Quince Therapeutics, Inc. is a late-stage biotechnology company dedicated to developing innovative therapies that leverage a patient's own biology to treat rare and devastating diseases. The company's proprietary AIDE technology platform utilizes an automated process to encapsulate drugs within a patient's own red blood cells, unlocking the potential for improved safety, efficacy, and patient outcomes.

At the Core of Quince's Strategy: Addressing High Unmet Needs in Rare Diseases

Quince Therapeutics was founded in 2014 with an initial focus on developing novel therapeutic approaches for Alzheimer's and other degenerative diseases. The company's early efforts centered on small molecule protease inhibitors, including atuzaginstat (COR388) and COR588, for the treatment of neurodegenerative diseases.

In 2022, Quince underwent a significant strategic shift, initially redirecting its focus towards the development of a bone-targeting drug platform and lead compound NOV004 for rare skeletal diseases, bone fractures, and injury. However, in January 2023, the company made another pivotal decision to out-license its bone-targeting drug platform and prioritize capital resources toward expanding its development pipeline.

This strategic realignment culminated in the acquisition of EryDel in October 2023, which brought Quince its current lead asset, EryDex. This acquisition marked a transformative moment for the company, positioning it at the forefront of developing innovative therapies using autologous red blood cell delivery systems.

Quince's lead asset, EryDex, is a first-in-class therapy that encapsulates the corticosteroid dexamethasone sodium phosphate (DSP) within autologous red blood cells. EryDex is currently being evaluated in a pivotal Phase 3 clinical trial for the treatment of Ataxia-Telangiectasia (A-T), a rare and debilitating neurodegenerative disorder that primarily affects children.

A-T is a devastating condition with no approved treatments, characterized by progressive neurodegeneration, immunodeficiency, and increased cancer risk. The current standard of care relies on chronic corticosteroid administration, which is limited by severe side effects that often lead to treatment discontinuation, particularly during adolescence when growth and sexual maturation are impaired.

Quince's Innovative Approach: Harnessing the Power of a Patient's Own Red Blood Cells

Quince's proprietary AIDE technology is designed to encapsulate drugs, such as DSP, within a patient's own red blood cells. This approach offers several potential advantages over conventional drug delivery:

1. Improved Biodistribution: The encapsulated drug is designed to slowly release from the red blood cells as they traverse the body, potentially enhancing tissue distribution and targeting.

2. Altered Pharmacokinetics: The red blood cell encapsulation may prolong the drug's circulation half-life and alter its pharmacodynamic profile, potentially improving efficacy and safety.

3. Enhanced Biocompatibility: Using a patient's own red blood cells minimizes potential immunogenicity and compatibility issues.

4. Versatility: The AIDE platform is designed to be applicable to a broad range of small molecules, peptides, and biologics, opening the door to future pipeline expansion.

Pivotal Phase 3 NEAT Trial Underway in Ataxia-Telangiectasia

Quince initiated the pivotal Phase 3 NEAT (Neurologic Effects of EryDex on Subjects with A-T) clinical trial in the second quarter of 2024. The trial is being conducted under a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA), which is designed to expedite the regulatory pathway for EryDex.

The NEAT trial is a global, multicenter, randomized, double-blind, placebo-controlled study evaluating the neurological effects of EryDex in approximately 86 A-T patients aged 6 to 9 years, as well as 20 patients aged 10 years and older. The primary endpoint is the change from baseline to the last visit in the Rescored modified International Cooperative Ataxia Rating Scale (RmICARS), a validated measure of neurological function in A-T patients.

As of November 13, 2024, Quince has enrolled 32 patients across clinical sites in the U.S., Europe, and the U.K., with the majority of planned study sites now actively recruiting. The company expects to complete enrollment in the first half of 2025 and report topline results from the NEAT trial in the fourth quarter of 2025.

Valuable Insights from Prior Phase 3 ATTeST Trial

While the prior Phase 3 ATTeST (Ataxia-Telangiectasia Trial with the EryDex SysTem) trial did not meet its primary endpoint, the study provided valuable insights that are informing Quince's approach to the ongoing NEAT trial:

• The high-dose EryDex arm showed statistically significant improvements in the 6-to-9-year-old patient subgroup, the age range that typically experiences the most rapid neurological decline in A-T.

