Parabilis Medicines, Inc. · NASDAQ:PBLS
Parabilis Medicines — Investor Presentation (September 2026)
32 slides from Parabilis Medicines's investor presentation, September 2026
Slide 1: Creating Extraordinary Medicines
September 2026 Creating Extraordinary Medicines Drugging Previously Undruggable Intracellular Drivers of Serious Diseases
Slide 2: Forward-looking statements & disclaimer
Forward-looking statements & disclaimer This presentation contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. The words "anticipate," "believe," "continue," "could," "estimate,"
Slide 3: From platform breakthrough to advancing unique Helicon medicines
Parabilis: From platform breakthrough to advancing unique Helicon medicines 2026 & Beyond: Building the next chapter 2024: Platform Zolucatetide advancing 2018: First successful de 2023: Mathai Mammen expansion into targeted toward Ph3 registrational novo hit discovery screen joins as CEO, President
Slide 4: Led by an experienced leadership team and Board
Led by an experienced leadership team and Board LEADERSHIP TEAM • Visionary company builder and drug developer with BOARD OF DIRECTORS decades of experience in pharma and biotech Mathai Mammen, M.D., Ph.D. Mathai Mammen, CEO, President & Chairman, Parabilis • Spearheaded discovery and development of
Slide 5: Uniquely positioned to deliver near-term catalysts and long-term impact
Uniquely positioned to deliver near-term catalysts and long-term impact Advancing zolucatetide toward Phase 3 registrational study in desmoid tumors (1H 2027) with value-creating catalysts in 2026-2027 and beyond Targeting a multi-billion-dollar opportunity that also spans FAP, ACP, and other Wnt/β-
Slide 6: Our pipeline of differentiated Helicon therapeutic candidates
Our pipeline of differentiated Helicon therapeutic candidates IND- ANTICIPATED UPCOMING PROGRAMS INDICATIONS DISCOVERY PHASE 1 PHASE 2 PHASE 3 ENABLING MILESTONES • Maturing Phase 1/2 data Q4 2026 Desmoid Tumors • Phase 3 initiation 1H 2027 Familial Adenomatous • FAP cohort initiation 2H 2026 Zoluca
Slide 7: Helicons: Redefining what is druggable inside a cell
Helicons: Redefining what is druggable inside a cell Antibody-like control of disease-driving intracellular targets The Challenge: Undruggable Biology Our Solution: Helicons • Estimated 80% of biologically validated disease Stabilized α-helical peptides combine the precision of antibodies with targe
Slide 8: Zolucatetide: The first and only β-catenin:TCF inhibitor
Zolucatetide: The first and only β-catenin:TCF inhibitor Target previously undruggable for decades present in over 10% of tumors across a range of tumor types Zolucatetide acts downstream of Pursuing a Pipeline-in-a-Product Strategy for Zolucatetide β-catenin or APC mutations INDICATIONS MUTATIONS E
Slide 9: Desmoid Tumors: Locally invasive tumors with chronic, life-altering burden
Desmoid Tumors: Locally invasive tumors with chronic, life-altering burden Therapy with improved efficacy, tolerability and time to response could significantly expand market opportunity Sizable, chronic patient Substantial symptomatic High medical need population and functional burden despite exist
Slide 10: Zolucatetide in Desmoid: Data supports advancing to registrational study
Zolucatetide in Desmoid: Data supports advancing to registrational study 25 Response-Evaluable* Patients (All data as of Feb 16, 2026) • 100% DCR: Stable disease or better across all patients and all dose levels • 74% ORR including one CR: 14 out of 19 patients with ≥2 post-baseline scans responded
Slide 11: Zolucatetide in Desmoid: Data supports advancing to registrational study
Zolucatetide in Desmoid: Data supports advancing to registrational study 38 patients dosed across dose escalation and dose optimization cohorts (All data as of Feb 16, 2026) • All patients remain on study except one patient who achieved a CR and discontinued treatment due to relocation away from stu
Slide 12: Zolucatetide in Desmoid: Volumetric data reinforces speed of response and dose dependence
