Comprehensive Report on BHV-2100

I. Executive Summary

BHV-2100 is an orally administered, first-in-class, selective Transient Receptor Potential Melastatin 3 (TRPM3) antagonist currently under development by Biohaven Pharmaceuticals. The compound targets the TRPM3 ion channel, a novel mechanism implicated in neuroinflammatory pain signal transmission and the pathophysiology of migraine.[1] Preclinical investigations have demonstrated BHV-2100's capacity for potent pain reversal across various animal models, including models of neuropathic pain and chemotherapy-induced pain, as well as its ability to inhibit the release of Calcitonin Gene-Related Peptide (CGRP), a key mediator in migraine.[1]

Phase 1 clinical trials involving healthy volunteers have established that BHV-2100 is safe and well-tolerated. These studies also revealed favorable pharmacokinetic properties, characterized by rapid absorption and sustained plasma concentrations, which support its advancement into patient populations.[3] Notably, BHV-2100's pharmacological profile is distinguished by its peripheral restriction, aiming to minimize central nervous system (CNS) side effects, and it has not been associated with sedation or the thermoregulatory issues that have complicated the development of other TRP channel modulators.[4]

BHV-2100 is currently progressing through pivotal Phase 2 clinical development. A key study (NCT06603623) is evaluating its efficacy and safety in the acute treatment of migraine.[1] Concurrently, BHV-2100 is being investigated for neuropathic pain, with early clinical proof-of-concept data from a laser-evoked potential study anticipated in the first half of 2025.[8] The development of BHV-2100 for both acute migraine and chronic pain conditions highlights its potential to address significant unmet medical needs with a novel, non-opioid mechanism of action. Its "first-in-class" status signifies potential for high therapeutic reward, though this is balanced by the inherent risks of pioneering a new therapeutic target for which there are no established precedents in late-stage clinical efficacy for these indications.

II. Introduction to BHV-2100

A. Overview: Therapeutic Class and Novelty

BHV-2100 is an investigational small molecule drug, designed for oral administration.[2] It represents a novel therapeutic approach as a first-in-class, selective antagonist of the Transient Receptor Potential Melastatin 3 (TRPM3) ion channel.[1] This unique mechanism of action positions BHV-2100 as a non-opioid treatment candidate for pain and migraine, two conditions with substantial unmet medical needs.[3] A key characteristic of BHV-2100 is its peripheral restriction, a design feature intended to limit its activity to the peripheral nervous system, thereby minimizing potential central nervous system (CNS) side effects often associated with analgesics and migraine therapies.[4] This approach aims to offer effective pain and migraine relief without the sedative or cognitive side effects that can impair patients' daily functioning. The non-opioid nature of BHV-2100 is particularly significant in the context of the ongoing opioid crisis, highlighting its potential as a safer alternative for pain management if proven effective.[4]

B. Developer: Biohaven Pharmaceuticals

BHV-2100 is under development by Biohaven Pharmaceuticals (formerly Biohaven Research), a global clinical-stage biopharmaceutical company.[2] Biohaven is dedicated to the discovery, development, and commercialization of therapies for a range of neurological, neuropsychiatric, and rare diseases.[2] The company's research and development efforts span a diverse pipeline, which includes glutamate modulators, Kv7 ion channel modulators for epilepsy and mood disorders, and extracellular protein degraders for immunological diseases, among other innovative platforms.[6]

Biohaven has a notable history in the migraine field, having successfully developed and commercialized CGRP antagonists, such as Nurtec ODT (rimegepant) and zavegepant.[6] This prior success provides Biohaven with considerable experience and expertise in navigating the complexities of migraine drug development, including clinical trial design, regulatory interactions, and market introduction. Such institutional knowledge is invaluable for the advancement of BHV-2100, potentially streamlining its development path for migraine. Furthermore, Biohaven's diversified R&D strategy, reflected in its broad pipeline, allows the company to undertake ambitious projects like the development of a first-in-class molecule such as BHV-2100, while managing overall portfolio risk.

III. Mechanism of Action

A. Target: The Transient Receptor Potential Melastatin 3 (TRPM3) Ion Channel

The primary molecular target of BHV-2100 is the Transient Receptor Potential Melastatin 3 (TRPM3) ion channel.[2] TRPM3 is a calcium-permeable, nonselective cation channel. It is predominantly expressed in somatosensory neurons, which include nociceptors (pain-sensing neurons) located in critical sites for pain and migraine signaling such as the trigeminal ganglion and the dorsal root ganglia.[1] The expression in these key sensory ganglia directly implicates TRPM3 in the transmission pathways for pain and migraine, providing a strong biological basis for its antagonism as a therapeutic strategy. TRPM3 is recognized as a novel druggable target, and BHV-2100 is the first selective antagonist of this channel to advance into this stage of clinical development for these indications.[3] Compared to other TRP channels like TRPV1 and TRPA1, TRPM3 exhibits a broader expression pattern in peripheral neurons, which may contribute to its distinct physiological roles and therapeutic potential.[4] The novelty of targeting TRPM3 suggests that BHV-2100 could offer a new therapeutic option for patients who have not found adequate relief or who experience intolerable side effects with existing drug classes.

B. Role of TRPM3 in Pain Pathophysiology and Migraine

The TRPM3 ion channel is deeply involved in neuroinflammatory pain signal transmission.[1] Activation of TRPM3 by various stimuli, including noxious heat and certain chemical ligands (such as pregnenolone sulfate), leads to an influx of calcium ions into sensory neurons, which can evoke pain sensations.[4] Preclinical studies using TRPM3 antagonists or genetic deletion of the TRPM3 gene have consistently shown a reduction in pain transmission.[1] For instance, mice lacking TRPM3 do not develop pathological mechanical or thermal hypersensitivity in various pain models, underscoring the channel's critical role in these processes.[4]

Furthermore, TRPM3 expression and activity are functionally upregulated in animal models of inflammatory hyperalgesia and chemotherapy-induced neuropathic pain.[5] This suggests that the therapeutic impact of a TRPM3 antagonist like BHV-2100 might be more pronounced in pathological conditions where the target channel is overactive or its expression is increased.

