful and attractive tool. 

The Right Leadership to Develop the Technology

We were impressed with TwoStep CEO Caitlyn Miller, Ph.D. from our first meeting. She is driven by a big vision: to develop PIP technology as the new gold standard of tumor-target therapy–yet she understands how to build the stepwise milestones necessary to achieve this vision.

Caitlyn earned her Ph.D. in Bioengineering from Stanford University under the guidance of Professors Carolyn Bertozzi, Jennifer Cochran, and Ron Levy, who are also co-founders of the company. This provides the company with unique insights from their combined expertise in chemical biology, protein engineering, and oncology.

Throughout the diligence process, Caitlyn demonstrated a deep fluency of the subject matter and the milestones needed for the multiple programs that TwoStep will develop. She is highly thoughtful in all interactions and substantiates her statements with data.

Our Thesis in Delivery Technology

We think now is the perfect time to bring this technology to the market. Tumor-targeting therapeutics have only begun to transform the oncology treatment landscape, and there is clearly a growing appetite for this modality. 

We are proud to join other investors, including NFX and Alexandria Venture Investments, in supporting TwoStep Therapeutics on their journey.

Learn more about TwoStep Therapeutics by reading Endpoints or BioSpace or by following CEO Caitlyn Miller, Ph.D. on LinkedIn or on their website.