Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

Yes
The device description explicitly mentions "proprietary software informed by structural and functional MRI and designed to identify the individualized target within the L-DLPFC for stimulation," which strongly suggests the use of AI/ML for image analysis and target identification. The name "SAINT Technology" (Stanford Accelerated Intelligent Neuromodulation Therapy) also includes the word "Intelligent," further supporting the presence of AI/ML.

Therapeutic

Yes
The device is indicated for the treatment of Major Depressive Disorder (MDD), which is a medical condition, making it a therapeutic device.

Diagnostic

No

The device is indicated for the treatment of Major Depressive Disorder (MDD), not for diagnosis. It is a non-invasive repetitive transcranial magnetic stimulation (rTMS) system designed to deliver magnetic pulses for therapeutic purposes.

SaMD (Software as a Medical Device)

No

The device description explicitly states that the system "consists of hardware devices (stimulator with treatment coil and neuronavigation system)" in addition to proprietary software.

IVD (In Vitro Diagnostic)

Based on the provided information, this device is not an IVD (In Vitro Diagnostic).

Here's why:

IVD Definition: In Vitro Diagnostics are medical devices used to perform tests on samples taken from the human body, such as blood, urine, or tissue, to detect diseases, conditions, or infections.
Device Function: The Magnus Neuromodulation System with SAINT Technology is a non-invasive repetitive transcranial magnetic stimulation (rTMS) system. It delivers magnetic pulses to the brain to treat Major Depressive Disorder. It does not analyze samples taken from the body.
Intended Use: The intended use is for the treatment of MDD, not for the diagnosis of MDD or any other condition through the analysis of biological samples.

The device uses imaging (MRI) to guide the treatment, but the treatment itself is a physical intervention, not an in vitro diagnostic test.

PCCP (Predetermined Change Control Plan) Authorized

No
The provided text does not contain any explicit statement that the FDA has reviewed and approved or cleared a Predetermined Change Control Plan (PCCP) for this specific device.

Overview

Intended Use / Indications for Use

The Magnus Neuromodulation System with SAINT Technology is indicated for the treatment of Major Depressive Disorder (MDD) in adult patients who have failed to achieve satisfactory improvement from prior antidepressant medication in the current episode.

Product codes

OBP, GWF, HAW

Device Description

The Magnus Neuromodulation System (MNS) with SAINT Technology is a non-invasive repetitive transcranial magnetic stimulation (rTMS) system that delivers individualized and navigationally directed repetitive magnetic pulses to the left dorsolateral prefrontal cortex (L-DLPFC) to treat Major Depressive Disorder (MDD) in adult patients who have failed to achieve satisfactory improvement from prior antidepressant medication in the current episode. The MNS with SAINT Technology is available for prescription use only and is intended for use by trained medical professionals in either an inpatient or outpatient setting. The Magnus Neuromodulation System consists of hardware devices (stimulator with treatment coil and neuronavigation system) intended to deliver SAINT Technology; that is, rTMS (as intermittent theta burst stimulation (iTBS)) to a target area within the L-DLPFC along with proprietary software informed by structural and functional MRI and designed to identify the individualized target within the L-DLPFC for stimulation. Also included in the system are a coil and monitor for motor threshold determination, which is used to inform patient-specific stimulation settings. SAINT Technology is the combination of using the specific individualized target for treatment along with a proprietary accelerated treatment protocol that condenses treatment to five days. The Magnus Neuromodulation System is designed to support successful delivery of SAINT Technology.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

structural and functional MRI

Anatomical Site

left dorsolateral prefrontal cortex (L-DLPFC)

Indicated Patient Age Range

adult patients

Intended User / Care Setting

trained medical professionals in either an inpatient or outpatient setting.

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Clinical testing was performed to provide assurance of safety and effectiveness of the Magnus Neuromodulation System with SAINT Technology. The system was evaluated in four clinical studies, three open-label and one randomized and sham controlled.

Title of Study: High-dose Spaced theta-burst TMS as a Rapid-acting Antidepressant in Highly Refractory Depression
Number of Participants: 6
Summary of Results: 5/6 (83.3%) responded (≥50% decrease in Hamilton Depression Rating Scale (HDRS-17) and 4/6 remitted (HDRS

Regulation Number and Section

§ 882.5805 Repetitive transcranial magnetic stimulation system.