Human genetic studies also support the role of TRPM3 in pain signaling and migraine. Specific gene variants in TRPM3 have been associated with an increased risk of developing migraine and with altered sensitivity to pain and heat in humans.[1] In the context of migraine, TRPM3 is co-expressed with other migraine-relevant genes within the human trigeminal ganglion.[1] A particularly significant finding is that selective activation of TRPM3 has been shown to induce the release of Calcitonin Gene-Related Peptide (CGRP) in rodent models.[1] CGRP is a well-validated neuropeptide in migraine pathophysiology, and therapies targeting CGRP or its receptor are established treatments. The ability of TRPM3 to modulate CGRP release provides a strong mechanistic link for the potential efficacy of BHV-2100 in migraine, suggesting it may act upstream to influence this critical pathway.

C. Pharmacological Effects of BHV-2100

BHV-2100 functions as a potent and selective antagonist of the TRPM3 ion channel. Its primary pharmacological effect is the inhibition of TRPM3 activity, which, based on preclinical evidence, leads to a reduction in pain signaling and the inhibition of CGRP release.[1] A defining feature of BHV-2100 is its peripherally restricted action, meaning its therapeutic effects are primarily mediated outside the central nervous system.[4] This characteristic is crucial for its anticipated safety profile. By limiting CNS penetration, BHV-2100 is expected to avoid centrally-mediated side effects such as sedation, cognitive impairment, or abuse liability, which are common concerns with many existing analgesics, particularly opioids.[4]

A significant advantage highlighted in both preclinical and early clinical development is the absence of thermoregulatory adverse events with BHV-2100.[4] Some other TRP channel modulators, notably TRPV1 antagonists, have faced development challenges due to on-target effects causing hyperthermia. BHV-2100's ability to circumvent this issue, likely due to its selectivity for TRPM3 and/or its peripheral restriction, represents a substantial step forward and de-risks a major potential hurdle. The potential to inhibit CGRP release offers a mechanistic rationale similar to that of successful anti-CGRP migraine therapies, but BHV-2100 provides an oral, small molecule alternative that acts at a novel upstream point in the pathway. This could translate to advantages in administration route, patient convenience, and potentially a different side effect profile or efficacy in patient populations who do not respond adequately to direct CGRP antagonism.

IV. Preclinical Development

A. In Vitro Studies: Potency (IC50​ values) and Selectivity Profile

The in vitro pharmacological profile of BHV-2100 has been characterized to determine its potency and selectivity for the TRPM3 channel. Studies using heterologous expression systems and sensory neurons demonstrated that BHV-2100 inhibits TRPM3-mediated calcium responses across species (human, mouse, and rat) with half-maximal inhibitory concentration (IC50​) values typically ranging between 1 and 10 nM.[5] More specifically, patch-clamp electrophysiology studies conducted on HEK293 cells expressing TRPM3 reported an IC50​ of 8.8 nM for the inhibition of TRPM3 neuronal activity.[5]

A critical aspect of BHV-2100's preclinical assessment is its selectivity. The compound exhibited greater than 1000-fold selectivity for TRPM3 when tested against a broad panel of other ion channels and receptors. This panel included other members of the TRP channel family, such as TRPA1, TRPV1, TRPM8, and TRPM7, for which IC50​ values were all greater than 10 µM. Similarly, BHV-2100 showed low affinity for key cardiovascular ion channels, including NaV​1.5, NaV​1.7, CaV​1.2, and hERG, with IC50​ values also exceeding 10 µM for these targets.[5] The high potency in the nanomolar range for TRPM3, coupled with this significant selectivity margin, indicates a favorable therapeutic window, suggesting that effective channel blockade can be achieved at concentrations unlikely to cause off-target effects. This high degree of selectivity, particularly the lack of significant activity on channels like TRPV1 (associated with thermoregulatory side effects) and critical cardiac ion channels, underpins the promising safety profile observed in subsequent studies.

Table 1: In Vitro Activity and Selectivity of BHV-2100

Target/Assay	Species	Assay Type	Result (IC50​)	Reference
TRPM3-mediated Ca2+ responses	Human, Mouse, Rat	Calcium influx	1-10 nM	5
TRPM3 neuronal activity (HEK293 cells)	Human	Patch clamp	8.8 nM	5
TRPA1	Not specified	Ion channel assay	>10 µM	5
TRPV1	Not specified	Ion channel assay	>10 µM	5
TRPM8	Not specified	Ion channel assay	>10 µM	5
TRPM7	Not specified	Ion channel assay	>10 µM	5
NaV​1.5 (cardiac sodium channel)	Not specified	Ion channel assay	>10 µM	5
NaV​1.7 (peripheral sodium channel)	Not specified	Ion channel assay	>10 µM	5
CaV​1.2 (L-type calcium channel)	Not specified	Ion channel assay	>10 µM	5
hERG (potassium channel)	Not specified	Ion channel assay	>10 µM	5

B. In Vivo Efficacy

1. Performance in Animal Models of Pain

BHV-2100 has demonstrated robust analgesic effects across a range of preclinical pain models, supporting its development for various pain conditions. When administered orally, BHV-2100 effectively inhibited pain induced by pregnenolone sulfate (PS), a known TRPM3 agonist, in both mice and rats, with median effective dose (ED50​) values of 1.3 mg/kg and 2.5 mg/kg, respectively.[5]

In models of neuropathic pain, such as those induced by nerve injury in rats, BHV-2100 produced a dose-dependent reduction in pain behaviors. Notably, these analgesic effects were observed without the significant sedation commonly associated with standard neuropathic pain treatments like pregabalin, when the latter was administered at a dose of 30 mg/kg.[5] This distinction is important, as sedation can be a major limiting side effect of current therapies, impacting patient quality of life and daily functioning.

Furthermore, BHV-2100 has shown efficacy in models of chemotherapy-induced neuropathic pain (CINP) and diabetic neuropathy. In CINP models, it reversed cold-induced pain, and in streptozotocin-induced diabetic neuropathy models, it significantly attenuated mechanical hypersensitivity in a dose-dependent manner.[5] The consistent efficacy across these diverse pain models—representing chemogenic, nerve injury-induced, chemotherapy-induced, and metabolic neuropathy—suggests that TRPM3 antagonism by BHV-2100 may target a fundamental mechanism common to various pain etiologies, thereby indicating broad potential clinical utility.

