Antibody-Drug Conjugates (ADC) & Degrader-Antibody Conjugates (DAC)
Location: Cambridge, MA (on-site)
Employment Type: Full-time, contract-to-hire (12 months), with conversion to a permanent position based on performance and business needs
Reports To: Executive Director, Translational Research & Corporate Development
Start Date: Immediate
About PineTree Therapeutics
PineTree Therapeutics is a Cambridge, MA-based biotechnology company developing novel antibody- based therapeutics, including antibody-drug conjugate (ADC) and degrader-antibody conjugate (DAC) programs. We are a small, hands-on team that values scientific rigor, speed, and ownership.
Position Summary
The Director, ADC & DAC will provide scientific and technical leadership for PineTree's antibody-drug and degrader-antibody conjugate programs, serving as the owner and single point of accountability for the end-to-end conjugate effort; from linker, payload, and conjugation strategy through candidate selection and IND-enabling development. This is an active technical leadership role. You will set the scientific direction for the conjugate effort and stay deep in the science - driving design decisions and troubleshooting the most challenging linker-payload and bioconjugation problems, rather than executing routine bench work. Payloads of interest span targeted small-molecule and classical cytotoxic modalities.
Key Responsibilities
Program Leadership
- Own the overall ADC/DAC effort and serve as the single point of accountability for PineTree''s conjugate programs.
- Define and drive the integrated linker-payload and conjugation strategy from feasibility and proof- of-concept through candidate selection and IND-enabling development.
- Contribute to program prioritization, timelines, and go/no-go decisions.
Linker, Payload & Conjugation Strategy (Design & Optimization)
- Guide selection and optimization of linkers, conjugation chemistries, attachment sites, and drug-to- antibody ratio (DAR).
- Apply deep medicinal- and bioconjugation-chemistry expertise to match payloads with appropriate linker-payload designs.
- Lead the design, structure-activity analysis, and troubleshooting of complex linker-payload constructs.
- Advise on payload-class selection, physicochemical properties, conjugate stability, and release mechanisms.
Intellectual Property & Platform Innovation
- Help PineTree build proprietary IP around linkers and conjugation approaches for future ADC and DAC programs.
- Identify novel linker/conjugation concepts that enhance intracellular payload delivery and release.
- Contribute to invention disclosures, patent filings, and freedom-to-operate assessments in collaboration with internal leadership and IP counsel.
CMC, Analytical & Translational Interface
- Partner with CMC, analytical, DMPK/toxicology, and translational colleagues to ensure conjugate designs are developable and support IND-enabling and downstream activities.
- Advise on ADC/DAC analytics (e.g., DAR and drug-load distribution, aggregation, free payload,
LC-MS, HIC), conjugate stability, and the PK/tox implications of linker-payload choices.
- Contribute conjugate-related content to scientific reports and regulatory documentation as programs advance.
Qualifications
Required
- Ph.D. in synthetic organic chemistry, medicinal chemistry, bioconjugation/chemical biology, or a related discipline (or equivalent experience).
- 10+ years of biotech/pharmaceutical experience in ADC or bioconjugate drug development, with demonstrated depth in linker-payload design and antibody conjugation.
- Proven track record advancing ADC/conjugate programs - from linker-payload design and optimization through candidate selection and/or IND-enabling development.
- Hands-on expertise in linker chemistry and conjugation methods (e.g., cysteine/lysine and site- specific conjugation, DAR control and characterization) across multiple payload classes.
- Working knowledge of payload classes, including cytotoxics and, ideally, small-molecule inhibitors, targeted degraders, or molecular glues.
- Solid understanding of ADC/DAC analytics, conjugate stability, and the PK/tox and developability implications of linker-payload design.
- Ability to operate independently and lead complex, cross-functional programs to concrete deliverables.
Preferred
- Experience conjugating small-molecule inhibitors, targeted degraders (e.g., PROTAC or molecular glue), beyond classical cytotoxics.
- Experience with multispecific antibodies and/or targeted protein degradation.
- Track record of generating linker/conjugation intellectual property (issued patents, invention disclosures).
- Prior experience establishing conjugation capabilities, platforms, or IP at a biotech.
- Experience supporting IND-enabling development and early clinical (Phase I) programs, particularly in oncology.
Compensation & Benefits
We offer a highly competitive compensation package, including equity participation that reflects the strategic importance of this role. The engagement begins as a contract with the potential for conversion to a permanent (full-time) position based on performance and business needs. As a permanent employee, PineTree offers comprehensive benefits, including medical and dental insurance, paid time off, and a 401(k) with a company match.
Physical Requirements
- Prolonged periods of sitting at a desk and working on a computer.
- Periods of standing and working in a laboratory environment may be required.
- Must be able to lift up to 20 pounds at times.
- An individual in this position may be exposed to laboratory and chemical hazards, including the
handling of cytotoxic and other potent compounds under appropriate safety controls.
Recruitment & Staffing Agencies: Pinetree does not accept unsolicited resumes from any source other than candidates. Any resume submitted by an agency in the absence of a signed agreement will automatically become the property of Pinetree, and Pinetree will not owe any referral or other fees with respect thereto.