(a)
Identification. A repetitive transcranial magnetic stimulation system is an external device that delivers transcranial repetitive pulsed magnetic fields of sufficient magnitude to induce neural action potentials in the prefrontal cortex to treat the symptoms of major depressive disorder without inducing seizure in patients who have failed at least one antidepressant medication and are currently not on any antidepressant therapy.(b)
Classification. Class II (special controls). The special control is FDA's “Class II Special Controls Guidance Document: Repetitive Transcranial Magnetic Stimulation System.” See § 882.1(e) for the availability of this guidance document.

Summary

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Image /page/0/Picture/0 description: The image contains two logos. On the left is the Department of Health & Human Services logo. On the right is the FDA logo, which includes the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

September 1, 2022

Magnus Medical, Inc. Susan Noriega VP Regulatory Affairs 1350 Old Bayshore Highway, Suite 600 Burlingame, CA 94010

Re: K220177

Trade/Device Name: Magnus Neuromodulation System (MNS) with SAINT Technology, Model Number 1001K Regulation Number: 21 CFR 882.5805 Regulation Name: Repetitive Transcranial Magnetic Stimulation System Regulatory Class: Class II Product Code: OBP Dated: August 2, 2022 Received: August 2, 2022

Dear Susan Noriega:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's

1

requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

for Pamela Scott Assistant Director DHT5B: Division of Neuromodulation and Physical Medicine Devices OHT5: Office of Neurological and Physical Medicine Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) [not yet assigned] K220177

Device Name

Magnus Neuromodulation System (MNS) with SAINT® Technology

Indications for Use (Describe)

The Magnus Neuromodulation System with SAINT Technology is indicated for the treatment of Maior Depressive Disorder (MDD) in adult patients who have failed to achieve satisfactory improvement from prior antidenressant medication in the current episode.

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpa

| Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary Provided in Accordance with 21 CFR §807.92(c)

magnusmedical

Date Summary Prepared:	August 30, 2022
510(k) Number:	K220177
510(k) Owner:	Magnus Medical, Inc.
1350 Old Bayshore Highway, Suite 600
Burlingame CA 94010 USA
(415) 690-7358
Submitter and Official Contact:	Susan Noriega
Magnus Medical, Inc.
1350 Old Bayshore Highway, Suite 600
Burlingame CA 94010 USA
susan@magnusmed.com
(650) 793-1966
Trade Name:	Magnus Neuromodulation System (MNS) with SAINT
Technology
Common Name:	Transcranial Magnetic Stimulation Device
Classification Name:	Repetitive Transcranial Magnetic Stimulator for Treatment
of Major Depressive Disorder
Primary Classification Regulation:	21 CFR §882.5805
Primary Product Code:	OBP
Secondary Classification and Code:	21 CFR §882.1870/GWF
21 CFR §882.4560/HAW
Substantially Equivalent Device:	Nexstim Navigated Brain Therapy (NBT) System 2
Nexstim Plc
Helsinki, Finland
Premarket Notification K182700
Cleared on March 22, 2019
Device Description:	The Magnus Neuromodulation System (MNS) with SAINT
Technology is a non-invasive repetitive transcranial
magnetic stimulation (rTMS) system that delivers
individualized and navigationally directed repetitive
magnetic pulses to the left dorsolateral prefrontal cortex (L-

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DLPFC) to treat Major Depressive Disorder (MDD) in adult patients who have failed to achieve satisfactory improvement from prior antidepressant medication in the current episode.

The MNS with SAINT Technology is available for prescription use only and is intended for use by trained medical professionals in either an inpatient or outpatient setting.

The Magnus Neuromodulation System consists of hardware devices (stimulator with treatment coil and neuronavigation system) intended to deliver SAINT Technology; that is, rTMS (as intermittent theta burst stimulation (iTBS)) to a target area within the L-DLPFC along with proprietary software informed by structural and functional MRI and designed to identify the individualized target within the L-DLPFC for stimulation. Also included in the system are a coil and monitor for motor threshold determination, which is used to inform patient-specific stimulation settings. SAINT Technology is the combination of using the specific individualized target for treatment along with a proprietary accelerated treatment protocol that condenses treatment to five days. The Magnus Neuromodulation System is designed to support successful delivery of SAINT Technology.