2. Evidence for Migraine Treatment

The rationale for developing BHV-2100 for migraine is supported by several lines of preclinical evidence. As previously mentioned, TRPM3 antagonists, including BHV-2100, have been shown to inhibit the release of CGRP in preclinical settings.[1] Given that CGRP is a well-established target in migraine, with multiple approved therapies effectively modulating its pathway, this finding provides a strong mechanistic link. BHV-2100 offers the potential to modulate this validated pathway via a novel upstream mechanism. Additionally, the co-expression of TRPM3 with other migraine-relevant genes in the human trigeminal ganglion, a key anatomical site in migraine pathophysiology, further strengthens this connection.[1] Human genetic studies also associate TRPM3 gene variants with an increased risk of migraine, reinforcing the channel's relevance to the human condition.[1]

C. Preclinical Safety: Key findings

Preclinical safety evaluations of BHV-2100 have revealed a favorable profile. The compound demonstrated high oral bioavailability in mice and rats, ranging from 55% to 85%, without inducing noticeable side effects at effective doses.[5] A critical safety finding is the absence of significant impact on body core temperature regulation or heart rate in rats, even at doses that produce analgesia. This is a significant distinction from some other TRP channel modulators, such as the TRPV1 antagonist AMG517, which was shown to cause hyperthermia in comparator preclinical studies.[4] The ability of BHV-2100 to avoid this on-target thermoregulatory effect, potentially due to its selectivity for TRPM3 or its predominantly peripheral action, is a major de-risking factor for its clinical development.

Tissue distribution studies have indicated that BHV-2100's activity is largely restricted to the peripheral nervous system.[4] This peripheral restriction is believed to reduce its susceptibility to CNS-mediated adverse events, such as sedation or abuse liability, which was supported by the lack of sedative effects observed in animal models compared to centrally acting drugs like pregabalin.[4] Furthermore, comprehensive IND (Investigational New Drug)-enabling toxicology studies have indicated wide safety margins for BHV-2100, supporting its progression into human clinical trials.[5]

V. Clinical Development Program

A. Phase 1 Studies (Healthy Volunteers - SAD/MAD)

1. Study Design and Objectives

The initial clinical evaluation of BHV-2100 involved randomized, placebo-controlled, sequential single ascending dose (SAD) and multiple ascending dose (MAD) studies in healthy adult volunteers aged 18–55 years.3

In the SAD portion, 39 participants were treated, with 30 receiving BHV-2100 and 9 receiving placebo. Single oral doses of BHV-2100 ranged from 25 mg, 75 mg, 150 mg, 250 mg, up to 500 mg, administered under fasting conditions. The 150 mg dose was also evaluated with a high-fat meal and in conjunction with famotidine to assess potential food effects and interactions with acid-reducing agents, respectively.3

In the MAD portion, 32 participants were treated. Subjects were randomized (3:1, BHV-2100 to placebo) to receive BHV-2100 at doses of 25 mg once daily (QD), 75 mg QD, 150 mg QD, or 150 mg twice daily (BID) for a duration of 14 days.3

The primary objectives for both SAD and MAD studies were to assess the safety, tolerability, and pharmacokinetic (PK) profile of BHV-2100.3

2. Pharmacokinetic Profile

The Phase 1 studies provided a comprehensive characterization of BHV-2100's pharmacokinetics in humans.

• Absorption and Tmax​: BHV-2100 demonstrated rapid absorption following oral administration. The time to reach maximum plasma concentration (Tmax​) was consistently observed to be approximately 1.5 to 2 hours across the single dose cohorts.[3]
• Half-life (T1/2​): The mean terminal elimination half-life (T1/2​) in the SAD studies ranged from approximately 8 to 12 hours.[3] In the MAD studies, at steady-state, the T1/2​ was similar, ranging from 8 to 10 hours.[4] This half-life supports the potential for once or twice daily dosing regimens.
• Dose Proportionality: The pharmacokinetic exposure to BHV-2100 increased in an approximately dose-proportional manner in the SAD cohorts, particularly at doses up to 150 mg.[3]
• Plasma Concentrations vs. EC50​/EC90​: Plasma concentrations of BHV-2100 rapidly exceeded the estimated 90% maximal effective concentration (EC90​), derived from preclinical models, typically within 20 minutes of administration, and were sustained above this threshold for several hours across all SAD dose levels tested.[3] Even at the lowest SAD dose of 25 mg, plasma concentrations reached EC90​ by 30 minutes. At the 150 mg SAD, plasma concentrations were approximately 4 times the EC90​ by 20 minutes and 7 times the EC90​ by Tmax​.[10]
• Multiple Dosing (MAD): With once-daily dosing in the MAD cohorts, minimal accumulation of BHV-2100 was observed.[4] A 75 mg QD regimen provided plasma concentrations greater than the estimated 50% maximal effective concentration (EC50​) over a 24-hour period. A 150 mg BID regimen resulted in plasma concentrations exceeding EC90​ over a 24-hour period.[3] Specific data on time above EC50​ and EC90​ were reported for various MAD regimens, indicating sustained target engagement.[4]
• Food and Famotidine Effects: The administration of a 150 mg dose of BHV-2100 with a high-fat meal resulted in a delayed Tmax​; however, plasma concentrations still surpassed the EC90​ threshold by 20 minutes post-dose. Co-administration with famotidine, an acid-reducing agent, did not significantly alter the exposure to BHV-2100 at the 150 mg dose level.[3] These findings suggest that BHV-2100 dosing is unlikely to be significantly affected by food intake or common acid-reducing medications, offering potential for convenient administration.

The rapid attainment of predicted therapeutic concentrations is particularly advantageous for an acute migraine treatment, where swift onset of relief is highly desired by patients.

Table 2: Summary of BHV-2100 Phase 1 Key Pharmacokinetic Parameters

Parameter	Value/Observation	Dosing Condition(s)	Reference(s)
Tmax​ (Time to Peak Plasma Concentration)	Approx. 1.5–2 hours	SAD (fasting)	3
T1/2​ (Terminal Elimination Half-life)	Approx. 8–12 hours (SAD) <br> Approx. 8-10 hours (MAD, steady state)	SAD, MAD	3
Dose Proportionality	Approximately dose-proportional (SAD, up to 150 mg)	SAD (fasting)	3
Plasma Conc. vs. EC90​ (SAD)	Exceeded EC90​ after 20 mins (all doses) <br> 25mg: reached EC90​ by 30 mins <br> 150mg: 4×EC90​ by 20 mins, 7×EC90​ by Tmax​	SAD (fasting)	3
Plasma Conc. vs. EC50​/EC90​ (MAD)	75mg QD: >EC50​ over 24h <br> 150mg BID: >EC90​ over 24h	MAD	3
Effect of Food (150mg SAD, high-fat meal)	Delayed Tmax​, but conc. >EC90​ by 20 mins	SAD with food	3
Effect of Famotidine (150mg SAD)	No significant impact on exposure	SAD with famotidine	3
Accumulation (MAD)	Minimal with QD dosing	MAD	4

