TwoStep Therapeutics Announces Oversubscribed $62.5 Million Series A Financing and FDA Clearance of IND for First-in-Class Peptide-Drug Conjugate

• Series A financing led by Insight Partners and Medical Excellence Capital, with M Ventures and Pfizer Ventures joining as co-lead investors, alongside existing investors, NFX and 2048 Ventures

• FDA IND clearance enables TwoStep to initiate a first-in-human Phase 1 trial of lead peptide-drug conjugate program TS-104

SAN CARLOS, Calif.--(BUSINESS WIRE)--TwoStep Therapeutics, a biotechnology company developing multi-specific targeted therapies for solid tumors, today announced an oversubscribed $62.5 million Series A financing and clearance by the U.S. Food and Drug Administration (FDA) of the Investigational New Drug (IND) application for TS-104, the company’s lead multi-specific peptide-drug conjugate. The IND clearance enables TwoStep to initiate a first-in-human Phase 1 clinical trial of TS-104, with patient enrollment expected to begin later this year.

The $62.5 million Series A was led by Insight Partners and Medical Excellence Capital, with M Ventures (the strategic, corporate venture capital arm of Merck KGaA, Darmstadt, Germany) and Pfizer Ventures joining as co-lead investors, alongside existing investors, NFX and 2048 Ventures. Additional investors also participated, including Stanford University, where the foundational science behind TwoStep was developed before the company launched in 2024. TwoStep was co-founded by Chief Executive Officer Caitlyn Miller, PhD, in collaboration with three faculty from Stanford University: Jennifer Cochran, Nobel laureate Carolyn Bertozzi, and Ronald Levy. The Series A financing brings TwoStep’s total capital raised to $71.2 million.

“This financing, together with FDA clearance of the IND, marks an important inflection point for TwoStep and positions us to advance TS-104, our lead peptide-drug conjugate, through Phase 1 clinical development in oncology. This trial will provide the first clinical evaluation of the multi-specific targeting approach at the heart of TwoStep and begin to assess its potential to broaden the reach of targeted therapies,” said Caitlyn Miller, PhD, Co-Founder and Chief Executive Officer of TwoStep Therapeutics. “Beyond TS-104, the proceeds will enable us to advance our radioligand program and expand into next-gen peptide conjugates.”

Most tumor-targeted therapies depend on high and relatively uniform expression of a single cell-surface target. In solid tumors, however, target expression can vary substantially across tumor types, between patients, and even among cells within the same tumor. This heterogeneity can restrict the addressable patient population, complicate patient selection, and allow target-low or target-negative tumor cells to escape treatment.

Rather than relying on a single target, TwoStep uses a polyspecific integrin-binding peptide (PIP) as the targeting component of its therapies. PIP is a small, synthetic peptide that targets five tumor-associated integrins expressed across a broad range of solid tumors. By engaging multiple targets rather than depending on high expression of a single antigen, PIP is designed to provide broader and more consistent tumor recognition across heterogeneous tumors. Its small size, rapid internalization, and flexible conjugation chemistry also provide attractive properties for targeted drug delivery, including the ability to pair the same targeting scaffold with different therapeutic payloads. TwoStep is leveraging this modular architecture to build a pipeline spanning peptide-drug conjugates and radioligand therapies. The company’s lead program, TS-104, couples PIP to the clinically validated cytotoxic payload MMAE.

“TwoStep is addressing one of the central challenges in solid-tumor drug development: identifying a targeting approach that can reach meaningful numbers of patients without relying on a single, uniformly expressed tumor target,” said Matias Porras Paniagua, PhD, Vice President at Insight Partners. “By engaging multiple tumor-associated integrins through a small and rapidly internalizing targeting agent, TwoStep's approach has the potential to broaden the reach of targeted therapies across tumor types and patient populations. As TS-104 enters clinical development, we look forward to seeing that potential realized in practice.”

“MEC is proud to lead the Series A financing. TwoStep truly exemplifies the characteristics we seek in leading transformative biotechnology investments: highly differentiated science, rigorous execution, and a management team dedicated to translating innovation into meaningful clinical impact for patients. Reaching an FDA-cleared IND for TS-104 is a significant accomplishment. Moreover, the caliber of this investor syndicate reflects confidence in the company’s scientific foundation as well as its long-term potential,” said John Prufeta, Founder and General Partner of Medical Excellence Capital, LLC. “We look forward to supporting Caitlyn and the outstanding TwoStep team to build a leading precision oncology company as they advance this potentially transformational program into the clinic.”

In connection with the financing, TwoStep expanded its Board of Directors with the appointments of Matias Porras Paniagua, PhD (Insight Partners), John Prufeta (Medical Excellence Capital), Oliver Lyth, PhD (M Ventures), and Rana Al-Hallaq, PhD (Pfizer Ventures). The new directors join original Board members: Omri Amirav-Drory, PhD (NFX) and Caitlyn Miller, PhD (TwoStep).

About TwoStep Therapeutics

TwoStep Therapeutics is a biotechnology company developing a pipeline built around a unique tumor-targeting polyspecific integrin-binding peptide (PIP) that can selectively bind several targets that are highly expressed on solid tumors. This multi-targeting feature enables the agent’s broad applicability to a wide range of tumor types and patient populations, overcoming the limitations of single-antigen targeting approaches. The company has leveraged this technology to create a pipeline of targeted cancer therapies for cytotoxic drug delivery and radioligand therapy.

More information: https://twosteptx.com/