The Magnus Neuromodulation System with SAINT Intended Use: Technology is intended for the delivery of SAINT neuromodulation therapy to treat major depressive disorder (MDD) in adult patients who have failed to achieve satisfactory improvement from prior antidepressant medication in the current episode.

Technology Comparison:

The Magnus Neuromodulation System with SAINT Technology has the same intended use and technological characteristics as the predicate device.

Compatible Hardware: The Magnus Neuromodulation System is a complete set of mutually compatible hardware components that have been specifically selected and evaluated to safely and effectively deliver SAINT Technology in conjunction with the Magnus Cloud Software. The following includes the set of hardware components included with the Magnus Neuromodulation System:

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Item	Qty	Magnus Part #	Supplier Name/Model	Supplier Part #	510(k) Clearance
Stimulator	1	1002	MagVenture/X100	9016E0711	K173620
Treatment Coil	1	1003	MagVenture/Cool-B65	9016E0491	K171967
Motor Threshold Coil	1	1004	MagVenture/C-B60	9016E0673	K171967
Coil Arm	1	1005	MagVenture/Super Flexible
Arm	9016B0181	K173620
Stimulator Cart	1	1006	MagVenture/Trolley with
Holding Arrangements	9016B0383	K173620
Isolation Transformer	1	1007	MagVenture/Isolation
Transformer	9016D0031	K173620
Cooling System	1	1008	MagVenture/Coil Cooler Unit	9016B0151	K173620
Evoked Response
Monitor	1	1009	MagVenture/MEP Monitor	9016C0711	K162873
Neuronavigation
System with
accessories (cart and
PC)	1	1010	Brain Science Tools
(Soterix)/Neural Navigator	HD-SWN
(nav)
HD-SWTA
(cart)
HD-SWAPC
(pc)	K191422

MagVenture devices and accessories are supplied by Tonica Elektronik / MagVenture Brain Science Tools Neural Navigator is supplied by Soterix Medical

All hardware components were utilized in non-clinical bench performance testing as included in their respective 510(k) clearances. Stimulator, Treatment Coil, Motor Threshold Coil, Coil Arm, Stimulator Cart, Isolation Transformer, Cooling System, and Evoked Response Monitor hardware components were additionally utilized in clinical performance testing.

Table 1: Technology Comparison for the Magnus Neuromodulation System vs. the Predicate
Device
	Predicate Device	Proposed Device	Notes
Characteristic	Nexstim NBT System 2
K182700	Magnus Neuromodulation
System with SAINT
Technology
Intended Use	The Nexstim Navigated
Brain Therapy (NBT)
System 2 is intended for the
treatment of major
depressive disorder in adult
patients who have failed to
achieve satisfactory
improvement from prior	The Magnus
Neuromodulation System
(MNS) with SAINT
Technology is intended for
the delivery of SAINT
neuromodulation therapy to
treat major depressive
disorder (MDD) in adult	No difference
	Predicate Device	Proposed Device	Notes
	antidepressant medication in
the current episode.	patients who have failed to
achieve satisfactory
improvement from prior
antidepressant medication in
the current episode.
Main System
Hardware	• TMS Stimulator
• Motor Threshold and
Treatment Coil
• Tracking System for coil
positioning
• Evoked response monitor
for motor threshold
determination
• Cooling Unit	• TMS Stimulator
• Treatment Coil
• Tracking System for coil
positioning
• Evoked response monitor
for motor threshold
determination
• Cooling Unit
• Motor Threshold Coil	The predicate device
combines motor threshold
measurement and stimulation
treatment in one coil while
the Magnus System utilizes
two separate dedicated
purpose coils.
Treatment Target
Identification	Proprietary software utilizing
structural MRI to assist in
locating the target area
within the L-DLPFC for
depression therapy.	Proprietary software utilizing
structural and functional
MRI data to locate the target
area within the L-DLPFC for
depression therapy.	The Magnus System uses
functional MRI connectivity
data in addition to structural
MRI data to inform the
individual treatment target
localization software. Both
Magnus and predicate
methods aid in localization
of appropriate target areas
within the L-DLPFC for
stimulation and both
methods provide more
individual specificity than
the historically used external
anatomical landmarks.
Treatment Coil
Positioning	Real time visualization of the
treatment target relative to
the treatment coil position
via a tracking system
(neuronavigation system)	Real time visualization of the
treatment target relative to
the treatment coil position
via a tracking system
(neuronavigation system)	No difference
Motor Threshold
Determination	Visual inspection of finger
movement + EMG	Visual inspection of finger
movement + EMG	No difference
Treatment Intensity
Determination	Motor threshold and
electrical field model is used
to adjust stimulation
intensity	Motor threshold and depth-
correction is used to adjust
stimulation intensity	Nexstim and Magnus both
primarily rely on MT to
determine treatment
intensity. Nexstim also uses
a proprietary electrical field
model to orient the rotation
of the coil, while Magnus
uses a depth correction to
adjust for differences in
distance between motor
cortex and frontal cortex at
the target.
Stimulation
Protocol	10 Hz and iTBS	iTBS	The Magnus
Neuromodulation System
with SAINT Technology
uses only iTBS; the 10 Hz
protocol is not needed for the
Magnus System
	Predicate Device	Proposed Device	Notes
Area of Brain
Stimulated	L-DLPFC	L-DLPFC	No difference