3. Safety and Tolerability

BHV-2100 demonstrated an excellent safety and tolerability profile throughout the Phase 1 SAD and MAD studies, across all dose levels tested, including single doses up to 500 mg and multiple doses up to 150 mg BID for 14 days.1

No dose-limiting toxicities (DLTs) were identified.4 There were no serious adverse events (SAEs) or severe treatment-emergent adverse events (TEAEs) reported during these studies.3 The majority of AEs observed were mild in intensity and resolved spontaneously without requiring medical intervention.3 Importantly, no AEs led to discontinuation of the study drug.4

In the SAD cohorts, when pooling data across all BHV-2100 doses, the only AEs reported in more than one participant were dizziness and fatigue, each occurring in 2 out of 30 (6.7%) BHV-2100-treated participants, compared to 0 out of 9 placebo-treated participants.[3] In the MAD cohorts, no specific TEAE occurred in more than one participant receiving BHV-2100. Notably, in the highest MAD cohort (150 mg BID), no TEAEs were reported.[3]

Consistent with preclinical predictions, there were no clinically significant trends observed in vital signs, including body temperature, nor in laboratory values or electrocardiogram (ECG) parameters.[3] Specifically, BHV-2100 did not cause thermoregulatory AEs (such as hyperthermia or hypothermia) or sedation in human subjects.[4] This clean safety profile in early human studies, particularly the absence of side effects that have hampered other TRP channel modulators or are common with standard pain and migraine therapies, strongly supports the continued clinical development of BHV-2100.

Table 3: Summary of Adverse Events in BHV-2100 Phase 1 Studies

Study/Dose Group	N (BHV-2100 / Placebo)	Most Common AEs (>1 participant in BHV-2100 group)	Incidence (BHV-2100 vs. Placebo)	Severe AEs	SAEs	DLTs	Discontinuations due to AEs	Reference(s)
SAD (Pooled BHV-2100 doses)	30 / 9	Dizziness <br> Fatigue	6.7% vs. 0% <br> 6.7% vs. 0%	None	None	None	None	3
MAD (All BHV-2100 doses)	24 / 8 (approx.)	No TEAE in >1 participant	N/A	None	None	None	None	3
MAD (150mg BID)	(Specific N not detailed but part of MAD)	No TEAEs reported	N/A	None	None	None	None	3

Note: Specific N for MAD placebo group derived from 3:1 randomization for 32 total MAD participants.

B. Phase 2 Program: Migraine

1. Pivotal Trial NCT06603623 (Acute Treatment of Migraine)

a. Rationale and Design

Biohaven has initiated a pivotal Phase 2 clinical trial (NCT06603623) to evaluate BHV-2100 for the acute treatment of migraine.[1] The rationale for this trial is strongly supported by preclinical data implicating TRPM3 in pain signaling and CGRP release, coupled with human genetic evidence linking TRPM3 to migraine risk.[1] The study is a randomized, double-blind, placebo-controlled trial, a gold-standard design for assessing efficacy and safety. This trial is explicitly designed to support registration, indicating that positive results could form a significant basis for regulatory approval submissions.[3]

b. Patient Population and Dosing Regimens

The trial is enrolling adult patients who experience 2 to 8 moderate to severe migraine attacks per month and have fewer than 15 headache days per month, characteristic of episodic migraine.[1] Participants are randomized in a 1:1:1 ratio to receive a single oral dose of either BHV-2100 75 mg, BHV-2100 150 mg, or placebo. This dose is to be taken at the onset of a single migraine attack of moderate to severe pain intensity.[1] An earlier presentation from AHS 2024 also mentioned a potential 25 mg dose being considered for Phase 2 migraine studies, though the current pivotal trial focuses on 75 mg and 150 mg.[10] The selection of 75 mg and 150 mg doses is well-grounded in the Phase 1 pharmacokinetic data, which showed that 75 mg QD provided plasma concentrations above EC50​ for 24 hours, and 150 mg BID provided concentrations above EC90​ for 24 hours, indicating sustained target engagement at these dose levels.[3]

c. Endpoints

The trial employs co-primary endpoints that are accepted by the FDA for migraine registration studies: pain freedom at 2 hours post-dose and freedom from the patient-identified most bothersome symptom (MBS) at 2 hours post-dose.1 These endpoints reflect clinically meaningful outcomes for patients experiencing an acute migraine attack.

Additional assessments will evaluate pain relief at 2 hours, return to normal function at 2 hours, and freedom from common migraine-associated symptoms such as photophobia (light sensitivity), phonophobia (sound sensitivity), and nausea at 2 hours. The durability of effect will also be assessed through measures of sustained pain freedom and sustained pain relief at 24 and 48 hours post-dose. Pharmacokinetic parameters (drug plasma concentrations) and comprehensive safety and tolerability data will also be collected.1

d. Current Status, Enrollment, and Timelines

The pivotal Phase 2 study NCT06603623 was initiated in September 2024.[3] It is actively enrolling, with a target of approximately 575 participants across roughly 60 clinical sites in the United States.[1] Biohaven anticipates reporting topline data from this proof-of-concept migraine study in the first half of 2025.[8] The designation of this Phase 2 trial as "pivotal" suggests that Biohaven is positioning it to potentially serve as a key efficacy study for future regulatory submissions, should the results be strongly positive.

