SQ3370, a novel investigational product that activates doxorubicin at the tumor site while minimizing systemic exposure, is the first click chemistry-based treatment to be used in humans

Initial Phase 1 data suggest more than 50 times greater exposure of doxorubicin in tumor versus plasma

No observed dose-limiting toxicity to date when SQ3370 is administered at doses up to four times higher than conventional doxorubicin

Nonclinical and clinical data support Shasqi continuing Phase 1 SQ3370 dose escalation

SAN FRANCISCO, Sept. 16, 2021 – Shasqi, a clinical-stage biotechnology company developing precision activated oncology therapeutics with its proprietary Click Activated Protodrugs Against Cancer (CAPAC™) platform, presented interim data from its Phase 1 clinical study of SQ3370 in advanced sarcomas and other solid tumors, as well as additional non-clinical data at the European Society for Medical Oncology (ESMO) Congress, being held virtually on September 16-21, 2021.

The interim Phase 1 clinical data were presented at the developmental therapeutics virtual poster session:

• Abstract Title: Early pharmacokinetic data from a Phase I study of SQ3370 (NCT04106492) in patients with advanced solid tumors provides proof-of-concept for the click chemistry-based CAPAC platform
• Presentation Number: 547P
• Virtual Poster Session Title: Developmental therapeutics
• Link to full poster details.

The non-clinical data were presented at the basic science virtual poster session:

• Abstract Title: Click Activated Protodrugs Against Cancer (CAPAC) Platform Enhances the Safety, Pharmacokinetics, and Antitumor Efficacy of Cancer Therapies in vivo
• Presentation Number: 9P
• Virtual Poster Session Title: Basic science
• Link to full poster details.

“These early data from our Phase 1 study of SQ3370 provide initial validation for our click chemistry-based platform in humans with an encouraging safety profile,” said José M. Mejía Oneto, M.D., Ph.D., Founder and CEO of Shasqi. “Cytotoxic agents remain standard of care for many cancers because they are effective at killing tumor cells. Our platform is designed to enhance the therapeutic benefit of these agents while minimizing toxicity. With this early validation of our platform, we can continue to advance SQ3370 and explore the application of our technology beyond chemotherapies to other standard of care cancer therapies with a limited therapeutic window.”

“Conventional chemotherapeutics are not tumor-specific and can lead to toxicity. In this study, which administered up to four times the standard dose of doxorubicin, we showed that SQ3370 has the potential to widen the therapeutic window and improve the safety profile when compared to standard doxorubicin or liposomal doxorubicin,” said Vivek Subbiah, M.D., Principal Investigator, Associate Professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center. “The early signs of clinical activity without dose limiting toxicities in this group of heavily pretreated patients, some of whom have progressed through standard doxorubicin and other chemotherapies, are encouraging. As the study advances, we will further evaluate the safety and efficacy of higher doses of SQ3370.”

The interim Phase 1 results of the first-in-human, dose escalation study of SQ3370 in patients with advanced solid tumors that are refractory/relapsed following or otherwise ineligible for standard of care therapy, were presented in poster format at ESMO 2021.

Key study findings include:

• All nine patients received at least one cycle of SQ3370
• Eight out of nine patients had metastatic disease
• Escalating doses ranged from 0.38x to 4x the molar equivalent of conventional doxorubicin
• Nonclinical and clinical pharmacokinetics (PK) data are consistent, demonstrating more than 50 times higher exposure of doxorubicin in tumor versus plasma
• No dose-limiting toxicities (DLT’s) have been observed
• The most common treatment emergent adverse events reported were nausea, fatigue, constipation and pyrexia
• Five out of eight evaluable patients had a best response of stable disease, including patients who progressed on prior doxorubicin or other prior systemic therapies
• Maximum tolerated dose has not yet been reached
• SQ3370 dose escalation is ongoing

Non-clinical results on the safety, PK, and antitumor efficacy of Click Activated Protodrugs Against Cancer (CAPAC) Platform in animal models were presented in poster format at ESMO 2021.

Key findings included:

• GLP study in canine models showed that the highest non-severely toxic dose (HNSTD) of SQ3370 was 8.95 mg/kg/cycle. Side effects were dose-dependent and reversible with no evidence of cardiotoxicity
• Rat PK modeling shows that doxorubicin exposure in the tumor is >300x higher than plasma
• SQ3370 murine models showed antitumor efficacy in multiple tumor types both in injected and non-injected lesions (abscopal effect).

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