• EryDex was generally well-tolerated, with no notable safety concerns typically associated with chronic corticosteroid use, such as adrenal suppression or growth impairment.
• The company has optimized the NEAT trial design, including patient enrollment criteria and outcome measures, to build upon the learnings from ATTeST.

Strengthening the Patent Portfolio and Regulatory Positioning

In addition to the clinical progress, Quince recently announced that the U.S. Patent and Trademark Office (USPTO) has issued a Notice of Allowance for a patent application covering the method of treating patients with A-T using the company's proprietary EryDex process. This allowance, which extends into 2036, further strengthens Quince's intellectual property protection for its lead asset.

Furthermore, the FDA has granted Fast Track designation for the EryDex System for the treatment of A-T, providing opportunities for frequent interactions with the agency and potential eligibility for priority review upon completion of the NEAT trial.

Financials

As of September 30, 2024, Quince reported cash, cash equivalents, and short-term investments of $47.8 million, which the company believes will be sufficient to fund its planned operations, including the completion of the Phase 3 NEAT trial, into the first quarter of 2026.

For the most recent fiscal year (2023), Quince reported a net loss of $31.39 million. In the most recent quarter (Q3 2024), the company reported no revenue and a net loss of $5.49 million, representing a 2% increase in net loss compared to Q3 2023 ($5.35 million).

Liquidity

Quince's liquidity position remains strong, with a debt-to-equity ratio of 0.34 as of September 30, 2024. The company had $2.67 million in cash and cash equivalents, and $45.17 million in short-term investments, totaling $47.80 million in liquid assets.

As part of the EryDel acquisition in October 2023, Quince assumed an unsecured line of credit with the European Investment Bank (EIB Loan). The EIB Loan provides for maximum borrowings of €30 million through four tranches, of which only tranches A (€3 million) and B (€7 million) have been drawn as of September 30, 2024, with a total of €10 million (approximately $11.20 million) outstanding. The EIB Loan bears interest at fixed rates ranging from 7-9% per annum, and the company is required to maintain a minimum cash balance of €14.65 million (approximately $16.40 million) until the loan is repaid.

Quince's current ratio and quick ratio both stand at 9.53, indicating a strong ability to meet short-term obligations.

Market Opportunity and Pipeline Expansion

Quince has completed a patient sizing project which confirmed approximately 4,600 diagnosed A-T patients in the U.S. The global market for A-T treatment represents a potential peak commercial opportunity of more than $1 billion, based on the company's internal estimates and assumptions.

In addition to the ongoing NEAT trial in A-T, Quince has identified several other rare disease indications where chronic corticosteroid administration is a standard of care but limited by safety concerns. The company plans to explore a capital-efficient strategy, potentially through investigator-initiated studies, to evaluate the potential of EryDex in these additional rare disease settings.

Specifically, Quince intends to evaluate EryDex for the treatment of Duchenne muscular dystrophy (DMD) and plans to initiate a Phase 2 trial of EryDex in DMD in 2025.

Navigating Challenges and Setbacks with Resilience

Quince's journey has not been without its challenges. In 2022, the company encountered a clinical hold on the investigational new drug (IND) application for its former lead asset, atuzaginstat (COR388), which ultimately led to the out-licensing of that program. Additionally, the previous Phase 3 ATTeST trial in A-T did not meet its primary endpoint, though it did demonstrate positive effects in a key patient subgroup.

Despite these setbacks, Quince has demonstrated resilience and a commitment to its core mission. The company has refocused its efforts on the development of EryDex, leveraging the insights from the ATTeST trial to design a more targeted and optimized NEAT study. Quince has also taken steps to strengthen its financial position and intellectual property portfolio, positioning the company for long-term success.

Conclusion: Quince Therapeutics – Unlocking the Power of Autologous Red Blood Cells for Rare Disease Treatments

Quince Therapeutics is a late-stage biotechnology company that is pioneering the use of a patient's own red blood cells as a delivery mechanism for rare disease therapies. With its lead asset, EryDex, currently in a pivotal Phase 3 trial for the treatment of Ataxia-Telangiectasia, Quince is well-positioned to address the significant unmet need in this devastating condition.

The company's innovative AIDE technology platform, robust clinical data, strengthened patent portfolio, and solid financial position provide a strong foundation for Quince to advance EryDex and explore the potential of its approach in additional rare disease indications. As Quince continues to navigate the challenges of drug development, its unwavering commitment to unlocking the power of a patient's own biology offers hope for those living with rare and debilitating diseases.