Table 4: Overview of Phase 2 Migraine Trial (NCT06603623) Design and Endpoints

Feature	Detail	Reference(s)
Trial ID	NCT06603623	1
Phase	Pivotal Phase 2	1
Design	Randomized, double-blind, placebo-controlled	1
Patient Population	Adults with 2–8 moderate/severe migraine attacks/month, <15 headache days/month	1
Interventions	Single oral dose: BHV-2100 75mg, BHV-2100 150mg, or Placebo (1:1:1 randomization)	1
Co-Primary Endpoints	1. Pain freedom at 2 hours post-dose <br> 2. Most bothersome symptom (MBS) freedom at 2 hours post-dose	1
Key Secondary Endpoints	Pain relief at 2h; normal function at 2h; freedom from photophobia, phonophobia, nausea at 2h; sustained pain freedom/relief at 24h & 48h; PK; safety/tolerability	1
Enrollment Target	Approx. 575 participants	1
Number of Sites	Approx. 60 US sites	1
Status (as of late 2024)	Initiated September 2024; Ongoing, Enrolling	1
Expected Topline Data	1H 2025	8

C. Phase 2 Program: Pain

1. Neuropathic Pain Studies

a. Laser-Evoked Potential/Hyperalgesia Study

To gain early insights into BHV-2100's efficacy in pain, Biohaven is conducting an innovative study using a laser-evoked potential (LEP) / laser-induced hyperalgesia model in healthy volunteers.[7] This experimental pain model allows for objective measurement of pain responses and the effects of analgesic compounds. Preliminary data from this study, highlighted by Biohaven, indicated that BHV-2100 reduced laser heat-induced pain and associated brain evoked potentials.[12] These findings are considered the first clinical proof-of-concept for the TRPM3 inhibitor class in a pain-relevant paradigm and recapitulate the strong preclinical efficacy observed across various pain models.[12] Topline data from this laser-evoked potential study are anticipated in the first half of 2025.[7] Positive outcomes from this objective pain model would provide further validation for advancing BHV-2100 into patient populations with clinical pain conditions.

b. EudraCT 2024-512187-57

In addition to US-based studies, BHV-2100 is also being evaluated in a clinical trial for pain in Europe, registered under the EudraCT number 2024-512187-57.[3] While detailed design specifics for this particular European trial are not extensively available in the provided information beyond its focus on pain, its existence signifies a global development strategy for BHV-2100 in pain indications. Conducting trials in multiple major regulatory regions like the US and Europe can facilitate broader data generation and support future marketing applications in these key markets.

2. Other Investigated Pain Indications

The preclinical efficacy of BHV-2100 in diverse animal models of pain has provided a strong rationale for its investigation in several specific neuropathic pain conditions.[5] Based on these preclinical findings and company disclosures, BHV-2100 is being considered or is under investigation for general neuropathic pain, chemotherapy-induced neuropathy (CINP), diabetic neuropathy, and pain following nerve injury.[2] According to GlobalData, BHV-2100 is currently in Phase II development for Neuropathic Pain (Neuralgia).[2] These conditions often present significant treatment challenges and are associated with a high unmet medical need, particularly for effective and well-tolerated non-opioid therapies. The development in these areas aligns with BHV-2100's profile as a peripherally restricted, non-sedating analgesic.

VI. Intellectual Property

A. Overview of Key Patents and Applications

Biohaven Pharmaceuticals, along with its collaborators, has been actively securing intellectual property rights for its TRPM3 antagonist program, including compounds related to BHV-2100. Several patent applications and potentially granted patents aim to protect the novel chemical entities and their therapeutic uses.

One key piece of intellectual property is U.S. Patent Application US-20240173290-A1, titled "Inhibitors of TRPM3 and their uses." This application lists Kumar J, et al. as inventors and was published on May 30, 2024. Notably, this specific patent application is cited in Biohaven's IASP 2024 scientific poster discussing the preclinical and Phase 1 data for BHV-2100, directly linking this intellectual property to the BHV-2100 program.4

International patent application WO2022152715A1, titled "Inhibitors of trpm3 and their uses," with Katholieke Universiteit Leuven listed as an applicant, also covers TRPM3 inhibitors for the treatment or prevention of migraine and other pain conditions.[15] While Biohaven is not the primary applicant on this specific WO application, their collaborative relationship with Katholieke Universiteit Leuven is evident in other filings.

For example, Australian patent application AU2023274389A1, titled "New derivatives for treating trpm3 mediated disorders," lists both Katholieke Universiteit Leuven and Biohaven Therapeutics Ltd. as applicants. This application, filed on May 25, 2023, describes compounds of a general formula (I) as TRPM3 antagonists and claims their use for treating TRPM3-mediated disorders, including pain, epilepsy, and inflammatory hypersensitivity.[16]

This pattern of patent filings indicates a strategic effort to protect the novel chemical matter related to TRPM3 antagonism and its application in various therapeutic areas. Such patent protection is crucial for securing market exclusivity and supporting the substantial investment required for pharmaceutical research and development. The collaboration with academic institutions like Katholieke Universiteit Leuven is a common and effective strategy in pharmaceutical innovation, often bridging early-stage discovery from academia with the development and commercialization expertise of a biopharmaceutical company.

VII. Regulatory Status

A. Current Designations (e.g., Fast Track, Orphan Drug)

Based on the available information, BHV-2100 has not yet received Fast Track designation or Orphan Drug designation from the U.S. Food and Drug Administration (FDA) or equivalent designations from the European Medicines Agency (EMA) for its current lead indications of migraine and neuropathic pain.[9] While Biohaven has successfully obtained such designations for other drug candidates in its pipeline, such as troriluzole for spinocerebellar ataxia [7], these do not automatically extend to BHV-2100.

Migraine is a prevalent condition and thus would not typically qualify for Orphan Drug designation, which is reserved for rare diseases or conditions. Fast Track designation is granted to drugs that treat serious conditions and fill an unmet medical need. While migraine and many forms of neuropathic pain are serious and have unmet needs, the specific criteria for Fast Track would need to be met and an application submitted by Biohaven. It is possible that such designations could be sought at later stages of development if specific patient populations or aspects of the drug's profile strongly align with the regulatory criteria for these expedited programs.

B. Regional Development

BHV-2100 is undergoing clinical development in major pharmaceutical markets, indicating a global development strategy.

In the United States, the pivotal Phase 2 trial for the acute treatment of migraine (NCT06603623) is actively enrolling participants across approximately 60 sites.1 Additionally, the laser-evoked potential study for pain is also being conducted in the US.

In Europe, a clinical trial for pain is registered under the EudraCT number 2024-512187-57.3

Conducting clinical trials in both the US and Europe concurrently allows Biohaven to gather data from diverse patient populations and is a common strategy to support simultaneous or sequential regulatory submissions to both the FDA and EMA, aiming for broader market access upon successful completion of the development program.

