TwoStep Therapeutics Secures $62.5 Million Series A and FDA Clearance for TS-104 Phase 1 Trial
TwoStep Therapeutics, a biotechnology company developing multi-specific targeted therapies for solid tumors, has announced two significant milestones that mark the company’s transition into clinical development. The company has closed an oversubscribed $62.5 million Series A financing and received clearance from the U.S. Food and Drug Administration (FDA) for the Investigational New Drug (IND) application for TS-104, its lead multi-specific peptide-drug conjugate (PDC).
The FDA clearance allows TwoStep Therapeutics to advance TS-104 into a first-in-human Phase 1 clinical trial. Patient enrollment is expected to begin later this year, establishing the company’s lead program as it seeks to develop a new approach to targeted treatment for patients with solid tumors.
The financing and regulatory milestone provide TwoStep with resources to progress TS-104 through early clinical development while simultaneously expanding its broader pipeline. The company plans to use a portion of the proceeds to advance its radioligand program and develop next-generation peptide conjugates.
$62.5 Million Financing Supports Clinical Expansion
TwoStep Therapeutics’ Series A financing 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 participating as co-lead investors.
Existing investors NFX and 2048 Ventures also participated in the financing, along with additional investors including Stanford University. The inclusion of Stanford is notable because the foundational scientific research underlying TwoStep’s technology originated at the university before the company was launched in 2024.
The company was co-founded by Chief Executive Officer Caitlyn Miller, PhD, together with Stanford faculty members Jennifer Cochran, Nobel laureate Carolyn Bertozzi, and Ronald Levy.
With the completion of the Series A round, TwoStep Therapeutics has now raised a total of $71.2 million in capital. The oversubscribed financing reflects significant investor interest in the company’s multi-specific targeting strategy and its potential application across solid tumors.
“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,” said Caitlyn Miller, PhD, Co-Founder and Chief Executive Officer of TwoStep Therapeutics.
Miller added that the upcoming clinical trial will provide the first clinical evaluation of the company’s multi-specific targeting strategy and could help determine whether the approach can expand the reach of targeted cancer therapies. Beyond TS-104, the financing is expected to support development of the company’s radioligand program and next-generation peptide conjugates.
Addressing Tumor Heterogeneity
A major challenge in the development of targeted cancer therapies is the variability of molecular targets within solid tumors. Many targeted therapies are designed to recognize a particular cell-surface antigen and depend on that target being expressed at sufficiently high levels across a patient’s cancer cells.
However, solid tumors can be highly heterogeneous. Target expression can differ between tumor types, between individual patients and even among different cancer cells within the same tumor. This variability can reduce the number of patients who are eligible for a particular targeted therapy and may create opportunities for tumor cells with low or absent target expression to evade treatment.
TwoStep Therapeutics is attempting to address this limitation through a multi-specific targeting strategy. Instead of depending on a single tumor-associated target, the company’s platform uses a polyspecific integrin-binding peptide, or PIP.
PIP is a small synthetic peptide designed to recognize five tumor-associated integrins that are expressed across a broad range of solid tumors. By targeting multiple integrins rather than relying on one antigen, the company aims to improve tumor recognition across heterogeneous cancer populations.
The approach could potentially expand the addressable patient population for targeted therapies while reducing the dependence on uniform expression of a single molecular target.
Small Peptide Designed for Targeted Drug Delivery
The PIP targeting component has several characteristics that TwoStep believes could make it suitable for therapeutic delivery. The peptide is relatively small, can be internalized rapidly by target cells and has flexible conjugation chemistry.
Rapid internalization is particularly important for a peptide-drug conjugate because the targeting component must not only recognize tumor-associated targets but also facilitate delivery of the attached therapeutic payload into cancer cells.
TwoStep is using this modular architecture to develop a pipeline that extends beyond a single drug candidate. The same targeting scaffold can potentially be paired with different therapeutic payloads, allowing the company to investigate multiple approaches to tumor treatment.
The company’s development strategy currently spans peptide-drug conjugates and radioligand therapies. This platform-based approach is intended to provide flexibility as the company evaluates different therapeutic mechanisms and payloads.
TS-104 Combines PIP With MMAE
The lead program, TS-104, combines the PIP targeting scaffold with monomethyl auristatin E (MMAE), a clinically validated cytotoxic payload.
