Fulcrum Therapeutics, Inc. · NASDAQ:FULC
Fulcrum Therapeutics — Merger or Acquisition (August 2026)
26 slides from Fulcrum Therapeutics's merger presentation, Aug 17, 2026
Slide 1: Slate Medicines Corporate Overview
Exhibit 99.2 Slate Medicines Corporate Overview August 17, 2026
Slide 2: Disclaimers
Disclaimers This presentation (this “Presentation”) has been prepared by Slate Medicines, Inc. (the “Company” or “Slate”) for informational purposes only and shall not form the basis for or be relied on in connection with any investment decision with respect to the Company, Fulcrum Therapeutics, Inc
Slide 3: Fulcrum Therapeutics announces merger with Slate Medicines
Fulcrum Therapeutics announces merger with Slate Medicines • Stock-for-stock merger whereby all of Slate Medicine’s issued and outstanding capital stock will be exchanged for Fulcrum common stock • Concurrent $245 million private placement into Slate from a syndicate of leading healthcare investors
Slide 4: Slate Medicines is a biotech company advancing next-generation therapeutics for migraine
Slate Medicines is a biotech company advancing next- generation therapeutics for migraine The Science The Solution The Opportunity PACAP (pituitary adenylate cyclase- SLTE-1009 is a potentially Migraine is a prevalent, debilitating activating polypeptide) and VIP differentiated subcutaneous anti- ne
Slide 5: Slate Medicines is seeking to broaden the treatment paradigm for migraine
Slate Medicines is seeking to broaden the treatment paradigm for migraine Program Discovery Preclinical Phase 1 Phase 2 Phase 3 Milestones SLTE-1009* HREC approval received for P1 (Anti-PACAP/VIP mAb) initiation in AUS Potential best-in-class subcutaneous July 2026 anti-PACAP/VIP monoclonal antibody
Slide 6: Led by a team of experienced biopharma executives with a personal commitment to migraine
Led by a team of experienced biopharma executives with a personal commitment to migraine Executive Team Gregory Oakes, MBA Neil Buckley, MS Roger Cady, MD John Umstead, CPA Chief Executive Officer President and Chief Medical Officer Chief Financial Officer Chief Operating Officer Board Of Directors
Slide 7: Migraine patients are underserved by the existing standard of care
Migraine patients are underserved by the existing standard of care 7
Slide 8: Migraine is more than just a headache; it is one of the most prevalent, lifelong, and disabling neurological diseases
Migraine is more than just a headache; it is one of the most prevalent, lifelong, and disabling neurological diseases Migraine is the leading cause of disability in 1 people under the age of 50 Migraine is often a lifelong disease that affects people of all ages; Headache disorders are among the top
Slide 9: Existing preventative therapeutics, including CGRP antagonists, do not provide complete disease control
Existing preventative therapeutics, including CGRP antagonists, do not provide complete disease control for most patients • In pivotal studies in chronic migraine (CM) patients, only ~50% of patients experience a >50% reduction in monthly migraine or headache days, and only ~20% of patients experien
Slide 10: Despite modest efficacy, CGRP antagonists for prevention are a large and growing commercial market
Despite modest efficacy, CGRP antagonists for prevention are a large and growing commercial market Company Drug Modality Dosing frequency 2025 Sales $1,424M* Small molecule QOD (Pfizer 2025 annual report) $1,036M Small molecule QD (Abbvie 2025 8-K) ~$700M (est) Subcutaneous QM (Estimate from Q3 Zack
Slide 11: PACAP and VIP play a foundational role in migraine pathophysiology
PACAP and VIP play a foundational role in migraine pathophysiology 11
Slide 12: PACAP and VIP are neuropeptides that signal through multiple receptors
PACAP and VIP are neuropeptides that signal through multiple receptors and ligand blockade is required for efficacy PACAP exists in two isoforms: PACAP-38 and PACAP-27 • AMG301, a PAC1 receptor binding antibody, failed to bocunebart show a statistically significant benefit over VIP is a neuropeptide
Slide 13: Like CGRP, PACAP and VIP have each been shown to independently induce migraine-like headaches
Like CGRP, PACAP and VIP have each been shown to independently induce migraine-like headaches PACAP, VIP, and CGRP are all neuropeptides and have been shown to induce cephalic vasodilation and the induction of migraine-like headache in patients Neuropeptide Migraine induction rate Notes • 20-minute
Slide 14: Challenge studies have demonstrated that PACAP induces migraine independent of CGRP signaling
Challenge studies have demonstrated that PACAP induces migraine independent of CGRP signaling • Patients were randomized to receive either placebo or anti-CGRP monoclonal antibody eptinezumab (Vyepti) and then infused with PACAP-38 start at 120 minutes • There was no meaningful difference in physiol