VIII. Discussion and Future Outlook

A. Summary of Key Findings and Strengths of BHV-2100

BHV-2100 has emerged as a promising first-in-class, orally administered, peripherally restricted TRPM3 antagonist. Its novel mechanism of action, targeting a channel implicated in both pain and migraine pathophysiology, offers a distinct therapeutic approach.1 Preclinical studies have robustly demonstrated its potency in various pain models and provided a strong mechanistic rationale for its use in migraine, including the inhibition of CGRP release.1

The Phase 1 clinical program in healthy volunteers has been a significant success, establishing an excellent safety and tolerability profile for BHV-2100. Crucially, it did not elicit CNS side effects like sedation or the thermoregulatory issues (e.g., hyperthermia) that have plagued other TRP channel modulators.3 The pharmacokinetic profile is favorable, characterized by rapid absorption leading to potentially quick onset of action, and a half-life supporting manageable dosing regimens. Plasma concentrations achieved in Phase 1 studies were sustained above levels predicted to be efficacious based on preclinical models.3

B. Potential Therapeutic Impact and Unmet Needs Addressed

Should BHV-2100 prove successful in later-stage trials, its therapeutic impact could be substantial. Migraine and various forms of neuropathic pain affect millions of individuals worldwide, and many patients continue to experience inadequate relief or intolerable side effects with current treatment options.[1] BHV-2100's potential to offer effective relief via a novel, non-opioid mechanism is a key attribute. Its non-sedating profile and lack of thermoregulatory concerns further enhance its potential to become a well-tolerated option, improving patient compliance and quality of life.[3] For migraine, it could provide a new oral acute treatment option, potentially for those who do not respond to or cannot take existing therapies like triptans or CGRP-targeted drugs. For pain, particularly neuropathic pain, a novel non-opioid with a favorable side effect profile would be a major advancement.

C. Anticipated Milestones and Future Development Trajectory

The first half of 2025 is a critical period for BHV-2100, with topline data expected from two key studies: the laser-evoked potential study in pain and the pivotal Phase 2 proof-of-concept trial in acute migraine (NCT06603623).7 The preliminary positive signals from the laser-evoked potential study, suggesting clinical proof-of-concept for the TRPM3 inhibitor class in pain, are encouraging.12

Positive outcomes from these studies will be instrumental in guiding the late-stage development strategy for BHV-2100. If the Phase 2 migraine trial meets its endpoints with a favorable safety profile, Biohaven may proceed towards Phase 3 development and discussions with regulatory authorities regarding a registration pathway. Similarly, strong data from the pain studies could lead to dedicated Phase 2b or Phase 3 trials in specific neuropathic pain indications, such as chemotherapy-induced neuropathy or diabetic neuropathy, where preclinical rationale is strong.

D. Potential Challenges and Considerations

Despite the promising early data, BHV-2100 faces challenges inherent in drug development. As a first-in-class agent targeting a novel mechanism, the translation of efficacy from early studies and experimental models to larger, more heterogeneous patient populations in Phase 2 and Phase 3 trials remains a hurdle. Establishing long-term safety with chronic exposure, particularly if developed for chronic pain conditions, will also be essential.

The therapeutic landscapes for both migraine and pain are dynamic and competitive. In migraine, several classes of acute and preventive treatments are available, including well-established CGRP-targeted therapies. In pain, while the need for non-opioids is high, demonstrating superior efficacy and/or safety over existing analgesics will be important for market differentiation.

The successful navigation of these clinical and regulatory challenges, contingent on robust efficacy and safety data from ongoing and future trials, will ultimately determine the future role of BHV-2100 in clinical practice. The upcoming data readouts in 1H 2025 will be pivotal in shaping this trajectory.

IX. References

1 Neurology.org. (2025, April 7). BHV-2100, a First-in-Class TRPM3 Antagonist in Development for the Treatment of Migraine (P7-12.009).

2 Pharmaceutical-technology.com. (2024, April 12). BHV-2100 by Biohaven for Migraine: Likelihood of Approval.

3 Neurology.org. (2025, April 7). Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-class TRPM3 Antagonist for Pain and Migraine (S11.004).

4 Biohaven.com. (2024). Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-Class TRPM3 Antagonist for Pain.

8 Biospace.com. (2025). Biohaven Reports Recent Business Developments and Fourth Quarter and Full Year 2024 Financial Results.

7 Biospace.com. (2024). Biohaven Reports Third Quarter 2024 Financial Results and Recent Business Developments.

2 Pharmaceutical-technology.com. (2024, April 12). BHV-2100 by Biohaven for Migraine: Likelihood of Approval. 2

6 Prnewswire.com. (2024, September 30). Biohaven Initiates Pivotal Trial of Novel Investigational Drug for Treatment of Migraine.

3 Neurology.org. (2025, April 7). Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-class TRPM3 Antagonist for Pain and Migraine (S11.004). 3

1 Neurology.org. (2025, April 7). BHV-2100, a First-in-Class TRPM3 Antagonist in Development for the Treatment of Migraine (P7-12.009). 1

9 Ir.biohaven.com. (2025, March 3). Biohaven Reports Recent Business Developments and Fourth Quarter and Full Year 2024 Financial Results.

13 Globaldata.com. (2025, January 23). Likelihood of Approval and Phase Transition Success Rate Model - BHV-2100 in Neuropathic Pain (Neuralgia).

14 Pharmaceutical-technology.com. (2024, December 31). BHV-2100 by Biohaven for Neuropathic Pain (Neuralgia): Likelihood of Approval.

5 Biohaven.com. (2024). BHV-2100, a First-in-Class TRPM3 Antagonist for the Treatment of Pain and Migraine.

17 Youtube.com. (2025, May 6). First-in-human trial of BHV-2100 for the treatment of pain.

3 Neurology.org. (2025, April 7). Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-class TRPM3 Antagonist for Pain and Migraine (S11.004). 3

5 Biohaven.com. (2024). BHV-2100, a First-in-Class TRPM3 Antagonist for the Treatment of Pain and Migraine. 5

14 Pharmaceutical-technology.com. (2024, December 31). BHV-2100 by Biohaven for Neuropathic Pain (Neuralgia): Likelihood of Approval. 14

18 Biohaven.com. TRPM3 Antagonist for Neuropathic Pain.

19 Synapse.patsnap.com. BHV-2100 - Drug Targets, Indications, Patents.

4 Biohaven.com. (2024). Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-Class TRPM3 Antagonist for Pain. 4

12 Ir.biohaven.com. (2025, January 13). Biohaven Highlights Portfolio Progress, Innovation, and Anticipated Milestones at the 43rd Annual J.P. Morgan Healthcare Conference.

