Praxis Precision Medicines : April 2024 Corporate Presentation

CORPORATE OVERVIEW

April 2024

Forward-looking statements

This presentation may contain "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business, operations, and financial conditions, including but not limited to express or implied statements regarding the current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our development plans, our preclinical and clinical results and other future conditions. Any forward-looking statements in this presentation are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this presentation, including, without limitation, risks relating to: (i) the success and timing of our ongoing clinical trials, (ii) the success and timing of our product development activities and initiating clinical trials, (iii) the success and timing of our collaboration partners' product development activities, (iv) the timing of and our ability to obtain and maintain regulatory approval of any of our product candidates, (v) our plans to research, discover and develop additional product candidates, (vi) our ability to enter into collaborations for the development of new product candidates, (vii) our ability to establish manufacturing capabilities, and our collaboration partners' abilities to manufacture our product candidates and scale production, (viii) our ability to meet any specific milestones set forth herein, and (ix) the potential addressable market sizes for product candidates. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give no assurance that such expectations will prove to be correct. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements.

For further information regarding the risks, uncertainties and other factors that may cause differences between our expectations and actual results, you should review the "Risk Factors" section of our Annual Report on Form 10-K for the year ended December 31, 2023 to be filed and other filings with the Securities and Exchange Commission.

Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this presentation, we have not independently verified, and make no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source.

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Four pillars guide how we develop medicines

GENETICS

Focus on therapeutic

targets identified through

human genetics

TRANSLATIONAL

TOOLS

Translational tools validate

potential of target and

product candidate and can provide early proof of biology

EFFICIENT &

RIGOROUS

Efficient, rigorous clinical development paths to proof- of-concept in humans applying an agile way of working

PATIENT-GUIDED

Patient-guided development strategies to deliver on what

patients actually need

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Praxis is positioned to bring more innovation to patients

into

4 >$7B 4 2 2027

Assets in	Commercial	Readouts next	Discovery	Cash
clinical	opportunity	eighteen months	platforms to	runway
trials	across the		optimize drug
	portfolio		development

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Two platforms to generate optimized therapies for defined patient populations

CEREBRUM	Molecule	Indication	Mechanism
ulixacaltamide	Tremor	T-type calcium channel modulator
	Essential
SMALL MOLECULE PLATFORM	PRAX-628	Focal Onset	Sodium channel functional state
Cerebrum utilizes deep		Seizures	modulator for broad use
understanding of neuronal	PRAX-562	DEE Epilepsies	Sodium channel functional state
excitability and neuronal			modulator for pediatric use
networks and applies a series of	PRAX-020*	KCNT1 Epilepsy	KCNT1 specific inhibitor
computational and experimental
tools to develop orally available
precision therapies	PRAX-050	Not disclosed	Not disclosed

SOLIDUS	Molecule	Indication	Mechanism
elsunersen	SCN2A GoF	Gapmer ASO
ANTISENSE OLIGONUCLEOTIDE	PRAX-080+	PCDH19 Mosaic	Gapmer ASO
(ASO) PLATFORM
Solidus is an efficient, targeted		expression
PRAX-090+	SYNGAP1 LoF	Splice switching ASO
precision medicine discovery and
development engine for ASOs	PRAX-100+	SCN2A LoF	Splice switching ASO
anchored on proprietary,
computational methodology

*PRAX-020 (KCNT1) is a research collaboration with UCB	5
+PRAX-080 (PCDH19 ), PRAX-090 (SYNGAP1) & PRAX-100(SCN2A-LoF) ASOs are a collaboration with The Florey Institute of Neuroscience and Mental Health

Four clinical stage assets and multitude of early-stage programs

PLATFORM

PRECLINICAL

PHASE ONE

PHASE TWO

PHASE THREE

UPCOMING MILESTONES

CEREBRUM

SMALL MOLECULE

PLATFORM

SOLIDUS

ASO PLATFORM

PRAX-020*

KCNT1

PRAX-050

Undisclosed

PRAX-090+

SYNGAP1

PRAX-080+

PCDH19

PRAX-100+

SCN2A LoF

Ulixacaltamide

Essential Tremor

PRAX-628

Focal Onset

Seizures

PRAX-562

DEEs

Elsunersen

SCN2A GoF DEE

Ulixacaltamide

• 1H: Complete enrollment
• 2H: Topline results

PRAX-628

• 2H: Initiate Phase 2 Focal Onset Seizures Study

PRAX-562

• Mid-year: Phase 2 EMBOLD Study topline Results

Elsunersen

• 1H: Regulatory alignment on registrational program

*PRAX-020 (KCNT1) is a research collaboration with UCB	6
+PRAX-080 (PCDH19 ), PRAX-090 (SYNGAP1) & PRAX-100(SCN2A-LoF) ASOs are a collaboration with The Florey Institute of Neuroscience and Mental Health

CEREBRUM

SMALL MOLECULE PLATFORM

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Ulixacaltamide

Milestones

1H 2024: Enrollment complete

2H 2024: Topline results

2025: File NDA

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Essential tremor market is significantly underserved and ready for disruption

7M	~2M		$4bn+
US Prevalence1	ET patients
seeking
	treatment		US ET Market

• Essential Tremor (ET) is the most prevalent movement disorder
• People with ET experience significant disruption of their daily activities
• Hallmark feature of ET is action tremor that primarily affects the hands2,3
• Almost all ET patients suffer from at least one comorbid condition (e.g., depression, anxiety, sleep disorders, cognitive dysfunction)4

Vast majority of the patients are left without any treatment option

• <30% of patients are eligible to receive propranolol due to other medications/health conditions
• Of those who start propranolol >50% discontinue after only 1 month
• Of those who start propranolol <20% still receive propranolol after 2 years

1. GHOSH (2016) (P.231, C.1, PH.1, L.1-2), 2. Elble RJ. Curr Neurol Neurosci Rep. 2013 Jun;13(6):353. 3. Putzke JD, et al. J Neurol Neurosurg Psychiatry. 2006 Nov;77(11):1235-7. 4. Vetterick, C., Lyons, K.E., Matthews, L.G. et
al. The Hidden Burden of Disease and Treatment Experiences of Patients with Essential Tremor: A Retrospective Claims Data Analysis. Adv Ther (2022). https://doi.org/10.1007/s12325-022-02318-8	9

Modified Activities of Daily Living 11 (mADL11) as Primary Endpoint

	11 items from the well-established
	TETRAS ADL scale
Each item is individually scored, up to a total of 33
0	= Slightly abnormal. Tremor is present but does not interfere with __.
1	= Mildly abnormal. Spills a little.
2	= Moderately abnormal. Spills a lot or changes strategy to complete task.
3	= Severely abnormal. Cannot drink from a glass or uses straw or sippy cup.
	Speaking	Dressing
	Using Keys	Hygiene
	Pouring	Working
	Writing	Drinking from a glass
	Feeding with a spoon

Carrying food trays, plates or similar items

Overall disability with most affected task

• Improvement based on regaining function
• Each point reduction provides benefit to a patient
• ADL assessment performed by a physician
• Aligned as primary endpoint for Essential3 studies with FDA

TETRAS = TRG Essential Tremor Rating Assessment Scale; ADL = Activities of Daily Living

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