Slide 15: PACAP-ligand binding is a clinically-validated approach to migraine prevention
PACAP-ligand binding is a clinically-validated approach to migraine prevention • In the Phase 2a HOPE study, bocunebart (Lu AG09222), an anti-PACAP IV ligand binding mAb, demonstrated a significant monthly migraine reduction in high frequency, treatment experienced chronic migraine o Patients in HOP
Slide 16: Bocunebart demonstrated complete reversal of PACAP-associated vasodilation, but only partial reversal of VIP effects
Bocunebart demonstrated complete reversal of PACAP-associated vasodilation, but only partial reversal of VIP associated effects In an infusion challenge study, bocunebart completely reversed PACAP-38 associated superficial temporal artery vasodilation, but only partially reverse the effects of VIP R
Slide 17: SLTE-1009: A potential best-in-class subcutaneous anti-PACAP/VIP monoclonal antibody for the prevention of migraine
SLTE-1009: A potential best-in-class subcutaneous anti- PACAP/VIP monoclonal antibody for the prevention of migraine 17
Slide 18: SLTE-1009: A potentially differentiated subcutaneous anti-PACAP/VIP monoclonal antibody
SLTE-1009: A potentially differentiated subcutaneous anti- PACAP/VIP monoclonal antibody for the prevention of migraine Bocunebart Property SLTE-1009 (Lu AG09222) Ligand Binding Yes Yes Yes PACAP-38 and PACAP-27 Yes VIP Yes Low affinity, partial affect Half-life extended Yes - YTE No Being developed
Slide 19: In functional cellular assays SLTE-1009 demonstrated equivalent potency to bocunebart on PACAP and enhanced blockade of VIP
In functional cellular assays SLTE-1009 demonstrated equivalent potency to bocunebart on PACAP and enhanced blockade of VIP Activity Antigen SLTE-1009 IC(50) Bocuenbart IC(50) PACAP38 0.23 nM 0.74 nM PAC1 neutralizing PACAP27 0.22 nM 0.29 nM PACAP38 PACAP27 PACAP38 0.53 nM 2.34 nM 3 2 7 2 4 A b s in
Slide 20: Activity in preclinical models of migraine
Activity in preclinical models of migraine • Umbellulone (UMB) is a UMB：12 mg Female C57BL/6J naturally occurring, 18-20 g, N = 8 allodynia-inducing -50 min Pain threshold Baseline test Priming by monoterpene ketone via Treatments (i.v.) test (1h) Randomization Restrain stress activation of Transien
Slide 21: SLTE-1009 thus far has demonstrated favorable preclinical data
SLTE-1009 thus far has demonstrated favorable preclinical data Formulation Product Profile Property Target SLTE-1009 Concentration ≥150 mg/mL Viscosity <15 cP Osmolality <500 mSOM/kg Potency Subvisible particles Stability Charge distribution Aggregation Autoinjector compatible volume Single ≤2 mL in
Slide 22: Demonstrated half-life extension in NHPs and ability to match Lundbeck IV PK via subcutaneous delivery
Demonstrated half-life extension in NHPs and ability to match Lundbeck IV PK via subcutaneous delivery Bocunebart 750 mg IV (P2a high-dose) vs. SLTE-1009 QM SC Modeling of expected human PK vs. bocunebart 750 (P2a) and 480 mg IV (P2b) shows possibility to Bocunebart 480 mg IV (P2b high-dose) vs. SLT
Slide 23: SLTE-1009 has the potential for up to quarterly subcutaneous administration
SLTE-1009 has the potential for up to quarterly subcutaneous administration Bocunebart 750 mg IV (P2a high-dose) vs. SLTE-1009 Q2M SC Bocunebart 480 mg IV (P2b high-dose) vs. SLTE-1009 Q3M SC Dose level and frequency expected to be evaluated in a Phase 2 dose- range finding study based on actual obs
Slide 24: Slate has a potential path to early value creation and program derisking with Phase 1 PK
Slate has a potential path to early value creation and program derisking with Phase 1 PK Additional Potential Catalysts pipeline Today: potential Initiating Phase 1 topline Phase 1 PK program Full P1 data differentiated anti- healthy volunteer and half-life data (safety and PK) details on PACAP/VIP
Slide 25: Building a world-class migraine-focused biotech with a pipeline of potentially best-in-class, differentiated assets
Building a world-class migraine-focused biotech with a pipeline of potentially best-in-class, differentiated assets • SLTE-2100 An anti-PACAP/VIP x CGRP bispecific antibody o Complete blockade of three neuropeptides implicated in migraine, PACAP, VIP, and CGRP for potential differentiated efficacy i
Slide 26: Slate Medicines is a biotech company focused on expanding treatment options for migraine patients
Slate Medicines is a biotech company focused on expanding treatment options for migraine patients The Solution SLTE-1009 is a potential best-in-class subcutaneous anti-PACAP monoclonal Lead asset SLTE- Experienced team Building a pipeline antibody for the prevention of migraine and 1009 is a potenti
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