11 Prnewswire.com. (2025, March 3). Biohaven Reports Recent Business Developments and Fourth Quarter and Full Year 2024 Financial Results.

9 Ir.biohaven.com. (2025, March 3). Biohaven Reports Recent Business Developments and Fourth Quarter and Full Year 2024 Financial Results. 9

13 Globaldata.com. (2025, January 23). Likelihood of Approval and Phase Transition Success Rate Model - BHV-2100 in Neuropathic Pain (Neuralgia). 13

10 Biohaven.com. (2024). First-in-Human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of the First-in-Class TRPM3 Antagonist BHV-2100.

6 Prnewswire.com. (2024, September 30). Biohaven Initiates Pivotal Trial of Novel Investigational Drug for Treatment of Migraine. 6

5 Biohaven.com. (2024). BHV-2100, a First-in-Class TRPM3 Antagonist for the Treatment of Pain and Migraine. 5

18 Biohaven.com. TRPM3 Antagonist for Neuropathic Pain. 18

14 Pharmaceutical-technology.com. (2024, December 31). BHV-2100 by Biohaven for Neuropathic Pain (Neuralgia): Likelihood of Approval. 14

13 Globaldata.com. (2025, January 23). Likelihood of Approval and Phase Transition Success Rate Model - BHV-2100 in Neuropathic Pain (Neuralgia). 13

1 Neurology.org. (2025, April 7). BHV-2100, a First-in-Class TRPM3 Antagonist in Development for the Treatment of Migraine (P7-12.009). 1

20 Researchgate.net. (2025, April). Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-class TRPM3 Antagonist for Pain and Migraine (S11.004). (Abstract, full text not provided)

4 Biohaven.com. (2024). Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-Class TRPM3 Antagonist for Pain. 4

15 Patents.google.com. WO2022152715A1 - Inhibitors of trpm3 and their uses.

18 Biohaven.com. TRPM3 Antagonist for Neuropathic Pain. 18

16 Patents.google.com. AU2023274389A1 - New derivatives for treating trpm3 mediated disorders.

3 Neurology.org. (2025, April 7). Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-class TRPM3 Antagonist for Pain and Migraine (S11.004). 3

10 Biohaven.com. (2024). First-in-Human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of the First-in-Class TRPM3 Antagonist BHV-2100. 10

14 Pharmaceutical-technology.com. (2024, December 31). BHV-2100 by Biohaven for Neuropathic Pain (Neuralgia): Likelihood of Approval. 14

13 Globaldata.com. (2025, January 23). Likelihood of Approval and Phase Transition Success Rate Model - BHV-2100 in Neuropathic Pain (Neuralgia). 13

12 Ir.biohaven.com. (2025, January 13). Biohaven Highlights Portfolio Progress, Innovation, and Anticipated Milestones at the 43rd Annual J.P. Morgan Healthcare Conference. 12

21 Delta.larvol.com. BHV-2100 / University of Leuven, Biohaven. (Limited data, date references)

11 Prnewswire.com. (2025, March 3). Biohaven Reports Recent Business Developments and Fourth Quarter and Full Year 2024 Financial Results. 11

8 Biospace.com. (2025). Biohaven Reports Recent Business Developments and Fourth Quarter and Full Year 2024 Financial Results. 8

3 Neurology.org. (2025, April 7). Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-class TRPM3 Antagonist for Pain and Migraine (S11.004). 3

10 Biohaven.com. (2024). First-in-Human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of the First-in-Class TRPM3 Antagonist BHV-2100. 10

12 Ir.biohaven.com. (2025, January 13). Biohaven Highlights Portfolio Progress, Innovation, and Anticipated Milestones at the 43rd Annual J.P. Morgan Healthcare Conference. 12

9 Ir.biohaven.com. (2025, March 3). Biohaven Reports Recent Business Developments and Fourth Quarter and Full Year 2024 Financial Results. 9

22 Researchgate.net. (2025, April). BHV-2100, a First-in-Class TRPM3 Antagonist in Development for the Treatment of Migraine (P7-12.009). (Abstract, full text not provided)

5 Biohaven.com. (2024). BHV-2100, a First-in-Class TRPM3 Antagonist for the Treatment of Pain and Migraine. 5

3 Pharmaceutical-technology.com. (2024, April 12). BHV-2100 by Biohaven for Migraine: Likelihood of Approval. 2

3 Neurology.org. (2025, April 7). Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-class TRPM3 Antagonist for Pain and Migraine (S11.004). 3

3 Neurology.org. (2025, April 7). BHV-2100, a First-in-Class TRPM3 Antagonist in Development for the Treatment of Migraine (P7-12.009). 1

3 Prnewswire.com. (2024, September 30). Biohaven Initiates Pivotal Trial of Novel Investigational Drug for Treatment of Migraine. 6

3 Prnewswire.com. (2024, September 30). Biohaven Initiates Pivotal Trial of Novel Investigational Drug for Treatment of Migraine. 6

3 Neurology.org. (2025, April 7). Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-class TRPM3 Antagonist for Pain and Migraine (S11.004). 3

3 Ir.biohaven.com. (2025, March 3). Biohaven Reports Recent Business Developments and Fourth Quarter and Full Year 2024 Financial Results. 9

3 Pharmaceutical-technology.com. (2024, December 31). BHV-2100 by Biohaven for Neuropathic Pain (Neuralgia): Likelihood of Approval. 14

3 Youtube.com. (2025, May 6). First-in-human trial of BHV-2100 for the treatment of pain. 17

1 Neurology.org. (2025, April 7). BHV-2100, a First-in-Class TRPM3 Antagonist in Development for the Treatment of Migraine (P7-12.009). 1

4 Biohaven.com. (2024). Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-Class TRPM3 Antagonist for Pain. 4

5 Neurology.org. (2025, April 7). Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-class TRPM3 Antagonist for Pain and Migraine (S11.004). 3

5 Biohaven.com. (2024). BHV-2100, a First-in-Class TRPM3 Antagonist for the Treatment of Pain and Migraine. 5

5 Pharmaceutical-technology.com. (2024, December 31). BHV-2100 by Biohaven for Neuropathic Pain (Neuralgia): Likelihood of Approval. 14

5 Biohaven.com. (2024). Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-Class TRPM3 Antagonist for Pain. 4

5 Ir.biohaven.com. (2025, January 13). Biohaven Highlights Portfolio Progress, Innovation, and Anticipated Milestones at the 43rd Annual J.P. Morgan Healthcare Conference. 12