Zolucatetide in Desmoid: Volumetric data reinforces speed of response and dose dependence RECIST 1.1 per Investigator Volumetric per Central Reader • Deep responses observed across dose levels in both volumetric scans and RECIST 1.1 900 mg 900 mg 450 mg 450 mg 150 mg 150 mg 900 mg 450 mg 150 mg • Ra
Slide 13: Zolucatetide in Desmoid: Well-tolerated safety profile
Zolucatetide in Desmoid: Well-tolerated safety profile Safety and tolerability as of Feb 16, 2026 data cut-off: • Tolerability matters greatly for desmoid patients who are otherwise active and healthy • Skin, gastrointestinal (GI), and ovarian/reproductive toxicities are common issues seen with curr
Slide 14: Zolucatetide in Desmoid: Well-tolerated safety profile
Zolucatetide in Desmoid: Well-tolerated safety profile Treatment-related Adverse Events (TRAEs) in Part 1 in ≥ 15% Patients (As of Feb 16, 2026) *Includes blood bilirubin increased; ** Includes blood sodium decreased; ^Grade 3 hyperbilirubinemia based on data error - corrected to Grade 2 after data
Slide 15: Phase 3 trial designed for label superiority and market differentiation
Zolucatetide in Desmoid: Phase 3 trial designed for label superiority and market differentiation Proposed Key Endpoints Study Population Zolucatetide Dual Primary: Randomize 1:1 • PFS (RECIST 1.1) or ORR Treatment-naïve, Secondary: recurrent, or refractory • Duration of response patients with desmoi
Slide 16: Familial Adenomatous Polyposis (FAP): 100% driven by APC mutations
Familial Adenomatous Polyposis (FAP): 100% driven by APC mutations, causing polyp growth and inevitable progression to CRC if not removed • Shared β-catenin biology and overlapping patient populations with desmoid o Approximately 10% of patients with desmoid tumor have FAP o Approximately 3% of FAP
Slide 17: FAP: Patients face a lifetime of disease burden and fear with no approved drug therapy
FAP: Patients face a lifetime of disease burden and fear with no approved drug therapy AGE 10-15 AGE 15-25 AGE 25+ Childhood and teens: Late teens/young adults: Rest of adult life: Active surveillance Major GI surgery Lifelong management § >34K patient prevalence in US1 § Colectomy is often performe
Slide 18: Zolucatetide in FAP: Potential to reduce pre-cancerous polyp burden
Zolucatetide in FAP: Potential to reduce pre-cancerous polyp burden • Desmoid patient with FAP enrolled in ongoing Phase 1/2 study of zolucatetide Case Study #1 • APC mutation with history of FAP and large abdominal desmoid tumor, post colectomy Strong clinical response in desmoid tumor Promising re
Slide 19: Zolucatetide in FAP: Potential to reduce pre-cancerous polyp burden
Zolucatetide in FAP: Potential to reduce pre-cancerous polyp burden • Desmoid patient with FAP enrolled in ongoing Phase 1/2 study of zolucatetide Case Study #2 • APC mutation with history of FAP and large abdominal desmoid tumor, post colectomy Imaging of the 3rd portion of the duodenum Recent trea
Slide 20: Adamantinomatous Craniopharyngioma (ACP): A debilitating, chronic disease with no approved systemic therapy
Adamantinomatous Craniopharyngioma (ACP): A debilitating, chronic disease with significant morbidity and no approved systemic therapy A lifelong disease driven by Lifelong multi-systemic No approved a single acquired mutation complications systemic therapy § Conservative estimate of 5K-9K § Vision l
Slide 21: Zolucatetide in ACP: Tumor reductions observed in patients with ACP
Zolucatetide in ACP: Tumor reductions observed in 3 patients with ACP Baseline Week 8 Patient 1: Partial response of -56% at week 16 (confirmed PR) Baseline Week 24 Patient 2: Has maintained stable disease for over 48 weeks, with a best tumor reduction of -19.2%; patient remains on study since initi
Slide 22: Zolucatetide in HCC: Single-patient clinical activity consistent with expected β-catenin biology
Zolucatetide in HCC: Single-patient clinical activity consistent with expected β-catenin biology • Heavily pre-treated HCC patient with history of cirrhosis β-catenin activating mutations Case study • 4 pathogenic mutations (incl. β-catenin), 4 prior lines of therapy seen in ~30% of HCC patients • P
