Principal Scientist, Drug Substance

This range is provided by Sionna Therapeutics. Your actual pay will be based on your skills and experience — talk with your recruiter to learn more.

$/yr - $/yr

Sionna Therapeutics is a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for CF by developing novel medicines that normalize the function of the CFTR protein. Sionna’s goal is to deliver differentiated medicines for people living with CF that can restore their CFTR function to as close to normal as possible by directly stabilizing CFTR’s nucleotide‑binding domain 1 (NBD1), which the company believes is central to potentially unlocking meaningful improvements in clinical outcomes and quality of life for people with CF.

Leveraging over a decade of the co‑founders’ extensive research on NBD1, the company is advancing a pipeline of novel small molecules engineered to correct the defects caused by the F508del genetic mutation, which resides in NBD
1. Sionna is also developing a portfolio of complementary CFTR modulators that are designed to work synergistically with its NBD1 stabilizers to improve CFTR function.

Sionna Therapeutics is seeking a Principal Scientist to join the CMC Drug Substance group and provide technical leadership in drug substance development and manufacturing. The individual will be a hands‑on expert in modern synthetic methodology with demonstrated success in small molecule process R&D, route development, and optimization. Willingness and ability to travel occasionally (both domestic and international) to manage partner CDMOs is required.

• Design, develop, and optimize robust, cost‑effective synthetic routes to drug substance, drug substance intermediates and starting materials, with a focus on step reduction, convergence, scalability, efficiency and sustainability.
• Provide subject‑matter expertise in synthetic organic chemistry and process development to support programs from preclinical through registration.
• Contribute to the development and execution of control strategies (RSM, Impurities etc.), in alignment with global regulatory expectations.
• Support the qualification, technical oversight, and ongoing management of CDMOs manufacturing and releasing Sionna products.
• Lead and support manufacturing campaigns for Sionna products at external CDMOs.
• Participate in technical transfers, process troubleshooting, and manufacturing investigations at partner sites.
• Contribute to Quality‑by‑Design (QbD) activities for late‑stage development, including risk assessments, identification of critical quality attributes (CQAs), and establishment of control strategies.
• Support process engineering, scale‑up, and process safety studies in collaboration with internal and external experts.
• Assist with analytical method development, qualification, and validation strategies as they relate to stage appropriate drug substance development and manufacturing.
• Author and/or technically review in‑process and release specifications, analytical methods, stability protocols, and master batch records.
• Contribute to the preparation and technical review of CMC sections of regulatory submissions for US and ex‑US filings.
• Ensure activities are aligned with relevant regulatory guidance (e.g., ICH Q7, ICH Q11).
• Work closely with internal stakeholders including Discovery, Analytical Chemistry, Quality, Regulatory CMC, and Clinical teams.
• Collaborate effectively with external consultants and manufacturing partners to ensure alignment on technical and program objectives.

• PhD in Organic Chemistry or relevant discipline with 5+ years of small molecule drug substance and development experience, or MS with 10+ years of relevant experience.
• Demonstrated experience in novel route design, development, and optimization for small molecule Starting Materials.
• Hands‑on experience supporting or leading CDMO execution and release of kilogram‑scale batches.
• Strong technical problem‑solving skills with the ability to work independently on complex chemistry challenges.
• Working knowledge of regulatory CMC requirements and Regulatory guidance (ICH).
• Experience collaborating across CMC‑related functions such as Quality, Regulatory, and Clinical.
• Excellent written and verbal communication skills, with the ability to clearly convey technical concepts to diverse audiences.
• Strong organizational skills with the ability to prioritize duties and manage multiple projects with limited supervision.
• Must be willing to travel domestically and internationally as required.

Mid‑Senior level

Full‑time

Science, Manufacturing, and Research

Biotechnology and Pharmaceutical Manufacturing

Referrals increase your chances of interviewing at Sionna Therapeutics by 2x

• Medical insurance
• Vision insurance
• 401(k)
• Paid paternity leave
• Paid maternity leave
• Disability insurance

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