6

7

Treatment Protocol Comparison: The Magnus Neuromodulation System with SAINT Technology utilizes the same type of treatment (intermittent theta burst stimulation/iTBS) as the predicate device but with more pulses (90,000 vs. 18,000) delivered over a shorter period of time (five days vs. six weeks) thus allowing for a more rapid response and more flexibility in terms of where treatment can be delivered; the more compressed schedule makes acute inpatient treatment more feasible.

Table 2: Treatment Protocol Comparison of SAINT Technology iTBS vs. Predicate iTBS

Treatment
Parameter	Nexstim NBT System 2
K182700
(predicate device)	Magnus
Neuromodulation
System with SAINT
Technology (proposed
device)	Notes
Stimulation
Dose	600 pulses per
session/day, 12,000-
18,000 pulses total	1,800 pulses per
session, 18,000 pulses
per day, 90,000 pulses
total	The number of pulses and timing of
sessions are optimized for effectiveness
and compressed treatment schedule with
no impact on safety.
Magnetic Field
Intensity	120% Motor Threshold	90% Motor Threshold	iTBS administered at amplitudes less than
100% of motor threshold may be safer
and more focal, and may be more
effective than iTBS at amplitudes greater
than 100% motor threshold.
Pulse
Frequency	50 Hz	50 Hz	No difference
Pulses per
burst	3	3	No difference
Burst
Frequency	5 Hz	5 Hz	No difference
Stimulus Train
Duration	2 seconds	2 seconds	No difference
Inter-train
Interval	8 seconds	8 seconds	No difference
Magnetic
Pulses per
Session	600	1800
Treatment
Session
Duration	3.3 minutes	10 minutes	The number of pulses and timing of
sessions are optimized for effectiveness
Treatment
Sessions per
Day	1	10	and compressed treatment schedule with
no impact on safety.
Treatment
Sessions per
Week	5	50

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| Treatment
Parameter | Nexstim NBT System 2
K182700
(predicate device) | Magnus
Neuromodulation
System with SAINT
Technology (proposed
device) | Notes |
|--------------------------------|-------------------------------------------------------|-----------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------|
| Total
Treatment
Minutes | 99 | 500 | |
| Total
Treatment
Sessions | 30 | 50 | |
| Total
Treatment
Pulses | 18,000 | 90,000 | |
| Treatment
Duration | 6 weeks | 5 days | Shorter total treatment duration than the
predicate is possible because of an
optimized and compressed treatment
schedule. |

Summary of Performance Data:

Sterilization and Shelf Life: The Magnus Neuromodulation System with SAINT Technology is not provided as a sterile device and is not intended for sterilization by the user. The shelf life and/or useful life of the hardware components are as indicated in their respective labeling and instructions for use. Software components will have updates managed as appropriate by Magnus Medical or its suppliers and therefore do not have a defined useful life at this time. Biocompatibility: Patient contact materials that are part of the Magnus Neuromodulation System were tested and are compliant with ISO 10993-1, Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process. Software for the Magnus Neuromodulation System with SAINT Software: Technology was designed and developed in accordance with current FDA guidance and industry standards including IEC 62304, Medical Device Software – Software lifecycle processes and ISO 14971, Application of risk management to medical devices. Hardware: The hardware components of the Magnus Neuromodulation System have undergone all applicable electrical safety, electromagnetic compatibility, performance, and usability testing required.

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Clinical: Clinical testing was performed to provide assurance of safety and effectiveness of the Magnus Neuromodulation System with SAINT Technology. The system was evaluated in four clinical studies, three open-label and one randomized and sham controlled. Data from these studies are summarized in the following tables:

| Title of Study | Number of
Participants | Summary of Results |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| High-dose Spaced theta-burst TMS
as a Rapid-acting Antidepressant in
Highly Refractory Depression1 | 6 | 5/6 (83.3%) responded (≥50% decrease in Hamilton
Depression Rating Scale (HDRS-17) and 4/6 remitted
(HDRS4 Williams NR, Sudheimer KD, Bentzley BS, et al., High-dose spaced theta-burst TMS as a rapid-acting antidepressant in highly refractory depression. Brain 2018;141:1-5.

2 Cole EJ, Stimpson KH, Bentzley BS, at al., Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment Resistant Depression. Am J Psychiatry 2020;177:716-726.

4 Note that MINT, SNT, and SAINT all refer to the same combination of target identification and treatment delivery that is SAINT Technology.

5 Blumberger DM et al. Effectiveness of theta burst vs. high-frequency repeitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomized non-inferiority trial. Lancet 2018;391:1683-92.

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populations and the outcomes for SAINT trials, both open-label and randomized controlled trials, demonstrate equivalent effectiveness as compared to the results from the THREE-D trial without introduction of any new safety concerns.

SAINT Technology Compared to the Predicate iTBS (THREE-D)	Study #1	Study #2	Study #3	Study #4	THREE-D*
# of Subjects	6	22 (21 per protocol)	29
(15 active/14 sham)	14	209 active
Baseline Characteristics
Age (mean)	56	45	49/52	52	42
Age (range)	38-69	19-78	27-73	23-82	18-65
Gender (% female)	67%	57%	34%	50%	59%
Maudsley Staging
Method Score (mean)	14	10	9/9	9.5	6.3
# having prior TMS	6	7 (only 1 previously
remitted)	0	-	0
# having prior ECT	6	0	0	-	16
# having prior VNS	1	0	0	-	0
MADRS at baseline
(mean)	40.3	34.86	31/35	32	-
HDRS at baseline
(mean)	16 (6-item)
28.8 (17-item)	13.9 (6-item)
25.9 (17-item)	14/15 (6-item)
24/26 (17-item)	12.5 (6-item)	23.7 (17-item)
Type of Study	Single arm,
Open label	Single arm
Open label	Randomized,
blinded	Single arm
Open label	Randomized,
Open label
Treatment Arms	Single, active	Single, active	2 arms - active
(n=14) vs.
sham (n=15)	Single, active	2 arms - 10 Hz
rTMS (n=205)
vs. iTBS
(n=209)
Treatment	5 days SAINT
iTBS	5 days SAINT
iTBS	5 days SAINT
iTBS vs. 5 days
sham SAINT	5 days SAINT
iTBS	4-6 weeks 10
Hz rTMS vs. 6
weeks iTBS
Outcome
Response
(MADRS reduction
≥50%)	83.3%
(assessed at end
of 5 days of
treatment)	90.5%
(assessed at end
of 5 days of
treatment)	85.7% active
vs. 26.7% sham
(assessed
during the
month after
treatment)	92.8%
(assessed
during the
week after
treatment)	-
Remission (MADRS
≤10)	83.3%
(assessed at end
of 5 days of
treatment)	90.5%
(assessed at end
of 5 days of
treatment for
the 21 per
protocol
subjects)	78.6% active
vs. 13.3% sham
(assessed
during the
month after
treatment)	78.6%
(assessed
during the
week after
treatment)	-
Response (HDRS
reduction ≥50%)	83.3%	86.4 %
(HDRS-17)	-	71.4% (HDRS-