5 Prnewswire.com. (2025, March 3). Biohaven Reports Recent Business Developments and Fourth Quarter and Full Year 2024 Financial Results. 11

23 (Inaccessible - relates to US20240173290A1)

15 Patents.google.com. WO2022152715A1 - Inhibitors of trpm3 and their uses. 15

16 Patents.google.com. AU2023274389A1 - New derivatives for treating trpm3 mediated disorders. 16

Works cited

1. BHV-2100, a First-in-Class TRPM3 Antagonist in Development for the Treatment of Migraine (P7-12.009) - Neurology.org, accessed May 24, 2025, https://www.neurology.org/doi/10.1212/WNL.0000000000211319
2. BHV-2100 by Biohaven for Migraine: Likelihood of Approval - Pharmaceutical Technology, accessed May 24, 2025, https://www.pharmaceutical-technology.com/data-insights/bhv-2100-biohaven-migraine-likelihood-of-approval/
3. Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-class TRPM3 Antagonist for Pain and Migraine (S11.004) - Neurology.org, accessed May 24, 2025, https://www.neurology.org/doi/10.1212/WNL.0000000000211307
4. Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-Class TRPM3 Antagonist for Pain - Biohaven, accessed May 24, 2025, https://www.biohaven.com/wp-content/uploads/IASP-2024-Poster-BHV-2100-Phase-1-SAD-MAD.pdf
5. BHV-2100, a First-in-Class TRPM3 Antagonist for the Treatment of Pain and Migraine - Biohaven, accessed May 24, 2025, https://www.biohaven.com/wp-content/uploads/IASP-2024-Poster-BHV-2100-Preclinical.pdf
6. Biohaven Initiates Pivotal Trial of Novel Investigational Drug for Treatment of Migraine, accessed May 24, 2025, https://www.prnewswire.com/news-releases/biohaven-initiates-pivotal-trial-of-novel-investigational-drug-for-treatment-of-migraine-302261939.html
7. Biohaven Reports Third Quarter 2024 Financial Results and Recent Business Developments - BioSpace, accessed May 24, 2025, https://www.biospace.com/press-releases/biohaven-reports-third-quarter-2024-financial-results-and-recent-business-developments
8. Biohaven Reports Recent Business Developments and Fourth Quarter and Full Year 2024 Financial Results - BioSpace, accessed May 24, 2025, https://www.biospace.com/press-releases/biohaven-reports-recent-business-developments-and-fourth-quarter-and-full-year-2024-financial-results
9. Biohaven Reports Recent Business Developments and Fourth Quarter and Full Year 2024 Financial Results, accessed May 24, 2025, https://ir.biohaven.com/news-releases/news-release-details/biohaven-reports-recent-business-developments-and-fourth-quarter/
10. First-in-Human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of the First-in-Class TRPM3 Antagonist BHV-2100 i - Biohaven, accessed May 24, 2025, https://www.biohaven.com/wp-content/uploads/AHS-2024-Oral-Presentation-BHV-2100-Phase-1-SAD-MAD.pdf
11. Biohaven Reports Recent Business Developments and Fourth Quarter and Full Year 2024 Financial Results - PR Newswire, accessed May 24, 2025, https://www.prnewswire.com/news-releases/biohaven-reports-recent-business-developments-and-fourth-quarter-and-full-year-2024-financial-results-302389517.html
12. Biohaven Highlights Portfolio Progress, Innovation, and Anticipated Milestones at the 43rd Annual J.P. Morgan Healthcare Conference; Reports Positive Degrader Data with Rapid, Deep, and Selective Lowering of Galactose-Deficient IgA1 with Next Generation Potential Therapy for IgA Nephropathy, accessed May 24, 2025, https://ir.biohaven.com/news-releases/news-release-details/biohaven-highlights-portfolio-progress-innovation-and/
13. Likelihood of Approval and Phase Transition Success Rate Model - BHV-2100 in Neuropathic Pain (Neuralgia) - GlobalData, accessed May 24, 2025, https://www.globaldata.com/store/report/bhv-2100-in-neuropathic-pain-neuralgia-loa-innovation-and-trend-analysis/
14. BHV-2100 by Biohaven for Neuropathic Pain (Neuralgia): Likelihood of Approval, accessed May 24, 2025, https://www.pharmaceutical-technology.com/data-insights/bhv-2100-biohaven-neuropathic-pain-neuralgia-likelihood-of-approval/
15. WO2022152715A1 - Inhibitors of trpm3 and their uses - Google ..., accessed May 24, 2025, https://patents.google.com/patent/WO2022152715A1/en
16. AU2023274389A1 - New derivatives for treating trpm3 mediated ..., accessed May 24, 2025, https://patents.google.com/patent/AU2023274389A1/en
17. First-in-human trial of BHV-2100 for the treatment of pain - YouTube, accessed May 24, 2025, https://www.youtube.com/watch?v=mwdDaHCEWow
18. TRPM3 Antagonist for Neuropathic Pain - Biohaven, accessed May 24, 2025, https://www.biohaven.com/pipeline/innovation-engine/trpm3/
19. BHV-2100 - Drug Targets, Indications, Patents - Patsnap Synapse, accessed May 24, 2025, https://synapse.patsnap.com/drug/3ca8e04e41f2478ca00be1a3d77230b2
20. Safety, Tolerability, and Pharmacokinetics of BHV-2100, a First-in-class TRPM3 Antagonist for Pain and Migraine (S11.004) | Request PDF - ResearchGate, accessed May 24, 2025, https://www.researchgate.net/publication/390587638_Safety_Tolerability_and_Pharmacokinetics_of_BHV-2100_a_First-in-class_TRPM3_Antagonist_for_Pain_and_Migraine_S11004
21. BHV-2100 / University of Leuven, Biohaven - LARVOL DELTA, accessed May 24, 2025, https://delta.larvol.com/Products/?ProductId=f5da83f3-9fe0-4e50-a2fb-b3de2748c320
22. BHV-2100, a First-in-Class TRPM3 Antagonist in Development for the Treatment of Migraine (P7-12.009) | Request PDF - ResearchGate, accessed May 24, 2025, https://www.researchgate.net/publication/390587816_BHV-2100_a_First-in-Class_TRPM3_Antagonist_in_Development_for_the_Treatment_of_Migraine_P7-12009
23. accessed January 1, 1970, https://patents.google.com/patent/US20240173290A1/en