MMAE is designed to disrupt microtubule function, ultimately interfering with cancer-cell division and promoting cell death. By linking the payload to the PIP targeting component, TwoStep aims to selectively deliver the cytotoxic agent to tumor cells expressing the targeted integrins.
The company’s multi-specific strategy is intended to enable TS-104 to recognize tumor cells through several integrin targets. This differs from traditional targeted therapies that may depend heavily on the presence of one highly expressed antigen.
The ability to use a single targeting scaffold against multiple tumor-associated integrins could be particularly relevant to solid tumors, where variations in target expression can complicate the development and clinical use of precision medicines.
However, the upcoming Phase 1 study will be important for determining whether the preclinical rationale translates into meaningful clinical activity and an acceptable safety profile in humans.
First-in-Human Clinical Development
With FDA clearance of its IND application, TwoStep is preparing to begin clinical testing of TS-104. The Phase 1 trial will represent the first evaluation of the company’s multi-specific targeting technology in human patients.
As an early-stage oncology study, the trial is expected to focus primarily on establishing the safety and tolerability of TS-104 while also evaluating pharmacokinetics, appropriate dosing and preliminary evidence of antitumor activity.
The transition into human studies represents a major milestone for the company because it will provide an opportunity to assess how the PIP-based targeting strategy performs in patients with solid tumors.
The data generated during the Phase 1 program could help identify tumor types and patient populations that may be particularly suitable for subsequent clinical development.
The company expects to begin enrolling patients later this year.
Investor Confidence in the Platform
The Series A financing has attracted a broad group of investors from venture capital, pharmaceutical and academic communities.
Matias Porras Paniagua, PhD, Vice President at Insight Partners, said the company is addressing a major challenge in solid-tumor drug development: developing targeting strategies that can reach meaningful numbers of patients without depending on a single uniformly expressed target.
According to Porras Paniagua, the combination of multiple tumor-associated integrin targets with a small and rapidly internalizing targeting agent could potentially broaden the application of targeted therapies across tumor types and patient populations.
The investors’ support also provides TwoStep with the financial resources needed to move beyond proof-of-concept research and into clinical testing.
John Prufeta, Founder and General Partner of Medical Excellence Capital, said the company reflects several characteristics the firm looks for in transformative biotechnology investments, including differentiated science, execution capabilities and a focus on translating scientific innovation into clinical impact.
Prufeta also highlighted the FDA-cleared IND as a significant achievement and pointed to the strength of the investor syndicate as evidence of confidence in TwoStep’s scientific foundation and long-term potential.
Board of Directors Expanded
Alongside the Series A financing, TwoStep Therapeutics has expanded its Board of Directors with four new appointments.
The new directors are Matias Porras Paniagua, PhD, representing Insight Partners; John Prufeta of Medical Excellence Capital; Oliver Lyth, PhD, representing M Ventures; and Rana Al-Hallaq, PhD, representing Pfizer Ventures.
They join the company’s original Board members, including Omri Amirav-Drory, PhD, representing NFX, and Caitlyn Miller, PhD, representing TwoStep Therapeutics.
The expanded board brings experience spanning biotechnology investment, pharmaceutical development, venture capital and scientific research as the company enters a more advanced stage of development.
Building a Multi-Specific Oncology Pipeline
The company’s immediate priority is to advance TS-104 into and through Phase 1 clinical development. At the same time, TwoStep plans to use the Series A proceeds to broaden its pipeline beyond its lead peptide-drug conjugate.
The company is advancing a radioligand program and plans to expand its work in next-generation peptide conjugates. The modularity of its PIP targeting platform could allow different payloads and therapeutic mechanisms to be evaluated against the same underlying tumor-targeting strategy.
If successful, this approach could eventually enable TwoStep to establish a broader portfolio of targeted therapies designed to overcome some of the limitations associated with tumor heterogeneity.
For now, the FDA clearance of the TS-104 IND and the $62.5 million Series A financing provide the company with a strong foundation for its next phase of growth. As patient enrollment begins later this year, clinical data from TS-104 will offer the first opportunity to determine whether TwoStep’s multi-specific integrin-targeting strategy can deliver the selectivity, tumor penetration and therapeutic activity needed to advance targeted treatment options for patients with solid tumors.
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.