                                      | 49% (HDRS-

```
                                |
```

Table 4: Summary of Demographic and Effectiveness Data for Clinical Studies Performed with SAINT Technology Compared to the Predicate iTBS (THREE-D)

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*The predicate device, Nexstim Navigated Brain Therapy (NBT) System 2, relied on the THREE-D Clinical Study data for clearance, via its own predicate (K173620).

Note: The clinical performance data for the Magnus Neuromodulation System (MNS) with SAINT Technology were obtained from a total of 70 patients enrolled in four clinical trials (one randomized double-blind, sham-controlled study and three open-label studies) conducted in close geographical proximity. As a result of studies being performed at a single site, generalizability to the broader United States population has not been evaluated.

Note: The Magnus Neuromodulation System (MNS) with SAINT Technology has been evaluated at four weeks post treatment in all four clinical trials. Effectiveness has not been established beyond the timepoints evaluated in the four clinical studies.

Note: Blinding Assessment Study #3

The adequacy of blinding utilized in the investigation was assessed by asking participants to guess their treatment allocation and to report their confidence in their guess (on a scale of 1 to 5) on the last day of treatment. This guess and confidence level were translated to a guess metric that ranged from 0 (participant had full confidence that he or she received the sham treatment) to 1 (participant had full confidence he or she received the active treatment). Twenty-three (23) participants provided guesses as to which treatment they received, and 19 indicated their confidence in their guess. One-way t tests indicated no significant differences from chance (chance guess metric=0.50) in the sham (mean guess metric=0.39, p=0.56) and active (mean guess metric=0.43, p=0.52) treatment groups. Because not all participants indicated their confidence in their guess, binomial tests were also used to determine whether the number of correct guesses exceeded chance. Binomial tests indicated no significant differences from chance in proportion of correct guesses in the sham (6 of 10 correct, p=0.38) and active (7 of 13 correct, p=0.50) treatment groups. Finally, linear regression analysis detected no relationship between the guess metric and the change in depression severity as indicated by magnitude of proportional change in MADRS scores (=0.11. p=0.66). Since only 19 of 29 participants completed both parts of the blinding assessment. uncertainty remains as to the adequacy of the blinding for the remainder of the study population.

Adverse events from the Study #3 active treatment arm and the open label study (Study #4) of SAINT are listed in Table 5 below along with the adverse events reported in the THREE-D iTBS Study. (Note that Study #1 and Study #2 are not shown in the table, because these universitybased studies did not formally tabulate non-serious adverse events; zero serious adverse events were observed in either study.) All the adverse events reported for SAINT are similar to those

12

reported for THREE-D iTBS in type and incidence with the exception that fatigue is reported more frequently with SAINT, likely because of the increased time spent in the clinic for the five days of SAINT treatment. Notably, rates of fatigue were the same for active and sham SAINT groups.

Event	Number participants reporting event (%)6
	SAINT n=14 (active arm
from Study #3)	SAINT n=14 (Study #4)	iTBS (THREE-D) n=209
Headache	8 (57%)	6 (43%)	136 (65%)
Nausea	-	-	14 (7%)
Dizziness	-	1 (7%)	18 (9%)
Unrelated medical
problem	-	5 (36%)	46 (22%)
Fatigue	8 (57%)	5 (36%)	16 (8%)
Insomnia	-	5 (36%)	10 (5%)
Anxiety or agitation	4 (29%)	2 (14%)	9 (4%)
Back or neck
pain/discomfort	7 (50%)	3 (21%)	6 (3%)
Unrelated accidents	-	1 (7%)	3 (1%)
Vomiting	-	-	1 (6 Shown here are outcomes from the active SAINT arm (Study #3), active SAINT (Study #4), and the iTBS arm from the THREE-D study.