Slide 23: Zolucatetide in Rare Tumors: Responses in multiple Wnt/β-catenin-driven tumor types
Zolucatetide in Rare Tumors: Responses in multiple Wnt/β-catenin-driven tumor types highlights opportunity for a tumor-agnostic development pathway 20 RECIST 1.1 responses, including one complete response (as of Feb 16, 2026) • 39 efficacy evaluable patients with tumors of low genomic complexity • R
Slide 24: Building a lasting β-catenin franchise with a relentless focus on patient impact
Building a lasting β-catenin franchise with a relentless focus on patient impact Advance β-catenin degraders as Expand into additional indications next-gen therapeutics where the beyond desmoid tumors, FAP, and approach may help further ACP into other Wnt/β-catenin-driven enhance efficacy, tolerabil
Slide 25: ERG Degrader: Potential first-in-class ERG degrader targeting a historically undruggable cancer driver
ERG Degrader: Potential first-in-class ERG degrader targeting a long- recognized, yet historically undruggable, cancer driver TMPRSS2 ERG Why is ERG a critical target to drug? 1 2 3 14 1 2 3 4 11 • TMPRSS2:ERG is the most prevalent genomic alteration in TMPRSS2:ERG prostate cancer, present in 40-50%
Slide 26: ERG Degrader: Dose-dependent, single-agent anti-tumor activity in ERG-fusion models
ERG Degrader: Dose-dependent, single-agent anti-tumor activity in ERG- fusion models; synergy in combination with enzalutamide Preclinical anti-tumor activity seen in ERG+ xenograft models Single agent and combination Single agent anti-tumor activity in VCaP CDX model anti-tumor activity in an enzal
Slide 27: Allosteric ARON Degrader: Differentiated target with potential to overcome resistance
Allosteric ARON Degrader: Differentiated target with the potential to combine with standard of care and overcome resistance Why target the “ON” form of AR allosterically? • All current approved AR-targeting therapies bind to the AROFF AF-2 Bound Helicon (in AR LBD domain) conformation Testosterone i
Slide 28: Allosteric ARON Degrader: Early signals of single-agent activity and additivity
Allosteric ARON Degrader: Early signals of single-agent activity and additivity in combination with enzalutamide Preclinical data from in vivo and in vitro AR amplified VCaP models Single agent anti-tumor activity in VCaP CDX model Combination additivity with enzalutamide in vitro Pattabiraman DR, e
Slide 29: Helicon Platform: Fully integrated and AI-enabled
Helicon Platform: Fully integrated and AI-enabled Repeatable, scalable, and hard to replicate ü Enabled by a decade of high-volume proprietary data generation ü AI models trained on proprietary in-house data, proprietary industry leading complex peptide synthesis ü Extensive platform IP and accumula
Slide 30: One integrated synthesis platform reaches broad chemical space and learns each cycle
One integrated synthesis platform reaches broad chemical space, synthesizes compounds faster, and learns more each cycle Differentiated Building Blocks Automated Peptide Synthesis at a A DMTA Cycle Reach a Broader Design Space Scale Rare Outside Pharma Measured in Weeks 1,300+ 12 automated peptide s
Slide 31: Regeneron Collaboration: Expanding our Helicon platform into new therapeutic areas
Regeneron Collaboration: Expanding our Helicon platform into new therapeutic areas and modalities with strong deal economics • Unlocks a novel class of Helicon therapeutics targeting historically undruggable and challenging intracellular targets via antibody-Helicon conjugates (AHCs), enabling expan
Slide 32: Strong balance sheet supports our path to key value-creating milestones
Strong balance sheet supports our path to key value-creating milestones Anticipated Key Upcoming Milestones $1.1 billion in cash, cash equivalents, and Zolucatetide marketable securities as of June 30, 2026 Desmoid tumors • Maturing Ph1/2 data in Q4 2026 • FDA alignment on Ph3 design in Q4 2026 • Ph
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