Randi Isaacs

About Randi Isaacs

Randi Isaacs, M.D. (age 69) is Chief Medical Officer of Werewolf Therapeutics (ticker: HOWL), a role she has held since November 2020. She holds a B.A. in Chemistry from Wellesley College and an M.D. with honors from Dartmouth Medical School, and completed residency/postdoctoral training at UCSF and University of Pennsylvania with fellowship at Memorial Sloan-Kettering Cancer Center . As CMO, she leads clinical strategy across the company’s conditionally activated cytokine and TCE programs; under her leadership, WTX‑124 established a recommended dose of 18 mg (mono and combo) with expansion arms (melanoma, RCC, cSCC, and PD‑L1+ NSCLC) and plans for an FDA meeting to map the registrational path, including an initial monotherapy strategy in advanced melanoma . The program reported a complete response in second‑line cSCC sustained for over a year off drug and translation of key IL‑2 design principles (safety/therapeutic index, PK) into the clinic .

Past Roles

External Roles

Fixed Compensation

• Notes (all other comp): includes life insurance premiums ($918), LTD insurance tax gross‑up ($1,589), and 401(k) company match ($10,350 in 2024) .
• Annual bonuses are based on Company corporate goals and individual performance as determined by the Board/Comp Committee in their discretion; no metric weights disclosed .

Performance Compensation

Annual Cash Incentive

• The Company does not disclose detailed financial/operational metric weights for executive bonuses; Committee retains discretion .

Equity Awards (Grants)

• Policy: Post‑IPO option grants have exercise price equal to the closing market price on grant date; Company has granted time‑ and performance‑based options historically but no RSUs to executive officers to date .

Outstanding Options (as of Dec 31, 2024)

• Vesting terms for options: multi‑year equal monthly vesting from the vesting start date (footnote schedules aligned to each grant year) .

Equity Ownership & Alignment

Employment Terms

• Status: At‑will employment; employment agreement effective April 29, 2021 .
• Current role: Chief Medical Officer since November 2020 .
• Target bonus: Employment agreement initially set target at 40% of base salary; 2024 target confirmed at 40% .
• Severance (outside change‑in‑control): If terminated without cause or resigns for good reason, 9 months of base salary paid over regular payroll plus Company‑paid COBRA premiums for the same period; 6 months’ additional vesting acceleration on time‑based equity .
• Change‑in‑control (double trigger): If such termination occurs within 12 months following a change‑in‑control, 12 months of base salary paid in a lump sum, target bonus for the year paid lump sum, Company‑paid COBRA premiums for 12 months, and full vesting acceleration of time‑based equity .
• Restrictive covenants: Standard agreements covering non‑competition, non‑solicitation, confidentiality, and assignment of inventions .
• Clawback: Nasdaq‑compliant policy covering incentive‑based compensation (financial metrics, stock price, TSR) for the three completed fiscal years preceding a restatement .

Performance & Track Record

• Clinical execution: Translation of WTX‑124’s design into the clinic with differentiated safety (no vascular leak syndrome) and strong therapeutic index; RDE set at 18 mg (mono/combo) with expansion arms across melanoma, RCC, cSCC (added after a profound early response) and PD‑L1+ NSCLC .
• Regulatory strategy: Planning FDA meeting to define the path forward, initially prioritizing a single‑arm monotherapy expansion in advanced metastatic melanoma (2nd/3rd line) with discussion of registrational options thereafter .
• Platform breadth: Experience spans IL‑2 (WTX‑124) and IL‑12 (WTX‑330) conditional activation; early outpatient dosing of IL‑12 with biomarker activity and a confirmed PR in melanoma supports broader applicability .
• Capital discipline and prioritization: Clear resource allocation toward lead clinical asset while advancing TCE portfolio with potential business development optionality .

Investment Implications

• Alignment vs performance: Isaacs’ pay mix is equity‑heavy via time‑vested stock options and discretionary annual cash bonuses without disclosed metric weights—supporting retention and long‑term alignment but offering limited direct pay‑for‑performance linkage (no PSUs; no RSUs to executives to date) .
• Retention and cadence: The 200,000‑share 2024 option grant vests monthly through Jan 1, 2028 (and the 2023 grant through Jan 1, 2027), creating ongoing retention hooks and a steady vesting cadence that may periodically enable liquidity under open trading windows or Rule 10b5‑1 plans .
• Change‑in‑control economics: Double‑trigger acceleration (12 months’ salary and target bonus; full vesting on time‑based equity) strikes a balance between retention and shareholder alignment, and avoids single‑trigger acceleration .
• Ownership and selling pressure: Beneficial ownership equals 1.3% of shares outstanding (via options exercisable within 60 days), signaling meaningful exposure; anti‑hedging/pledging policy reduces misalignment risk and discourages levered selling pressure .
• Governance and red flags: Presence of modest tax gross‑ups for LTD insurance in “All Other Compensation” is a minor negative but not economically significant; adoption of a robust clawback policy is a positive shareholder protection .

Sources: Werewolf Therapeutics 2025 DEF 14A (executive bios, compensation, ownership, policies) and company transcripts featuring Dr. Isaacs’ remarks on pipeline strategy and clinical progress .